用于生产丁烯基-多杀菌素杀虫剂的生物合成基因的制作方法

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专利名称:用于生产丁烯基-多杀菌素杀虫剂的生物合成基因的制作方法
发明概述本发明提供新的丁烯基-多杀菌素生物合成基因、整合这些生物合成基因的载体以及用这些生物合成基因转化的刺糖多胞菌(Saccharopolyspora)株系,同时还提供使用这些基因去提高多杀菌素样的大环内酯类杀虫剂的产量的方法和利用这些基因或其片段去改变产多杀菌素的刺糖多胞菌株系所产生的代谢产物。
背景技术
天然生产的多杀菌素化合物由与12员环的大环内酯相融合的5,6,5-三环系统、中性糖(鼠李糖)和氨基糖(forosamine)组成(见Kirst等人,1991)。如果这个氨基糖不存在,这些化合物被称作假糖苷配基。如果这个核心糖不存在,这些化合物则被称为反转的(reversepseudoaglycone)。A83543多杀菌素是由刺糖多胞菌NRRL18395菌株及其衍生物所产生。A83543多杀菌素家族的已知成员以及产生它们的株系已经在美国专利NO.5,362,634;5,202,242;5,840,861;5,539,089以及5,767,253上公开了。这些化合物以字母命名,多杀菌素A、B等。A83543多杀菌素A的结构在表1中给出。这些A83543多杀菌素化合物能够有效的控制蜘蛛类动物、线虫动物和昆虫[尤其是鳞翅目(Lepidoptera)和双翅目(Diptera)种类]。它们有着良好的环境和毒理学性质。编码指导A83543多杀菌素生物合成的酶的DNA序列已经在美国专利NO.6,143,526中被公开。这些克隆基因和开放阅读框被命名为spnA、spnB、spnC、spnD、spnE、spnF、spnG、spnH、spnI、spnJ、spnK、spnL、spnM、spnN、spnO、spnP、spnQ、spnR、spnS、刺糖多胞菌gtt、刺糖多胞菌gdh、刺糖多胞菌epi和刺糖多胞菌kre。除了鼠李糖生物合成的基因之外,这些多杀菌素生物合成基因,特别是spnA、spnB、spnC、spnD、spnE、spnF、spnG、spnH、spnI、spnJ、spnK、spnL、spnM、spnN、spnO、spnP、spnQ、spnR和spnS连续地排列在刺糖多胞菌染色体上大约74Kb的区域内。spnA、spnB、spnC、spnD和spnE等基因同负责聚酮化合物生物合成的基因具有相似性,若阻断spnA、spnD或spnE,则不能产生任何多杀菌素产物。A83543多杀菌素合成也涉及到这个内酯核的桥连-在大环内酯产生者中很少见的活性。spnF、spnJ、spnL和spnM基因被认为参与这个生物合成步骤。据报道,spnG、spnH、spnI和spnK基因参与鼠李糖的添加和修饰。而spnN、spnO、spnP、spnQ、spnR和spnS基因则参与forosamine糖的生物合成和添加。负责鼠李糖生物合成的那些基因并不是连续地分布在A83543多杀菌素生物合成基因其它位置上。刺糖多胞菌gtt和刺糖多胞菌kre在一个不同的片段上被克隆,而刺糖多胞菌gdh和刺糖多胞菌。epi则在其它不同片段上被克隆。最近一种新的生物体-刺糖多胞菌LW107129(NRRL30141)及其衍生菌所产生的另一种多杀菌素-丁烯基-多杀菌素在美国专利申请NO.09/661,065(与WO 01/19840相应)和美国专利申请NO.60/277,601上被公开。在上述申请中有40多个该化合物家族的成员被定义。刺糖多胞菌LW107129(NRRL30141)产生的这种丁烯基-多杀菌素化合物同A83543多杀菌素系列中的化合物不同。这两类多杀菌素之间的主要区别是连在大环上C-21位置处的碳链取代物不同。天然的丁烯基-多杀菌素在C-21位置处被3-4个碳的碳链取代,优选为丁烯基,而天然的A83543多杀菌素在C-21位置处被1-2个碳的碳链取代,优选为乙基。这些丁烯基-多杀菌素化合物用作反应物生产合成修饰的多杀菌素类化合物,后者在2001年3月21日提交的美国临时专利申请60/277,546“21-丁烯基及相关的多杀菌素的合成衍生物”中所公开。而优选,这些化合物及其合成衍生物用于控制蜘蛛类、线虫类以及昆虫[尤其是鳞翅目和双翅目种类]。除了C-21上的丁烯基之外,丁烯基-多杀菌素同A83543多杀菌素系列相比还呈现出许多其它差异。表1总结了这些丁烯基-多杀菌素化合物的亚分类以及说明同A83543多杀菌素的不同之处的因素。表1给出了这些丁烯基-多杀菌素的命名,并且根据它们结构首字母缩写词称为“for-rham-I”,“for-rham-II”“for-rham-III”及其衍生物。在这些情况下,I、II和III指代被适当取代的大环内酯结构(IR4=R5=H;IIR5=CH3,R4=H或OH;IIIR5=H,R4=OH),“for”代表C-17位置上的糖(for=forosamine),而“rham”代表C-9位置上的糖(rham=3-O-甲基鼠李糖)。NRRL30141菌株产生的第二种大环内酯结构,具有通式(2),显示有14员环大环内酯环,在下文中被称作IV,而完全糖基化的化合物则被称为“for-rham-V。”式(1)和(2)的丁烯基-多杀菌素化合物用于治理蜘蛛类、线虫类和昆虫[尤其是鳞翅目和双翅目种类],它们对环境无害而且具有吸引人的毒理性质。这些差别包括C-21位上的广泛修饰、C-8位上的羟基化和其他的糖,包括中性糖在C-17位上被forosamine所取代。另外,具有与14员环大环稠合的5,6,5-三轮环系统,在C-17和C-9上各自连有forosamine和鼠李糖的化合物曾公开于上述专利申请中。
表1
*R3是具有下列(3a)-(3c)式之一的基团。
**R9是具有(9a)-(9i)式之一的基团。
表1中的化合物1-21由刺糖多胞菌LW107129(NRRL30141)产生,并已在美国专利申请09/661,065(相应于WO01/19840)中公开,32和33号化合物则已公开于2001年3月21日提交的美国临时专利申请60/277,601“大环内酯类杀虫剂”中。尽管丁烯基-多杀菌素同A83543多杀菌素的结构存在差异,但可以推断出,它们的某些生物合成基因是相似的。但是,正如上面所详细论述的那样,刺糖多胞菌LW107129(NRRL30141)能够产生大量独特的丁烯基-多杀菌素因子和化合物,而这些在A83543多杀菌素中并未观察到。因此,这种生物也必须具有与刺糖多胞菌中的A83543多杀菌素生物合成酶不同的新的生物合成酶。特别是,相对于A83543多杀菌素来说,刺糖多胞菌LW107129(NRRL30141)的丁烯基-多杀菌素生物合成酶一定能通过2个碳原子(在C-21上连接丁烯基而不是乙基)来延伸聚酮化合物链。它们在C-17上必须能合成并连接上另外的氨基糖或中性糖,并且要在C-8和C-24位上发生羟基化。另外,相对于刺糖多胞菌,在刺糖多胞菌LW107129(NRRL30141)中发生的鼠李糖甲基化是不同的。在A83543多杀菌素上显示出鼠李糖甲基化特征改变的刺糖多胞菌阻断突变体(如美国专利5,202,242和5,840,861所公开)能够产生典型的A83543多杀菌素的单去甲基的(mono-desmethylated)鼠李糖衍生物。只有在西萘芬净这样的甲基化酶抑制剂存在时,才能观察到A83543多杀菌素的双去甲基(di-desmethyl)鼠李糖衍生物。甲基化酶抑制剂不存在时,鼠李糖甲基化改变的刺糖多胞菌LW107129(NRRL30141)突变体能够产生大量的丁烯基-多杀菌素双去甲基和三去甲基鼠李糖衍生物。生产丁烯基-多杀菌素的一大障碍就是生产极少量的丁烯基-多杀菌素即需要很大的发酵体积。含有一或多个丁烯基-多杀菌素生物合成酶的基因的DNA克隆片段可复制基因来提高产率。通过能将大菌素转变成泰乐菌素的限制速度的甲基化转移酶的编码基因(Baltz等,1997)以及复制gtt和gdh基因(Baltz等,2000)可以分别在链霉菌属弗氏链霉菌(Streptomyces fradiae)和刺糖多胞菌的发酵物中提高这类化合物的产率。克隆的丁烯基-多杀菌素生物合成基因也提供了生产具有不同杀虫剂活性谱的丁烯基-多杀菌素新衍生物的方法。采用重组DNA技术构建的刺糖多胞菌LW107129(NRRL30141)突变株(其中某些丁烯基-多杀菌素生物合成酶的编码基因已被阻断)能够合成特殊的中间物(或它们的天然衍生物)。利用这个策略可以有效地产生生产新的6-脱氧红霉素衍生物的红色糖多胞菌(Saccharopo1yspora erythraea)(Weber和McAlpine,1992)。丁烯基-多杀菌素生物合成基因在其它能够生产类似化合物的生物体,如刺糖多胞菌,中也能表达。以天然的丁烯基-多杀菌素启动子或异源启动子表达时这些基因产生兼有多杀菌素和丁烯基-多杀菌素独特结构性质的新杂合分子。刺糖多胞菌LW107129(NRRL30141)或刺糖多胞菌的突变株也能合成新的中间体,这些突变株中参与丁烯基-多杀菌素生物合成的酶的编码基因的某些部分被在体外特异性突变的相同基因片段或来自于其它生物的相应基因片段所取代。这个杂合基因将会产生功能已经改变(或者缺乏某种活性或者进行新的酶促转化)的蛋白质。在突变株的发酵产物中将产生新的化学物质。利用这样的方法可构建能够产生新的脱水红霉素衍生物的红色糖多胞菌菌株(Donadio等,1993)。丁烯基-多杀菌素的生物合成通过逐步缩合和修饰二碳和三碳羧酸前体,产生线性聚酮化合物来进行(

图1A),这个聚酮化合物经环化和桥连可生成四环糖苷配基(图1B)。接下来形成假糖苷配基(含有三-氧-甲基化的鼠李糖),然后将二-氮-甲基化forosamine或者其他糖加上去完成这个生物合成过程(图1B)。其它的大环内酯类化合物,如抗生素红霉素、抗寄生虫的除虫霉素和免疫抑制剂纳巴霉素,都以相似的方式合成。在产生这些化合物的细菌中,抗生素是由I型聚酮化合物合成酶(PKS)中的几种大型且多功能的蛋白质催化而成(Donadio等,1991;Ikeda等,1999;Schwecke等,1995)。这些多肽形成由一个起始模块和几个延伸模块所组成的复合体。其中每一个都向正在增长的聚酮化合物链上增加一个特异性的乙酰CoA前体并以特异的方式去修饰这个β-酮基基团(图1A)。因此,聚酮化合物的结构由PKS中模块的组成和次序所决定的。模块包含多个结构域,而每个结构域执行特定的功能。起始区模块含有酰基转移酶(AT)结构域,用于从前体向酰基载体蛋白(ACP)结构域添加酰基基团。这个起始区模块也可能含有KSQ结构域,此结构域同β-酮基合成酶(KS)结构域高度相似,但其上活性位点的半胱氨酸被谷氨酰胺所取代(Bisang等,1999),因此,KSQ不再具有缩合活性。KSQ结构域保留脱羧酶活性并决定起始模块的前体特异性。延伸模块含有AT和ACP结构域以及完整的β-酮基合成酶(KS)结构域,后者通过脱羧缩合向已经存在的聚酮化合物链上增加新的酰基-ACP。其它的结构域也可能存在于每个延伸模块中以完成特定的β-酮基修饰β-酮基还原酶(KR)结构域将β-酮基还原为羟基,脱水酶(DH)结构域去除羟基并留下双键,以及烯脂酰还原酶(ER)结构域还原上述双键并留下饱和碳。最后的延伸模块以硫酯酶(TE)结构域终止。此结构域以大环内酯形式从PKS上释放这个聚酮化合物。聚酮化合物合成酶主要由3-7个大的开放阅读框所编码(Donadio等,1991;Ikeda等,1999;Schwecke等,1995)。特异功能性聚酮化合物合成酶的组装要求这些蛋白质之间特异性蛋白质-蛋白质相互作用。活化的大环内酯类抗生素由大环内酯经另外的修饰(如甲基化和还原状态的改变以及添加不寻常的糖)衍生而来。修饰、糖的合成与连接所需的大部分基因均聚集在PKS基因周围。在大环内酯类抗生素,如红霉素和泰乐霉素(Donadio等,1993;Merson-Davies和Cundliffe,1994)和胞外多糖,如沙门氏菌(Salmonella)和耶尔森氏菌(Yersinia)的O-抗原(Jiang等,1991;Trefzer等,1999)的产生者中,编码脱氧糖生物合成酶的基因是相似的。所有这些合成都涉及通过添加核苷二磷酸然后脱水,还原和/或差向立体异构化来活化葡萄糖。产生的脱氧糖可能会接受一或更多其它修饰,如脱氧、转氨和甲基化作用。然后这些糖被特异性糖基化转移酶的作用整合到大环内酯上。参与糖的合成和附着的基因可能紧密地聚集在一起-甚至作为单个的操纵子被转录-或者它们可能会被分散在不同位置(Ikeda等,1999;Shen等,2000;Aguirrzabalaga等,1998)。这里所使用的术语定义如下a.a.-氨基酸。AmR-阿泊拉霉素抗性赋予基因。ACP-酰基载体蛋白结构域。AT-酰基转移酶结构域。阻断突变株-突变株,其突变阻断生物合成路径的特异的酶功能从而产生前体或别的(shunt)产物。bp-碱基对。bus-丁烯基-多杀菌素生物合成基因。丁烯基-多杀菌素-结构上同A83543多杀菌素(表1)不同的一类发酵产物,在美国申请专利NO.091661,065和临时的美国申请专利NO.60/277,601中已公开。或者是一种由利用全部或大部分丁烯基-多杀菌素基因的微生物所产生的一种类似大环内酯的发酵产物。丁烯基-多杀菌素基因-编码丁烯基-多杀菌素生物合成所需产品的DNA序列,特别是下文中所描述的基因busA、busB、busC、busD、busE、busF、busG、busH、busI、busJ、busK、busL、busM、busN、busO、busP、busQ、busR和busS,或者它们的功能等价物。克隆-将DNA片段整合到重组DNA克隆载体并用这个重组DNA转化宿主细胞的过程。密码偏倚性-使用特异密码子去针对特异的氨基酸的倾向性。对于刺糖多胞菌LW107129(NRRL30141)而言,这种倾向性指使用第三个碱基是胞嘧啶或鸟嘌呤的密码子。互补-用克隆的基因使突变菌株恢复正常表型。接合-遗传物质从一个细菌细胞转移到另一个细胞的过程。cos-噬菌体λ的粘性末端序列。粘粒-重组DNA克隆载体,其为不仅能在宿主细胞内以与质粒相同的方式复制,还能包装进噬菌体头部的质粒。DH-脱水酶结构域ER-烯酯酰还原酶结构域基因-编码多肽的DNA序列基因组文库-其中克隆有实质上代表特定生物体中全部DNA序列的DNA片段的一套重组DNA克隆载体。同源性-序列之间的相似性程度杂交-两个单链DNA分子退火形成双链DNA分子的过程,碱基可能完全也可能不完全配对。体外包装-DNA经体外包装在衣壳蛋白内形成病毒样的颗粒,该颗粒能够通过感染的方式将其中的DNA引入宿主细胞中。Kb-一千碱基对KR-β-酮基还原酶结构域KS-β-酮基合成酶结构域突变形成-在DNA序列上产生变化。它们在体内或体外随机或有目的地产生。突变可能是沉默的,也可能会导致翻译产物的氨基酸序列的改变,结果此产物蛋白的性质发生改变并形成突变表型。ORF-开放阅读框ori-质粒上复制(oriR)或转移(oriT)的起始点。%同源性-比较两个序列时,由BLAST程序所给出的同源性百分比。%相似性-比较两个序列时,由BLAST程序所给出的相似性百分比。PCR-聚合酶链式反应-特异扩增DNA某一区域的方法。PKS-聚酮化合物合成酶启动子-指导转录起始的DNA序列。重组DNA克隆载体-任何能够自主复制或整合的工具,包括但并不限于质粒,一个或更多其它DNA分子能够被或已经被加到载体自身含有的DNA分子上。重组DNA方法-用于创造、鉴定并修饰已克隆到重组DNA载体上的DNA片段的方法。限制性片段--由一或多个限制性酶作用产生的线性DNA分子。多杀菌素-也被称为A83543的发酵产物,或者由微生物利用全部或大部分A83543多杀菌素基因产生的类似A83543的大环内酯发酵产物。其典型分子特征为由5,6,5三环与12元的大环内酯环融合构成的稠环结构,在21碳原子位置上连有一个1~2个碳原子的碳链,同时其分子骨架上还连有一个中性糖(鼠李糖)和一个氨基糖(forosamine)。多杀菌素基因--编码A83543生物合成所需产物的DNA序列。具体基因为spnA、spnB、spnC、spnD、spnE、spnF、spnG、spnH、spnI、spnJ、spnK、spnL、spnM、spnN、spnO、spnP、spnQ、spnR、spnS、刺糖多胞菌gtt,刺糖多胞菌gdh、刺糖多胞菌epi、和刺糖多胞菌kre及其功能等价物(如下文描述)。spn为A83543生物合成基因。亚克隆为带有插入DNA的克隆载体,该DNA来自于另一个与之大小相同或大于它的DNA。TE为硫酯酶结构域。转结合子为通过接合作用形成的重组菌株。
附图简述图1中1A和1B阐明丁烯基-多杀菌基生物合成的示意图。图2阐明HindII、EcoRV、和ScaI片段及开放阅读框在刺糖多胞菌LW107129(NRRL30141)的被克隆区中的排列顺序。图3是粘粒Cosmid pOJ436的功能图及限制性位点。图4阐明17-(4”-O-甲基夹竹桃糖)-丁烯基-多杀菌素[图1中的化合物(11)]的生物合成途径。
发明简述本发明克隆了丁烯基-多杀菌素的生物合成基因和相关的ORFs,并测定了它们的DNA序列。它们在下文中分别指busA、busB、busC、busD、busE、busF、busG、busH、busI、busJ、busK、busL、busM、busN、busO、busP、busQ、busR、busS和ORF LI、ORF LII、ORF LIII、ORF LIV、ORF LVI、ORF LVII、ORF LVIII、ORF LIX、ORF RI、ORF RII和ORF RIII等基因。图1和下文的讨论证实了这些克隆基因在多杀菌素生物合成中的功能。一方面,本发明提供含有编码丁烯基-多杀菌素生物合成酶DNA序列的分离的DNA分子。该酶的氨基酸序列由选自于SEQ ID NO3-7和8-29所定义,或者由其中一或几个氨基酸发生替换而不改变所编码酶功能的上述氨基酸序列所决定。在优选的实施方案中,该DNA序列选自busA、busB、busC、busD、busE、ORF RI、ORF RII、ORF RIII、busF、busG、busH、busI、busJ、busK、busL、busM、busN、busO、busP、busQ、busR、busS、ORF LI、ORF LII、ORF LIII、ORF LIV、ORF LVI、ORF LVII、ORF LVIII和ORF LIX等基因,所述基因分别由SEQ ID NO1中的碱基1-13032、13059-19505、19553-29053、29092-43890、43945-60636、62090-63937、65229-66602、68762-69676,和SEQ ID NO2中的碱基114-938、1389-2558、2601-3350、3362-4546、4684-6300、6317-7507、7555-8403、8640-9569、9671-10666、10678-12135、12867-14177、14627-15967、16008-17141、17168-17914、18523-19932、19982-20488、20539-21033、21179-21922、22674-23453、23690-24886、26180-26923、27646-28473所描述。另一方面,本发明提供含有编码丁烯基-多杀菌素PKS结构域的DNA序列的分离的DNA分子。该结构域选自KSi、ATi、ACPi、KSb、ATb、KRb、DHb、ACPb、KS1、AT1、KR1和ACP1等结构域。这些结构域各自由SEQ ID NO3的氨基酸6-423、528-853、895-977、998-1413、1495-1836、1846-2028、2306-2158、2621-2710、2735-3160、3241-3604、3907-4086和4181-4262所描述。在优选的实施方案中,该DNA序列选自SEQ ID NO1中的碱基16-1269、1582-2559、2683-2931、2992-4239、4483-5508、5538-6084、6916-7554、7861-8130、8203-9480、9721-10812、11719-12258和12541-12786。另一方面,本发明提供含有编码多杀菌素PKS结构域的DNA序列的分离的DNA分子。该结构域选自KS2、AT2、DH2、ER2、KR2和ACP2,而这些结构域各自由SEQ ID NO4的氨基酸1-421、534-964、990-1075、1336-1681、1685-1864和1953-2031所描述。在优选的实施方案中,该DNA序列选自SEQ ID NO1中的碱基13059-14321、14658-15900、16026-16283、17064-18100、18111-18650和18915-19151。另一方面,本发明提供含有编码多杀菌素PKS结构域的DNA序列的分离的DNA分子。该结构域选自KS3、AT3、KR3、ACP3、KS4、AT4、KR4和ACP4,而这些结构域各自由SEQ ID NO5的氨基酸1-421、528-814、1157-1335、1422-1503、1526-1949、2063-2393、2697-2877、2969-3049所描述。在优选的实施方案中,该DNA序列选自SEQ ID NO1中的碱基19553-20815、21143-22000、23021-23557、23816-24061、24128-25399、25739-26731、27641-28183和28457-28699。另一方面,本发明提供含有编码多杀菌素PKS结构域的DNA序列的分离的DNA分子。该结构域选自KS5、AT5、DH5、KR5、ACP5、KS6、AT6、KR6、ACP6、KS7、AT7、KR7和ACP7,而这些结构域各自由SEQ IDNO6的氨基酸1-422、537-864、891-1076、1382-1563、1643-1724、1746-2170、2281-2611、2914-3093、3186-3267、3289-3711、3823-4151、4342-4636和4723-4804所描述。在优选的实施方案中,该DNA序列选自SEQ ID NO1中的碱基29092-30357、30700-31683、31762-32319、33235-33780、34018-34263、34327-35601、35932-36924、37831-38370、38647-38892、38956-40224、40560-41544、42115-42999和43258-43503。另一方面,本发明提供含有编码多杀菌素PKS结构域的DNA序列的分离的DNA分子。该结构域选自KS8、AT8、DH8、KR8、ACP8、KS9、AT9、DH9、KR9、ACP9、KS10、AT10、DH10、KR10、ACP10和TE10,而这些结构域各自由SEQ ID NO7的氨基酸1-424、530-848、885-1072、1371-1554、1650-1728、1751-2175、2289-2616、2642-2775、3131-3315、3396-3474、3508-3921、4036-4366、4389-4569、4876-5054、5148-5229和5278-5531所描述。在优选的实施方案中,该DNA序列选自SEQ ID NO1中的碱基43945-45216、45532-46488、46597-47160、48055-48606、48892-49083、49195-50469、50809-51792、51868-52269、53335-53889、54130-54366、54466-55707、56050-57042、57109-57651、58570-59106、59386-59631和59776-60537。另一方面,本发明提供含有编码多杀菌素PKS模块的DNA序列的分离的DNA分子。该模块选自SEQ ID NO3中的碱基6-997、SEQ IDNO3中的碱基998-2710、SEQ ID NO3中的碱基2735-4262、SEQ ID NO4中的碱基1-2031、SEQ ID NO5中的碱基1-1503、SEQ ID NO5中的碱基1526-3049、SEQ ID NO6中的碱基1-1724、SEQ ID NO6中的碱基1746-3267、SEQ ID NO6中的碱基3289-4804、SEQ ID NO7中的碱基1-1728、SEQ ID NO7中的碱基1751-3474、SEQ ID NO7中的碱基3508-5531。在优选的实施方案中,该DNA序列选自SEQ ID NO1中的碱基16-2931、2992-8130、8203-12786、13059-19151、19553-24061、24128-28699、29092-34263、34327-38892、38956-43503、43945-49083、49195-54366和54466-60537。另一方面,本发明提供重组DNA载体,其含有本发明上述的DNA序列。另一方面,本发明提供用本发明上述的重组载体转化的宿主细胞。另一方面,本发明提供提高多杀菌素生产菌生产多杀菌素能力的方法。具体步骤如下1)用重组DNA载体或其部分转化微生物,该微生物可借助生物合成途经生产丁烯基-多杀菌素或其前体。该载体或其部分含有本发明上述的DNA序列,该序列编码上述途经中限速酶活性的表达。
2)在适合于细胞的生长和分裂、适合上述DNA序列的表达以及多杀菌素产生的条件下,对用本发明的重组DNA载体转化的微生物进行培养。另一方面,本发明提供了生产多杀菌素的微生物,该微生物含有可操作的丁烯基-多杀菌素生物合成基因,其中busA、busB、busC、busD、busE、busF、busG、busH、busI、busJ、busK、busL、busM、busN、busO、busP、busQ、busR和busS这些基因中至少有一个被复制。另一方面,本发明提供了生产丁烯基-多杀菌素的微生物,该微生物在其基因组中含有丁烯基-多杀菌素生物合成基因。在这些基因中至少有一个被失活,剩下的基因可操作性产生那个失活基因的表达产物以外的丁烯基-多杀菌素。优选微生物是刺糖多胞菌LW107129(NRRL30141)或刺糖多胞菌突变菌株。更优选微生物是刺糖多胞菌LW107129(NRRL30141)的突变菌株。本发明也提供在正常情况下不产生丁烯基-多杀菌素的生物体中表达丁烯基-多杀菌素生物合成基因。这些基因可以在天然的bus基因的启动子或与受体菌兼容的异源启动子控制下表达。优选生物体能产生多杀菌素类化合物,更优选的微生物是刺糖多胞菌或其衍生物。本发明也提供了生产丁烯基-多杀菌素的微生物,其基因组中含有可操作的丁烯基-多杀菌素生物合成基因。其中所说的基因a)包含的PKS模块比SEQ ID NO1中存在的至少多一个或至少少一个;b)含有由于缺失、失活或增加KR、DH或ER结构域或由于替换AT结构域而与SEQ ID NO1中相应模块不同的PKS模块。优选的微生物是刺糖多胞菌LW107129(NRRL30141)突变菌株。本发明也提供通过培养本发明的新型微生物而产生的丁烯基-多杀菌素。另一方面,本发明提供分离丁烯基-多杀菌素生物合成基因的方法。该方法包括构建丁烯基-多杀菌素产生菌的基因组文库,并使用SEQID NO1或者SEQ ID NO2的至少二十个碱基的标记的核酸片断作为杂交探针。本领域的技术人员都应理解在要求保护的氨基酸序列上进行替代而在本质上不改变蛋白质的基本功能是可行的。因此,本发明也包括通过如此变异得到的氨基酸序列和相应编码变体的DNA序列。优选,氨基酸序列是那些本质上具有相同功能并且同天然的氨基酸序列有98%以上同一性的氨基酸序列。
发明详述作为丁烯基-多杀菌素基因使用和表征的先决条件,必须分离和鉴定编码涉及这一杀虫剂生物合成的相关酶基因。在随后的实施例1中描述的方法涉及基因组粘粒文库的构建和通过DNA杂交进行的后续筛选。
实施例1a.刺糖多胞菌LW107129(NRRL30141)细胞总DNA的分离刺糖多胞菌LW107129(NRRL30141)被接种于100mL生长培养基中(9.0g/L右旋糖,30g/L trypticase大豆汤,3.0g/L酵母提取物,2.0g/L MgSO4·7H2O)上述培养基被置于500mL锥形瓶中,30℃,150rpm振荡培养72小时;然后4℃,3000rpm离心10分钟以得到沉淀的细胞;去除上清液,沉淀用20mL TE缓冲液(10mM Tris/HCl,pH8.0;1mM EDTA,pH8.0)清洗,再以3000rpm离心,并将沉淀置于-20℃冻存。进行细胞总DNA分离时再把它解冻。刺糖多胞菌LW107129(NRRL30141)细胞总DNA利用基因组DNA纯化试剂盒(Qiagen Inc.,Valencia,CA)提取。来自于100mL培养物的冷冻沉淀细胞在11mL B1缓冲液(50 mM Tris/HCl,pH8.0;50mM EDTA,pH8.0;0.5%Tween 20,0.5%Triton X-100)中被重新悬浮,该缓冲液含有11μL Qiagen公司产的RNA酶A溶液(100mg/mL)。然后向这一悬液中加入300μL溶菌酶贮存液(100mg/mL;Sigma Chemical Co.,St.Louis,MO)和500μL蛋白酶K贮存液(50mg/mL;Sigma Chemical Co.),涡旋混合并在37℃温育30分钟,然后向细胞裂解物中加入4mLB2缓冲液(3M盐酸胍;20%Tween 20),在管中轻柔颠倒混合,然后该细菌裂解物在50℃温育30分钟,细菌裂解物中的总DNA利用Qiagen Genomic-tip 500/Gtips按照厂商的推荐使用说明提取出来。所得的纯化的DNA溶解在5mLTE缓冲液中并在4℃贮存。
b.基因组粘粒文库的构建从刺糖多胞菌LW107129(NRRL30141)分离出的细胞总DNA[按照Ausubel等编写的现代分子生物学实验方法(John Wiley and Sons,Inc.,New York,NY)3.1.3节所述操作]用Sau 3A I酶进行部分消化。利用小规模反应(80μL反应体系中含有40μg细胞总DNA)来选择合适的消化酶和细胞总DNA的比例,从而能够将部分消化的DNA片断最大程度集中在25~50Kb范围内。然后反应物在65℃加热15分钟以使Sau 3A I酶失去活性,用3%的琼脂糖电泳分析等分的反应物,来检测部分消化的DNA片断在所需范围内的相对丰度。一旦选择好合适的消化酶与细胞总DNA的比例,反应体系可加大以获得足够量的部分消化的细胞总DNA,该DNA片断在粘粒文库的构建中用作为插入的DNA片断。一般规模的反应是将400μg刺糖多胞菌LW107129(NRRL30141)细胞总DNA同9个单位的Sau3A I(Gibco BRL,Gaithersburg,MD)在1×的React4缓冲液中(厂商提供10×母液)以总体积800μl于37℃温育15分钟,然后65加热20分钟以使Sau 3A I酶失去活性,部分消化的细胞总DNA用相同体积已平衡的苯酚-氯仿(50∶50;v/v)溶液混合,轻柔颠倒使之充分混合,然后14000g离心15分钟,取出水相。用等体积的氯仿-异戊醇溶液(24∶1,v∶v)与水相混合,轻柔颠倒使两项混合,14000g离心15分钟,水相移至1个新管中并加入0.1体积3M乙酸钠(pH5.2),然后再加2倍体积冰冷的100%乙醇,轻柔颠倒使之混合,为了帮助DNA沉淀下来,样品要在-70℃过夜,DNA沉淀通过14000g离心20分钟而得到。DNA被重悬于50μL双蒸水中并在-20℃贮存。用于构建粘粒文库的载体为含用于筛选的阿泊拉霉素抗性基因的pOJ436(图3),为了最大程度避免粘粒载体DNA同自身的重新连接,在1.2mL总体积的1×SAP缓冲液(厂商提供10×母液)中将酶切过的DNA同20个单位的虾碱性磷酸酶(Roche/BoehringerMannheim,Indianapolis,IN)在37℃温育2小时,以使Bam HI酶切的POJ436 DNA发生去磷酸化作用,Sau 3A I消化的基因组DNA被连接到POJ436去磷酸化的Bam HI位点上,并用使部分消化的DNA与载体DNA为5∶1的比率。对于这个反应来说,插入序列同载体DNA在20单位T4 DNA连接酶(New England Biolabs Inc.,Beverly,MA)的作用下在1×的T4 DNA连接酶缓冲液(厂商提供10×母液)体系中16℃反应过夜。然后使用Gigapack III Gold Packaging Extract(Stratagene,La Jolla,CA)将连接混合物包装,使用大肠杆菌菌株DH5α-MRC+细胞(Gibco BRL)按照厂商的推荐使用说明对重组噬菌体进行滴度测量。将宿主细胞培养物和重组噬菌体的等份(20~40μL)涂布在含有100mg/L阿泊拉霉素(SigmaChemical Co.)的LB琼脂平板上(10g/L细菌-胰蛋白胨,10g/L氯化钠,5g/L细菌-酵母提取物,15g/L细菌琼脂;Difco实验室),37℃过夜培养。为了建立用于冻存的粘粒文库主平板,用无菌的牙签将单个克隆分别挑至无菌96孔板的每一孔中的微平板上[含250μL TB培养基(Terrific Broth)12g/L细菌-胰蛋白胨,24g/L Bacto-yeastextract,0.4%v/v甘油,17mM KH2PO4,72mM K2HPO4,100mg/L阿泊拉霉素]。并在37℃无振荡条件下过夜培养。为了从主平板产生复制平板,将96孔板复制器用于温育含250μL TB培养基(含100mg/L阿泊拉霉素)的无菌96孔微板,在37℃无振荡条件下过夜培养。无论是主平板还是复制平板,都要用多通道移液器向平板或培养物中加入7%(v/v)的二甲基亚砜溶液并混合,平板在-70℃贮存。确定要选择的重组粘粒插入基因的平均大小。首先利用NucleoSpin核酸纯化试剂盒(CLONTECH Laboratories,Inc.,PaloAlto,CA)分离出粘粒DNA,然后用20单位的限制性酶EcoRI(New EnglandBiolabs)37℃消化回收的DNA 1小时,在1.0%的琼脂糖凝胶电泳上分析限制性DNA片断,该DNA片断经0.5%溴化乙锭(Sigma Chemical Co.)染色后在紫外灯下即可看到。其相对大小可通过同1Kb的DNA梯(GibcoBRL)比较而得知。构建的粘粒文库的插入片段大小范围为20~40Kb。
C.筛选粘粒文库并鉴定含有丁烯基-多杀菌素物合成基因的粘粒用96孔板复制器接种每种大肠杆菌(E.coli)粘粒克隆的代表双份到Hybond N+(Amersham Pharmac ia Biotech,Piscataway,NJ)核酸结合膜上。将膜铺于含有100mg/L阿泊拉霉素的LB琼脂板上,于37℃温育过夜。按照厂商推荐方法处理膜。接种过的膜以菌落面向上置于用0.5N NaOH饱和的3MM滤纸(Whatman,Clifton,NJ)上1分钟,然后将其转到用变性液(1M Tris-HCl,PH7.6)饱和的第二张滤纸上1分钟使DNA变性。将滤膜转到已经在中和液(1M Tris-HCl,PH7.6/1.5M NaCl)中饱和的第三张滤纸上1分钟以中和该膜。最后在1MTris-HCl,pH7.6/1.5M NaCl的溶液中洗涤。用紫外交联装置(UV Stratalinker 1800,Stratagene)在1200μJ的条件下将DNA固定到膜上。用基于来自于刺糖多胞菌的spn基因制备的3个放射性标记的DNA探针去筛选上述已制备好的重组细菌文库(Baltz等,2000,表2)。利用聚合酶链式反应(PCR)技术,用寡核苷酸对去扩增spn生物合成基因簇的特异核酸序列。寡核苷酸引物在394 DNA/RNA合成仪(AppliedBiosystem/PekinElmer,Foster City,CA)上合成(见表2)。PCR反应遵照厂商推荐的方法,利用AmpliTaq_DNA聚合酶试剂盒(PekinElmer/Roche,Branchburg,NJ)进行。DNA片段扩增在48个样品的DNA热循环仪(Pekin Elmer Centus)中完成,循环条件如下1)94℃,1分钟;55℃,2分钟;72℃,3分钟;25个循环。2)72℃,10分钟;1个循环。通过0.1%琼脂糖凝胶电泳来检测扩增产物,而相应分子量的目的条带从凝胶上提取出来,遵循厂商推荐采用QiagenII凝胶提取试剂盒(Qiagen公司)进行。
表2 将上述膜置于65℃温育3小时,向300ml预杂交液中加入放射性标记探针,预杂交液成分组成为6×SSC(52.59g/L NaCl,24.66g/L柠檬酸钠,用10N NaOH将pH调到7.0),0.1%十二烷基磺酸钠(SDS),10×Denhardt氏液(50mg/L Ficoll[Type 400,Pharmacia],5.0mg/L聚乙烯吡咯烷酮,5.0mg/L牛血清白蛋白),100μg/L变性鲑鱼精。用于制备探针的DNA片段浓度都调到25ng,沸水浴变性10分钟。按照厂商推荐的随机引物法,用4μl High Prime反应混合物(Boehringer Mannheim)中,以50μCi[α32P]的dCTP(比活性3000Ci/mMol)随机引发标记。利用NucTrap Push Column(Stratagene)分离放射性标记的探针与未掺入的核苷酸。将探针于沸水加热10分钟变性,然后加到预杂交膜上。大约有2.0×107cpm探针被加到膜上来进行所有DNA杂交。所有探针杂交条件均为65℃,水浴振荡,16小时。将含有放射性标记探针spnF,spnS和spnE(TE)的杂交溶液倾倒在膜上。每组膜都要在中度严紧条件下清洗1)15分钟,室温,300ml3×SSC/0.5%SDS;2)30分钟,65℃,振荡,300ml新鲜的3×SSC/0.5%SDS;3)30分钟,室温,300ml 1×SSC/0.5%SDS。用来自于刺糖多胞菌LW107129(NRRL30141)粘粒9D3序列的放射性标记的探针进行膜筛选,在严紧条件下清洗1)30分钟,65℃,振荡,300ml新鲜的1×SSC/0.5%SDS洗液;2)30分钟,65℃,振荡,300ml新鲜的0.33×SSC/0.5%SDS洗液;3)30分钟,65℃,振荡,300ml新鲜的0.1×SSC/0.5%SDS溶液。使用手动控制的Geiger-Mueller计数机监测这些滤膜以确定背景同位素干扰是否最低。将膜置于3MM滤纸上并用塑料袋罩上,对X底片曝光。在冲洗前膜可在-70℃曝光24-72小时。通过限制性内切酶消化分析和粘粒载体的末端测序进一步鉴定推定的阳性粘粒克隆。使用NucleoSpin核酸纯化试剂盒(CLONTECHLaboratories,Inc.,Palo Alto,CA)分离粘粒DNA,并用20单位的限制酶EcoRI(New Enfland BioLabs)在37℃消化1小时。在1.0%琼脂糖凝胶中进行限制性DNA电泳。用溴化乙锭(EB)染色后,可以在紫外光下观察到DNA片段,其相对大小可通过与1KbDNA梯相比较而得知。另外,根据Burgett和Rosteck(1994)的方法,通过荧光循环测序法可以测知来自于粘粒/载体接头的刺糖多胞菌LW107129(NRRL30141)核苷酸序列。由3μl(2μg纯化的粘粒DNA)模板、1μl通用引物(4pmole)或反向引物(4pmole)、8μl Big Dye_反应混合器、1μlDMSO和7ml H2O构成的测序反应采用377ABIPrismTM测序仪(Applied Biosystem,Inc)在下述热循环条件下进行96℃,30秒;50℃,15秒;60℃,4分钟;25个循环。经鉴定,与刺糖多胞菌探针spnF,spnS和spnE(TE)阳性杂交的有8个粘粒克隆。粘粒8H3是与spnS和spnE(TE)探针都能杂交的两个克隆之一。粘粒9D3是仅与探针spnF杂交的三个克隆之一。粘粒10C1是仅与spnF探针杂交的3个克隆之一。来自粘粒9D3(SEQ ID NO1上的碱基297477-30163)粘粒/载体末端核苷酸测序结果的刺糖多胞菌LW107129(NRRL30141)序列的放射性标记的PCR片段与粘粒9F4杂交,由此从基因组文库鉴定出粘粒9F4。在粘粒9D3 DNA序列(SEQ ID NO39和SEQ ID NO40)的基础上合成出了两个引物。按照上面所描述的方法使用这些引物从刺糖多胞菌LWl07129(NRRL30141)基因组DNA扩增出416bp的DNA片段并用于杂交。通过对噬菌体M13(SeqWright,Houston,TX)中克隆的随机DNA片段进行荧光循环测序,可以测得粘粒8H3、9D3、9F4和10C1的完整序列。8H3和9D3的插入片段重叠,9D3和9F4的插入片段重叠,而9F4和10C1的插入片段重叠(见图2)。综合起来,这4个粘粒的插入片段跨越了特异序列上111个Kb(SEQ ID NO1和2)。SEQ ID NO.1包括busA的起始密码子及到其3’端的全部DNA(见图2)。SEQ ID NO.2开始自busA起始密码子之前的碱基并包括到这个碱基5’端的全部DNA。表3给出了SEQ ID NO.1和SEQ ID NO.2在这4个插入片段各自中的部分。
表3
图2给出了4个插入片段同110Kb序列之间的关系。
PKS基因SEQ ID NO.1包括一个大约60Kb的中心区域,此区域与编码已知的大环内酯生产者(Donadio等,1991;McDaniel和Katz,,2001;Dehoff等,1997)聚酮化合物合成酶的DNA具有显著的同源性。丁烯基-多杀菌素PKS DNA区域在ACP结构域末端包含5个与其它产大环内酯细菌的PKS开放阅读框(ORF)相似的带有框内终止密码子的开放阅读框(ORF)。这5个丁烯基-多杀菌素PKS基因呈首尾相对排列(见图2),而并不干涉非PKS区功能,例如在红霉素PKS基因AI和AII(Donadio等,1993)之间发现的插入成分。PKS基因被命名为busA,busB,busC,busD和busE。表4中给出了对应于5个多杀菌素PKS基因各自的核酸序列及其相应多肽表4 busA编码起始区模块(SEQ ID NO1上的碱基1-2931),延伸区模块b(SEQ ID NO1上的碱基2992-8130)和延伸区模块1(SEQ ID NO1上的碱基8205-13032)。表5给出了在起始区模块和延伸区模块b及1内的每一个功能结构域的核苷酸序列和相应氨基酸序列。
表5 busB编码延伸区模块2(SEQ ID NO1中的碱基13059-19505)。表6给出了在延伸区模块2范围内每一个功能结构域的核苷酸序列和相应氨基酸序列表6 busC编码延伸区模块3(SEQID NO1中的碱基19553-24061)和延伸区模块4(SEQID NO1中的碱基24128-29053)。表7给出了在延伸区模块3和4范围内每一个功能结构域的核酸序列和相应氨基酸序列表7 busD编码延伸区模块5(SEQ ID NO1中的碱基29092-34263),延伸区模块6(SEQ ID NO1中的碱基34327-38892)和延伸区模块7(SEQ ID NO1中的碱基38956-43503)。表8给出了在延伸区模块5、6和7范围内每一个功能结构域的核酸序列和相应氨基酸序列表8 spnE编码延伸区模块8(SEQ ID NO1中的碱基43945-49083),延伸区模块9(SEQ ID NO1中的碱基49195-54366)和延伸区模块10(SEQ ID NO1中的碱基54466-60707)。表9给出了在延伸区模块8、9和10范围内每一个功能结构域的核酸序列和相应氨基酸序列
表9 基于同其它聚酮合成酶结构域上保守氨基酸序列的相似性,在上述的表7-11中所鉴定的55个结构域的界限和功能根据同其他聚酮化合物合成酶预测,尤其是红霉素聚酮合成酶中的保守氨基酸的相似性,(Donadio等,1992)。与A83543多杀菌素PKS相同,busPKS在起始区模块的氨基酸末端有一个KSQ结构域。此结构域不能作为β-酮基合成酶发挥作用,因为在第172个氨基酸处,它包含谷氨酸残基,代替了β-酮基合成酶活性所需的半胱氨酸(Siggard-Andersen,1993)。据报道,具有使丙二酰-ACP脱羧功能的KSQ结构域是链的起始因子(Bisang等,1999)。其它的丁烯基-多杀菌素PKS结构域也具有功能。它们当中没有一个具有在红霉素和雷怕霉素PKS基因中发现的无活性结构域的序列特征(Donadio等,1991;Aparicio等,1996)。尽管在大小上busB-E同spnB-E相当,但busA仍然比spnA大5,244bp。前者开头的4245bp和末尾的3,486bp同后者有很高的相似性。但是,碱基4246-9548与spnA基因没有对应部分。这5Kb的区域编码的是另一个带有5个功能结构域的模块KSb,ATb,DHb,KRb和ACPb。这些区域与上述起始结构域一起共同负责生物合成丁烯基侧链,这是丁烯基-多杀菌素相对于A83543多杀菌素的特征基团。克隆的bus PKS基因busB、busC、busD和busE显示与A83543多杀菌素PKS基因spnB、spnC、spnD和spnE的相似性(表10)(Baltz等,2000)。
表10
*与刺糖多胞菌PKS基因和与bus和spn基因的其它类似结构域的相似性程度相当。在多杀菌素的生物合成过程中进行相似反应的蛋白质具有87-93%的氨基酸同一性而基因具有93-94%的DNA序列同一性。应该注意到,spn PKS酶SpnB-E与相似的busPKS酶必须维持底物特异性,因为尽管这些酶所完成的反应相同,但聚酮化合物底物不同。另外,5个PKS酶聚集成1个PKS需要特异的蛋白质-蛋白质相互作用。参与这种亚基间分子识别的残基是未知的,可能并不是刺糖多胞菌和刺糖多胞菌LW107129(NRRL30141)中保守的残基。
与PKS的基因负责额外的修饰
在PKS基因(克隆于粘粒8H3中)的DNA上游区存在22个开放阅读框(ORF)。每一个都至少含有100个密码子,并且以ATG或GTG开始,以TAA,TAG或TGA结束。并且具有密码偏倚性,即其DNA含有高百分比的鸟嘌呤和胞嘧啶残基的生物体内的蛋白编码区将会有偏倚性(Bibb等,1984)。这22个开放阅读框(ORF)在图2中以图表的方式给出。根据将在下文中被讨论的证据,开放阅读框中的14个已经被认为是丁烯基-多杀菌素生物合成基因,分别命名为busF,、busG、busH、busI、busJ、busK、busL、busM、busN、busO、busP、busQ和busS(图2标记为从F~S)。下文表11中,这14个基因及在spnS基因下游发现的开放阅读框(粘粒8H3中ORF LI、ORF LII、ORF LIII、ORF LIV、ORFLVI、ORF LVII、ORF LVIII和ORF LIX)的相应的多肽氨基酸序列及DNA序列都已经鉴定,表11也给出了PKS基因的下游ORF RI、ORF RII、ORFRIII的DNA序列以及相应的氨基酸序列(在粘粒2C10中)。
表11
(C)指示序列表中所给出的互补链
为了指定表11所鉴定的多肽功能,本实验给出了4个明显证据1.同已知功能的序列的相似性。
2.同A83543多杀菌素生物合成基因的相似性。
3.阻断目标基因的实验结果。
4.生物转化实验的结果。将预测多肽的氨基酸序列同生物技术国家信息中心(NCBI,Washington,DC)资料库中保存的序列对比,使用BLAST运算法则来测定它们同已知蛋白的相关性,定期重复在NCBI资料库进行BLAST搜索,可以从新添加的类似物得到新的判断。表12给出了2001年2月18日来自于基本BLAST搜索的显著匹配蛋白表12
*BLAST分值越高,表示相似性越高(Altschul等,1990)。直接对比bus开放阅读框和A83543多杀菌素生物合成基因(登录号为AY007564)。它们的DNA和蛋白质序列的高度相似性暗示了这些基因在多杀菌素生物合成中可能行使相似的功能。表13给出了bus和spn基因的相似性比较。
表13 尽管一些bus基因同spn基因的DNA和氨基酸序列具有高度同G性,但是值得注意的是相比于A83543多杀菌素一些bus基因产物能够明显催化丁烯基-多杀菌素生物合成过程中不同的反应。这些差异体现在从刺糖多胞菌LW107129(NRRL30141)中分离得到的不同的丁烯基-多杀菌素化合物,所有已公开的天然多杀菌素在C-17位上都被forosamine或特异的forosamine异构体所取代(Kirst等,1992)。另一方面,丁烯基-多杀菌素在C-17位上也更宽范围的forosamine异构体以及象amicetose、O-甲基葡萄糖和O-甲基夹竹桃糖等中性糖所取代。这些相对A83543多杀菌素C-17位上糖基化的多样性要求能够催化糖基化反应的糖基转移酶以及能够生产糖的生物合成酶,这些糖可能是由位于bus基因附近或染色体其他位置上的特异的合成酶基因催化合成,或者也可能由列出的丁烯基-多杀菌素生物合成基因的其它底物特异性合成。Amicetose能够被bus基因蔟以外的基因产生,或者它也有可能是forosamine生物合成的中间产物(图4)。甲基夹竹桃糖可以作为forosamine生物合成的副产物被生成,也可由鼠李糖O-甲基转移酶(busH、busI和busK)合成。这个糖可从NDP-4-酮-2,6-脱氧-D-葡萄糖(forosamine生物合成的中间产物)合成而来。因此,由公开的基因和其它刺糖多胞菌LW107129(NRRL30141)基因对这一前体进行的酮还原作用和O-甲基化作用可以生物合成含甲基夹竹桃糖的多杀菌素衍生物(图4)。另外,在表13中列出的9个基因直接同丁烯基-多杀菌素糖苷配基或PSA基因(busF、busG、busH、busI、busJ、busK、busL、busM和busP)相互作用。这些基因的糖苷配基和PSA底物同A83543多杀菌素的糖苷配基和PSA有着明显的差异。因此,这些基因同表13中列出的与之相关的spn对应物有着明显不同的底物特异性。几个由刺糖多胞菌LW107129(NRRL30141)产生的丁烯基-多杀菌素类似物在C-8或C-24位上被羟基化(表2)。与红霉素生物合成中在C-6位上进行羟基化相同,大环内酯类化合物也能由P-450单加氧酶催化作用下在合成后进行羟基化(Weber和McAlpine,1992)。ORF LVII同P-450单加氧酶有着很高的相似性,丁烯基-多杀菌素C-8或C-24位上的羟基化可能是由ORFLVII或刺糖多胞菌LW107129(NRRL30141)染色体其它位置编码的单加氧酶负责。另外,和白霉素一样,羟基化的前体,如甘醇酸酯和甘油,可在聚酮化合物合成过程中被整合进去(Omura等,1983)。据报道,在尼达霉素产生菌(nid AT6)中,专门负责添加甘醇酸酯的AT结构域同红霉素和雷怕霉素PKS基因中甲基-丙二酰辅酶A特异的AT结构域相似(Katz等,2000)。PKS模块7负责丁烯基-多杀菌素上C-8和C-9的添加。然而busAT7结构域中并没有同nidAT6完全相同的甲基-丙二酰辅酶A特异序列。相对于其它AT结构域和nidAT6来说,busAT7中存在着负责甘醇酸酯特异性的独特序列。与A83543多杀菌素相比,负责这些修饰的丁烯基-多杀菌素生物合成基因是独一无二的,因为刺糖多胞菌不能产生这样的羟基化的多杀菌素。另外,相对于刺糖多胞菌,刺糖多胞菌LW107129(NRRL30141)中的鼠李糖甲基化的特异性被改变了。在美国专利5,202,242和5,840,861中公开的刺糖多胞菌突变株显示出A83543多杀菌素鼠李糖上甲基化的变化,该突变株一般产生A83543多杀菌素的单去甲基化的鼠李糖衍生物,而其双去甲基鼠李糖衍生物只有在西萘芬净这样的甲基转移酶抑制剂存在时才能被检测到。在无甲基转移酶抑制剂的情况下,携有鼠李糖甲基化改变的基因的刺糖多胞菌LW107129(NRRL30141)突变株能够产生大量丁烯基-多杀菌素的双和三去甲基鼠李糖衍生物。作为补充性研究,将含有刺糖多胞菌LW107129(NRRL30141)bus DNA的粘粒结合其中丁烯基-多杀菌素生物合成发生改变的该菌株的突变株(详细资料见随后的实施例4),而后测试这一转化接合子将阻断突变体的产物转化为其它多杀菌素的能力。使用的突变株是30141.8,它产生3’-O-去甲基鼠李糖-丁烯基-多杀菌素(3-ODM)和相关的化合物,而30141.8/8H3转化接合子产生丁烯基-多杀菌素而不是3-ODM,所以,负责鼠李糖3’位置处甲基化的基因应位于粘粒8H3中。在目标基因破坏实验中,通过PCR从粘粒DNA中扩增内部片段进而将其克隆进质粒。然后将质粒转化入刺糖多胞菌LW107129(NRRL30141)中,随后分离、发酵培养含雷怕霉素抗性基因的转化接合子。基因破坏实验的基础是当一个带有内部基因片段的质粒整合进来后,结果产生两个不完全的生物合成基因拷贝,从而消除酶的功能。分析发酵产物来确定哪种丁烯基-多杀菌素被积累了。busO基因的破坏导致丁烯基-多杀菌素PSA的累积,这暗示着busO基因为forosamine的合成和添加所必需(见实施例5)。利用forosamine生物合成基因不能合成的C-17位含有糖的化合物在busO突变株中也能累积。现在将要结合BLAST搜索、基因破坏实验和生物转化研究几方面结论,通过基因基础详细讨论一个基因。由于PKS上游的14个基因同刺糖多胞菌的spnF基因有很高的相似性,并且BLAST搜索结果显示这些基因同已知的编码丁烯基-多杀菌素生物合成所需的酶基因有着惊人的相似性。因此,可认为它们参与了丁烯基-多杀菌素的生物合成。
busF,busJ,busL,busM
基因busF,busJ,busL和busM同spnF,spnJ,spnL和spnM有很高的相似性。据报道,这些A83543多杀菌素基因参与了从推测出的PKS基因的单环内酯产物生成糖苷配基的过程。busF的基因产物同spnF的相比具有91%氨基酸同一性。同样地,busL的基因产物同spnL的相比具有94%氨基酸同一性。据报道,spnF和spnL基因产物均为甲基化转移酶,并且4个蛋白同已知参与C-C键形成的来自链霉菌的酶有很高的相似性。busJ蛋白同报道为氧化还原酶的spnJ蛋白有83%的氨基酸同源性。busJ和spnJ同dnrW都有高度相似性,已知后者在柔红霉素的生物合成过程中参与C-C键形成。busM基因产物同spnM基因产物96%同一性,而busM和spnM基因产物与来自于白色假丝酵母的一类新的分泌型脂酶高度相似。busF和busL基因产物的功能是作为甲基化转移酶,而busJ基因产物作为氧化酶,busM基因产物作为脂酶则同报道的spnF,spnJ,spnL和spnM基因产物在C-C桥形成过程中所起的作用相一致。
busG,busH,busI,busK
基因busG,busH,busI和busK同来自于刺糖多胞菌的基因spnG,spnH,spnI和spnK有很高的相似性。据报道,这些基因参与向A83543多杀菌素糖苷配基添加鼠李糖的反应以及接下来的甲基化反应。busG基因同spnG基因有90%相似,而同参与向聚酮化合物衍生的抗生素上添加糖基反应的几个基因也高度相似(表11)。busH,busI和busK基因产物分别同spnH(97%),spnI(92%)和spnK(88%)基因产物有很高的氨基酸相似性,spnH,spnI和spnK的基因产物被报道参与多杀菌素生物合成过程中鼠李糖的甲基化反应。BusH,busI和busK 3个基因同来自于链霉菌属弗氏链霉菌(Streptomyces fradiae)的基因tylE(busI和busK)和tylF(busH)有高度的氨基酸相似性,tylE(busI和busK)和tylF(busH)基因产物经实验证明为macrocin-O-甲基化转移酶(Bate和Cundliffe,1999)。
busN,busO,busP,busQ,busR和busS
基因busN,busO,busP,busQ和busS同来自于刺糖多胞菌的基因spnN,spnO,spnP和spnQ,spnR和spnS有很高的相似性(表12)。据报道,这些基因参与了forosamine糖的生物合成或添加。busP同其它的糖基化转移酶(表11)的相似性表明busP编码这种丁烯基-多杀菌素forosamyl转移酶。busO和urdS 2,3-脱水酶(表11;Hoffmeister等人,2000)之间的高度相似性说明busO参与了forosamine生物合成过程中的2’-脱氧步骤。busQ基因产物和urdQ3,4-脱水酶(弗氏链霉菌;Hoffmeister等人,2000)之间的相似性表明busQ参与forosamine生物合成过程中的3’-脱水步骤。busR与一组被认为功能是脱氧糖转氨酶的蛋白有着高达40%的同一性(Thorson等人,1993),这表明busR参与forosamine生物合成过程中的4’-胺化步骤。而busS同氨基甲基化酶之间的高度相似性则表明busS参与了forosamine的4’-氨基基团的甲基化过程。因此,busN,busO,busP,busQ和busS这些基因都参与丁烯基-多杀菌素的forosamine部分的产生。来自于刺糖多胞菌LW107129(NRRL30141)的19个基因在丁烯基-多杀菌素的生物合成过程中被赋予了功能5个PKS基因负责产生大环内酯,4个基因负责将这个大环内酯修饰成糖苷配基,4个基因负责添加和修饰鼠李糖,还有6个基因用于合成和添加forosamine。图S.1A和1B中概述了推测出的这个生物合成途径。
用途
克隆的刺糖多胞菌丁烯基-多杀菌素DNA有很多用途。这些克隆的基因可用以提高丁烯基-多杀菌素的产量并生产新的丁烯基-多杀菌素。产量的提高通过将一或更多的丁烯基-多杀菌素生物合成基因的复制拷贝整合进入具体的丁烯基-多杀菌素生产菌株的基因组中而得以实现。在一种极端情况下——在由于缺乏所需要的酶而其生物合成途径被中断的特定的突变菌株中,可以通过整合所需的基因拷贝恢复多杀菌素的生产。利用克隆DNA片段去破坏丁烯基-多杀菌素的生物合成步骤可以产生新的化合物。这种破坏可能会导致前体或“旁路(shunt)”产物(天然加工得到的前体衍生物)的累积。通过破坏基因的方法产生的被修饰多杀菌素可能本身是昆虫控制剂,也可能作为进一步化学修饰的底物并产生新的带有独特性质和活性谱的半合成多杀菌素。busQ基因的断裂会导致丁烯基-多杀菌素PSA的累积。丁烯基-多杀菌素PSA作为起始物质对于合成在C-17处含有新基团的多杀菌素类似物有用。通过将一或更多克隆的bus基因或它们的一部分转移到异源宿主内也可以产生新的丁烯基-多杀菌素。这些基因可以提供受体细胞中不存在的酶功能。这样的基因可能提供另一种糖基、修饰已经存在的糖基或糖苷配基碳原子,并允许另一种糖基连到糖苷配基上或改变此糖苷配基本身的基本结构。将克隆的bus基因转移到异源宿主内所产生的化合物可能本身作为昆虫控制剂,也可能作为进一步化学修饰的底物以产生新的具有独特性质和活性谱的半合成多杀菌素。来自于粘粒8H3和9D3的刺糖多胞菌LW107129(NRRL30141)DNA可以被转移到刺糖多胞菌-A83543的产生者中,并且此转化结合子可产生新的多杀菌素。诱变克隆的基因以及用突变基因去替换产丁烯基-多杀菌素的生物中未突变的相应部分也能产生新的丁烯基-多杀菌素。诱变可包括,例如1)缺失或失活KR、DH或ER结构域使得一或更多个相应功能被阻断,并且导致该菌株产生具有内酯核的多杀菌素,此内酯核含有双键、羟基或并不存在于多杀菌素核A上的酮基(见Donadio等人,1993);2)取代AT结构域使得不同的羧酸整合到内酯核上(见Ruan等人,1997);3)向已存在的PKS模块上添加KR,DH或ER结构域使得该菌株能产生具有内酯核的多杀菌素,而此内酯核上含有多杀菌素A核上不存在的饱和键、羟基或双键(MacDaniel和Katz,2002);4)增加或删减完整的PKS模块使得这个环内酯上碳原子的数目增加或减少。来自于丁烯基-多杀菌素基因簇区域的DNA可作为杂交探针去识别同源序列。因此,该克隆DNA可用于定位来自于刺糖多胞菌LW107129(NRRL30141)基因文库的另外的质粒,既包括这里所描述的区域,同时也含有过去未克隆的来自于刺糖多胞菌LW107129(NRRL30141)基因组邻近区域的DNA。另外,剌糖多胞菌LW107129(NRRL30141)基因同S.spinosa spn基因的比较结果有助于鉴定不同于非多杀菌素生产的生物合成基因(如红霉素、雷怕霉素、泰乐美等的生物合成基因)的保守序列区域。这些多杀菌素特异的基因探针和来自于这个被克隆区域的全部DNA都可用于鉴定其它生物体内非同一但相似的序列。正常情况下,杂交探针至少长约20个碱基,并被标记以便检测。按照诸如美国专利NO.5,362,634或2001年3月21日提交的临时美国专利申请60/277,601“大环内酯类杀虫剂”所提到的传统方案,通过培养本发明提供的修饰菌株可生产多杀菌素。上述实施例是非限制性的而不应该作为本发明的限制。
实施例2利用LC-MS分析发酵液中丁烯基-多杀菌素代谢产物
下述方法利用以电喷雾质谱(ESI)监测发酵液中分子式(1)和其它成分产生的高效液相(HPLC)分离。通过分析电喷雾加成(adduct)离子,该系统可用来测定纯化的物质的分子量。表15给出了相关数据。加入与发酵液等体积的变性乙醇。振荡混合物1小时,离心,过滤(孔径0.22μm)以除去大量的细胞碎片。微量离心1ml等分样品,然后用下述LC-MS系统去分析澄清的提取物。HPLC系统柱固定相250×4.6mm柱,基质钝化的硅胶,5μmC8(Hypersil-C8-BDS)。流动相10mM乙酸铵-甲醇-乙腈线性梯度如下
表14
其中溶剂A10mM乙酸铵及溶剂B甲醇-乙腈(1∶1);流速1mL/min;样品经过紫外检测器后被质谱断裂,因此MS废物比例为约5∶95;检测ESI正谱在高弧电压和低弧电压下获得;LC特征保留时间和特征质谱离子峰在表15中给出。
表15
a是指在+ESI模式中,低电弧电压下得到的母离子的m/z;b是指在高电弧电压下,+ESI中观察到的主要丰富片段及加成离子的m/z。
实施例3通过发酵制备丁烯基-多杀菌素代谢物
通过在发酵培养基(配方如下)中培养所需的刺糖多胞菌,其选自菌株NRRL30141、NRRL30142或其衍生物,来生成分子式(1)中的代谢物。先将1.8mL冷冻的生长培养物融化,然后接种于25mL生长培养基中,于30℃,150rpm,在125ml锥形瓶中培养72~96小时。
表16
摇瓶发酵
取12mL第一阶段成熟菌种,接种于盛有50mL发酵培养基的500mL有挡板的锥形发酵瓶中。
表17 将发酵液在30℃,200rpm(50mm搅拌(stroke))条件下培养7~12天。然后将成熟的发酵液用合适的溶剂抽提,用色谱分离法回收代谢产物(见实施例1中的公开部分)。
实施例4用粘粒8H3对菌株NRRL30421中鼠李糖甲基化缺陷的互补
菌株NRRL30421是刺糖多胞菌NRRL30141的突变种,它不能使丁烯基-多杀菌素上的鼠李糖完全甲基化,只能积累化合物4及在3’位置缺少O-甲基化的其它丁烯基-多杀菌素(3’-ODM)。这一甲基化缺陷被认为是busH、busI或busK基因编码的O-甲基转移酶之一突变的结果,而所有上述基因都存在于粘粒8H3中(见图2)。通过接合转移将大肠杆菌ATCC 47055中的粘粒8H3(见图3)转入菌株NRRL30421中(Matsushima等,1994),然后将两株用粘粒8H3转化的单菌落用实施例2中的方法发酵,再用实施例1中的方法分析化合物1和化合物4的生产。
表18
*在鼠李糖3’位置防止甲基化的突变菌株。菌株NRRL30421主要生产化合物4,而含有粘粒8H3的NRRL30421菌株则主要生产化合物1(表18)。含有粘粒8H3的NRRL30421菌株中化合物1和4的产量与未突变的NRRL30141中的大致相同(表18)。这表明用粘粒8H3转化能够克服菌株NRRL30421鼠李糖甲基化缺陷,并可恢复提高的化合物1的产量。
实施例5丁烯基-多杀菌素前体和由busO基因破坏所产生的旁路产物(ShuntProduct)的累积
通过整合busO基因内部片段而使busO基因失去活性。用寡核苷酸链对(一个对应于SEQ ID NO2中的碱基11882~11861,另一个对应于SEQ ID NO2中的碱基10970~10993)去扩增912bp大小的片段(位于1457bp的busO基因中),该片段对应SEQ ID NO2中的碱基10970~11882。用含有该片段的质粒转化刺糖多胞菌LW107129(NRRL30141)会导致busO基因的部分复制,从而产生在质粒两侧的及抗生素抗性基因的截短的基因两个拷贝。在FailSafeTMPCR仪(Epicenter)中用SEQ ID NO33和34作为引物扩增912bp的busO基因内部片段,然后按厂商(Invitrogen)的说明把扩增的片段克隆入pCRII中,产生的质粒用EcoRI消化,随后busO基因内部片段被克隆到pOJ260的EcoRI位点内。产生的新质粒通过接合转移(Matsushima等,1994)的方式从大肠杆菌ATCC 47055转移到刺糖多胞菌NRRL30121的衍生菌株中。然后将6个独立的阿泊拉霉素抗性接合后体分别按实施例2中的方法发酵培养,并按实施例1中的方法分析化合物1和其他的多杀菌素衍生物的生产。亲代菌株NRRL30141产生高水平的化合物1和低水平的假糖苷配基(Pseudoaglycone)PSA;化合物13)以及少量的化合物9(表19)。在6个busO突变菌株中均未检测到化合物1,这意味着busO基因是丁烯基-多杀菌素完全生物合成所必需的基因。另外,PSA在所有6个busO突变菌株中的表达水平均增加(可由Forosamine供应不足预测得知),C-17位上连有非Forosamine糖的化合物9在busO突变菌株中的表达水平也增加。
表19
*表中报导的数量是同NRRL30141中化合物13相比得出的结论。
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序列表<110>Hahn,DonaldJackson,JimBullard,BrianGustafson,GaryWaldron,CliveMitchell,Jon<120>用于生产丁烯基-多杀菌素杀虫剂的生物合成基因<130>51609<140>
<141>
<150>us 60/280,175<151>2001-03-01<160>40<170>PatentIn Ver.2.0<210>1<211>75236<212>DNA<213>刺糖多胞菌 NRRL30141<400>1atgagcgaag ccgggaacct gatcgccgtc gtcggattct cctgccgcct accccaggca 60cctgacccgg cttctttctg gcggttgctg cgcaccggaa cggacgccat caccaccgtc 120ccggaagggc ggtggggcga cccgttgccc ggccgggatg cgcccaaggg cccggaatgg 180ggcggcttcc tggctgatgt cgactgcttc gatcccgagt tcttcgggat ctcgccgcga 240gaagcggccg ccatggaccc ccagcagagg ctggctctgg agctcgcctg ggaggctctc 300gaagacgccg gtatccccgc cggcgagctg cgcggcactg ccgcgggggt gttcatgggg 360gcgatctctg acgactacgc cgccctgctt cgcaagagcc cgccggaagt ggctgcgcag 420taccgtctca ccggcaccca tcgaagtctg atcgccaacc gcgtgtccta cgtgctcggc 480ctgcgcgggc caagcctgac ggtggattca ggtcagtcct cgtccctggt cggcgtgcat 540ctcgccagcg agagcctgcg acgtggcgag tgcgcgatcg ctctcgccgg cggcgtgaac 600ctcaacctgg ctgccgagag caacagagcc ctgatggact tcggcgcgct ctccccggac 660ggtcgctgct tcaccttcga tgcgcgggcg aacggttacg tccgcggcga aggcggcggc 720ctcgtcgtgc tgaagaaggc cgatcaggct cgcgccgatg gcgaccggat ctactgcctc 780atccgcggca gcgcggtcaa caacgacggg ggcggtgctg ggctcacggc tccggcggca 840gacgcccagg cggagttgct gcgacaggca taccggaacg cgggtgtcga cccggccgcc 900gtgcagtacg tcgagctcca cggcagcgcg accagagtcg gggaccccgt cgaagcagca 960
gccctcggat ctgtcctggg tgtggcaaga cggcccggcg acaagctgcg tgtggggtcg 1020gcgaagacca acgtcggcca tctggaagca gcggcgggcg tcaccgggtt gctgaagacc 1080gcactcagca tctggcaccg cgaactgccg ccgagtcttc acttcaccgc ccccaacccg 1140gaaatcccgc tggacgaact gaatctacgc gtccagcgtg atctgcggcc gtggccggag 1200agcgagggcc cgctgctggc cggcgtcagc gccttcggaa tgggaggcac gaactgccac 1260ctggtgctct ccgattcgtc ccaggtggag cgaaggcgta gtggacccgc tgaggcgacc 1320atgccttggg tcttgtcggc cagaacaccg gtcgcattgc gtgcgcaggc ggcgcgcttg 1380cacacgcacc tcaatactgc cggtcaaagt ccattggacg tcggctactc actggcgacc 1440actcgatccg cgctaccgca ccgagccgcg ctggtcgcgg acgacgtacc gaaactgctc 1500gccgggttga aggccctcgc tgacggcgac gacgcgccca cgctgtgcac gggcacgact 1560tccggcgagc gggcaacagt cttcgtcttt cccggacagg gcagccagtg gatcgggatg 1620ggtaggcagc tgctccaaac ctccgaggtt ttcgcggcgt ccatggcgga ctgcgcggat 1680gcgttggcgc cgcacctgga ttggtccctg ctggatgtgc tgcgtaacgc ggccggcgct 1740tcgcagcttg atcgcgacga tgtcgtccag cccgcactgt tcgccgtcat ggtctcgctg 1800gcagagctct ggcgttcgtg gggcgtgcgt ccggaggcgg tcgtcgggca ctcgcagggg 1860gagatcgcgg cggcctgcgt cgccggggcc ctctccgtcc gcgatgccgc aagggtagtg 1920gcggtgcgca gcaggcttct ggcggcgctg gcgggcagag gcgcgatggc gtcgttgcag 1980catcccgttg aagaggtgcg acaaatcctg ttgccatggc gcgatcggat cggcgtggcg 2040ggggtgaacg gaccgtcgtc gactctggtg tcgggggacc gggaggcgat ggcggaactg 2100ctggccgagt gcgcgcgccg agagctccgg atgcgccgga ttccagttga atacgcctcc 2160cattcgccgc acatcgagga tgtccgcgac gagctgctgg cgctgttggc gtcgatcgaa 2220cccaggacag ggaacatccc ggtctattcg acgacgaccg gggaactgct ggaccggccg 2280atggacgccg actactggta ccgcaacctt cgtcaaccgg tgctgttcga agcggcggtc 2340gaggccctgt tgaagcgggg gcacaacgca ttcatcgaga tcagcccgca cccggtgctg 2400actgcgagca tccaggaaac cgccgcgcga gcggggcggg aggtagtggc gctcgggaca 2460ctccgccgcg gcgaaggtgg cctgcggcag gcgctgacgt cgctggccaa agcacacgtc 2520cacggagtgg ccgcgaactg gcacgcggtc ttcgccggca ccggggcgca gcgggtcgac 2580ctgccgacgt acgcctttca acgacagcgc tactggctgg acacgaaacc ttccgacctc 2640gccatgcccg agggcgatgt gtcgacagcg ttgcgggaaa aactgcgctc ctcgccgggg 2700gcggacgtgg actcagcgac cctcacaatt atccgggcac aggcagccgt ggtactcggc 2760
cactccgatc cgaaagagat ggactcggat cggacattca aagacctggg cttcgattcc 2820tcgaccgtgg tcgagctgtg cgaccgcctc aacgccgcca ccggactgcg cctcgcgccg 2880agcgtggttt tcgactgtcc gacgccctac aagctcgccc gccaggtacg gacgttgttg 2940ttggacgagc cagtccccac gacgtcaccc cgaacggaga ccgaagcgga cgagcctatc 3000gccgtgatcg ggatgggctg tcggtttccg ggtggcgtgt cctcgcccga ggagttgtgg 3060cagctggtcg ctgctggacg ggacgtcgtg tcagagttcc cggctgaccg aggttgggac 3120ccggagcgtg cggggacttc gcacgtgcgc gccggcggat tcctgcatgg cgccacggat 3180ttcgatcccg ggttcttcgg gatttccccg cgcgaggcgt tggcgatgga tccgcagcag 3240cgcttgctgc tggaaatcgc ctgggaggcg atcgaacgag gcgggatcaa cccgcagacc 3300ctgcacggaa gtcaaaccgg cgtcttcgtc ggcgcaacct ccctggatta cgggccacgc 3360ctgcacgaag cgtccgacga ggcggccggc tacgtgctca ccggcagcac cacgagtgtg 3420gcgtcgggtc gggttgcgta ttcgtttggt cttgagggtc ctgcggtgac ggtggatacg 3480gcgtgttcat cgtcgttggt ggcgttgcat ctggcgtgcc agtcgttgcg ttcgggtgag 3540tgtgatttgg cgttggccgg tggtgtgacg gtgatggcca cgccggggat gttcgtggag 3600ttttcgcgtc agcggggctt ggcacccgac ggtcgctgca agtcgttcgc ggaggccgcg 3660gatggcaccg gctggtccga gggtgccggc ctggttctac tggagcggtt gtcggatgcc 3720cggcggaatg ggcatgacgt tttggcggtg gttcgtggca gcgcggttaa ccaggacggc 3780gcgtcgaacg gactgactgc tccgaatggc ccgtcgcagc ggcgggtgat cacccaagca 3840ctcgccaacg cgaagttgtc ggtgtccgat gtggacgcag tggaggcgca cgggacgggc 3900acccggcttg gtgatccgat cgaggcgcag gcgctgatcg ccacttacgg gcagggacgg 3960ggtccggaac ggccgttgtg gttggggtcg gtcaagtcca acatcggtca tacgcaagcg 4020gcggccggtg ttgccggtgt catcaagatg gtcatggcga tgcggtatgg ggagctgccc 4080gccacgttgc acgtggacga gccctcctcg caggtggact ggtctgctgg gatggttcag 4140gttctgaccg agcacgtgcc ttggcccgac aacagccgtc ctcgtcgggt gggggtgtcg 4200tcgttcggga tcagcggcac caatgcgcac gtcatcctcg aacagtctcc gacagcgtca 4260agtgagttcg tggagcacag cggacctgat tcggaatctg ctgtggatgt tccggtggtt 4320ccgtgggtgg tgtcgggcaa aacgccggaa gcgctcagtg ctcaggcgga caacttggtg 4380tcctatctgg atgatcgccc taatgtttcc gcgctgaatg tggcatattc gctggcttcc 4440gaacgagccg cactggatga gcgggcggtg gtgctggggg cggatcgtga agcgttgttg 4500tctggactga aagcactggc tgccggtcac gaggatcctg gtgtggcgtc gggatccctg 4560
gtttctggtg gggttgggtt tgtgttctcc ggtcagggtg gtcagtggtc ggggatgggc 4620cgggggcttt accgggcgtt tccggtgttc gctgctgcct ttgacgaagc ttgtgccgaa 4680ctggatgcac atctgggcca ggaagtgggg gttcgggatg tggcgttcgg ttccgatgcg 4740cagttgctgg agcggacgtt gtgggcgcag tcgggtttgt tcgcgctgca ggtaggtttg 4800ctgaggctgt tgggttcatg gggtgttcgg ccgggtgcgg tgctggggca ttcggtgggc 4860gagttggcag cggcgcacgc ggcgggtgtg ttgtcgttgc cggatgcagc tcggttggtg 4920gcgggtcgtg cccggttgat gcaggcgatg ccggatggcg gtggcatgct cgcggtggct 4980acaagtgaga cccaggtcga acctatgctg gatggagtgc gggaccggat cgggatcgcg 5040gcgatcaacg ctccggaatc ggtcgtgctc tccggtgacc gcgaactact cgccgaagtc 5100gctgatcagc tgaacgatca agggtgccgg acacgatggt tgcaggtgtc tcacgctttc 5160cattcgtatc ggatggaacc gatgctcgac gagttcgccc agatcgcagg cagcgtggat 5220ttccggcgtt gcgaactgcc tatcatctcg accctgacag gaaacctcga tgacgtcggc 5280gtgatggcta cgccggagta ttgggtgcgt caggtgcgtg agcccgtccg cttcgccgat 5340ggtgtccagt cgctcgtcga gcaagatgtg gctactgttg tcgagcttgg ccctgatgcg 5400attctgtcgg ctctgattcc tgattgtcat tcctggggtg atcagactgt gccgattccg 5460ttgctgcgca aggaccgcgc tgaacccgaa actgtggtcg ccgcggtggc gcgggcgcac 5520acgcgtggtg ttcaggtcga ttggtcggcg tttttcgctg gtaccggggc tgggcgggtc 5580gagttgccga cgtatgcctt ccagcggcag cggtattggc tggagtcatc ggtttccggt 5640gatgtgacag gtatcggtct ggctggggcg gagcatccgt tgctgggggc cgtggttgtg 5700ttggccgacg gtgatgggat ggtgttgacc ggtcggttgt cggtggggac gcatcggtgg 5760ctggccgagc atcgtgtgct gggggaggtc gtggttcccg gcacggctat cctggagatg 5820gtcttgcatg cgggggcgcg ggttggttgt ggccgggtgg aggagctcac cctggaagca 5880ccgctggtgg tgcccgaacg cgatgccatc gaaatccagc tgctggtgaa cgcgcccgac 5940gacaagggtc ggcggtccgt gtcgctgcat tcccgcccgg ccggtgggtc tgggggtggg 6000ggttggacgc ggcacgccac gggcgaactc gtcgtcgccg gcacgggtgg tggggcggtt 6060actggttggt cgactgaggg tgccgagccg gttgctctcg gtgagtttta tgtcgttcag 6120gcggggaacg ggttcgagta tgggccgttg ttccaggggc ttcgggcggc gtggcgtcgt 6180ggtggcgagg ttctcgcgga ggtcgccctg ccggcagcgg ctggtgcgat ggcggggttc 6240ttgatcaatc cggcgttgct ggatgccgcc ttgcaggcgt ccgcgctggg tgaccgtccg 6300gcggagggtg gtgcgtggct gccgttctct tttaccgggg tagaactttc cggtcagggt 6360
gggacgatca gcagggcacg ggtggagtct acgcgacccg atgcggtgtc ggtggctgtg 6420atggatgagg gtgggcggtt gctcgcctcg atcgattctc tccggttgcg gccggtgtcg 6480tcggtgcggt tggcgaatcg ggacgttgtc ggtgacgcgc tgttcgaggt gacttgggag 6540ccggtggcga cgcggtcgac ggtatcgggt cgctgggcgt tgcttggtga tgctgtcggc 6600ggcatggccg gtctcattgg gctcgcacca ggttccgtcg atcgttgtgc gggtctggct 6660gagctcgcgg ggaaccttga ttccggtgcg ctggttgctg atgtcgtggt ttattgcgcc 6720ggtgaacagg cggatcccga cgccggcgtg gcggcactcg cggagacccg ggagatgctg 6780gccctggtcc agtcgtggtt ggccgaggag cggttggccg ggtcacgtct ggtggtggtg 6840acgtgtggcg cggtgacgac ggctgcgggt gacggcgcat caaagctggc gcatgcgccg 6900ttgtgggggt tgttgcgttc agcgcagtcg gagaacccgg gccggtttgt gctggtcgat 6960gtggacggta ccgccgagtc gtggcgcgcg ttgccgagtg cggtggggtc gatgcaaccg 7020cagttggccg tgcgtaaggg tgtggtgaca gtgccgcgtg tggcgtcggt tccggggccg 7080gtcgaggtgc ccgcggtggt ggccggtccc gaccggacgg tgctgatttc cggtggcacg 7140ggtctgttgg gtggcgtggt ggcacgccac ctggtggccg agcgcggtgt tcgtcgagtg 7200gtgttgacgg gccgtcgtgg ctgggatgct cccggaatca ccgagttggt gggtgagctg 7260gagggtttcg gtgcggtggt cgatgtggtg gcgtgcgacg ttgcggatcg tgctggtctg 7320gaggggttgc tggcggcggt cccggcggag tttccgctgt gtggtgtggt gcatgccgcg 7380ggtgtgctgg ctgacggggt gatcgagtcg ttgacaccgg aggacgtggg ggcggtgttc 7440ggtccgaagg cggcgggggc gtggaacctg cacgagctga ctcgggatat ggacttgtcg 7500tttttcgcgt tgttctcctc gctgtccggg gtgaccggcg ccgcgggtca gggtaattat 7560gcggcggcga acacgttcct ggacgcattg gcgcattacc ggcgggcgca gggattgcct 7620gcggtgtcgt tggcgtgggg cttgtgggag cagtcgagcg ggatgaccgg gcggctcagt 7680gatgtcgacc ggagcaggat cgcccgctcc agtccaccgt tgtccaccaa ggatggtttg 7740cggctgttcg atgccgggct ggcgttggat cgggcagcgg tggttccggc gaggttggac 7800agggccttcc tggccgagca ggcccggtcg ggaacgctac ccgcgatgct gacggcactg 7860gtacctacca tcacctctat caggcgcagt agtggcaccg acctcgcgga cgaggacgcc 7920ttgcttgggg tggtgcggga gcacgccgcg agggtgctgg ggtattcggg tgcggccgag 7980gtcggggtcg agcgtgcttt ccgggatctg ggctttgatt cgttgtctgg tgtggagttg 8040cgtaatcggc tggccggggt gctgggagcc cggctgccgg caaccgccgt attcgactac 8100ccgacgccgc gggcgttggc ccggttcctg caccaggaac tggcaggcga ggtcgggacg 8160
acgccggcgc cggtgacgac cacgaccgcg agcgtcgaag acgatctcgt cgcgatagtc 8220gggatggggt gtcgttatcc gggtggggtg tcctcaccgg aggagctttg gcgtttggtg 8280gccgggggcg tggatgcggt cgcggacttc ccggacgatc gcggctggga tctggccgga 8340ttgttcgatc cagatcccga tcgtttcggg acttcgtatg tgcgtgaggg cgggttcctg 8400cgggacgcgg cggagttcga tgccgcgttt ttcgggattt ctccgcgtga ggcactggcg 8460atggacccgc agcaacggtt gctgctggag ctgtcctggg aggccgttga acgcgctggg 8520atcgatccgg ggtcgctgcg cgggagccgg acgggtgtgt tcgcggggct gatgtatcac 8580gactacgccg gacggttcgc ggccggagtg ccggagggct tcgaaggcta tctcggtaat 8640ggcagcgcgg gcagtgtggc ctcgggccgg gtcgcgtatt cgttcggttt cgagggtcct 8700gcggtgacgg tggacacggc gtgttcgtca tcgctggtgg cgttgcacct ggcaggtcaa 8760tcactgcgtt ccggtgagtg tgatctcgcc cttgccggtg gcgtgacggt gatggccacc 8820ccggcgacgt ttgtggagtt ctcccgtcag cggggtctgg caccggatgg gcgctgcaag 8880tcgttcgcgg aggccgcgga cgggaccggc tggggcgagg gtgctggcct agtgctgttg 8940gagaggttgt cggatgcccg tcgtaatggg catcgggtgt tggcggtggt tcgtgggtcg 9000gcggtgaatc aggacggcgc gtcaaacgga ctgaccgcgc cgaatggtcc ctcgcagcaa 9060agggtgatca cccaagcact cacgagtgcg gggttgtccg tgtccgatgt ggatgctgtg 9120gaggcgcacg ggaccgggac caggcttggt gatccgatcg aggcacaggc attgatcgcc 9180acctatggcc gtgatcgtga tcctgaccgg ccgttgtggt tggggtcgat gaagtccaac 9240atcggtcaca cacaggcagc ggcgggtgtt gccggtgtga tcaagatggt gatggcgatg 9300cgccacgggg agctgccgcg cacattgcac gtcggcgagc ccacgtcgga ggtggattgg 9360tcggcaggtt cggtccagct cctcacggag aacacgccct ggcccgacag cggccatcct 9420cgtcgggcgg gagtgtcgtc gttcgggatc agcggcacca acgcacacgt catcctcgaa 9480cagtctccga cagcgtcaag tgagttcgtg gagcacagcg gacctgattc ggaatctgct 9540gtgaatgtcc ctgtggttcc gtgggtggtg tcgggcaaaa cacccgaagc gctcagtgct 9600caggcggaca ccttggtgtc ctatctggac gatcgatctg atgtctcctc gcgggatgtt 9660gggtattcgc tggcgatgac gcgttcggcg ctggatgagc gggcggtggt gctggggtcg 9720gaccgtgaaa cgttgttgtc cgggttgaaa gcactggctg ccggtcatga ggccactggg 9780gtggttacgg gatctgtggg ttctggcggc cggcccggtt ttgtgttcgc cggtcagggt 9840ggtcagtggt tggggatggg ccgggggctt taccgggcgt ttccggtgtt cgctgatgcc 9900tttgacgaag cttgtgccgg actggatgcg catctggggc agaaagtggg ggttcgggat 9960
gtggtgttcg gttccgacgc gcagttgctc gatcggacgt tgtgggcgca gtcgggtttg10020ttcgcgttgc aggttggttt gctgaagttg ttgggttcgt ggggtgttcg gcctgttgta10080gtgctgggcc attcggtcgg ggagctagca gcggcgttcg ccgccggtgt gctgtcgatg10140gcggaggcgg ctcggttggt ggccggtcgt gcccggttga tgcaggcgtt gccgtctggc10200ggtgccatgc tcgcggtggc gacaagtgag acccaggtcg aacctttgct ggatggagtg10260cgagaccgga tcgatatcgc ggcgatcaac gctccggaat cgatcgtgct ctccggtgac10320cgcgaactac tcaccgaagc cgctgatcag ctgcacgatc aagggtgccg gacacggtgg10380ttgcaggtgt cacacgcctt ccattcgccc cagatggatc cgatgctgga cgagttcgcc10440gacatcgcac gaaccgtgga tttccggggt tccgaactgc cggtcgtgtc gacgctgact10500ggtgcgctcg atgacagcgg cctgatggct acaccagagt attgggtgcg tcaggtgcga10560gagcccgtcc gcttcgccga cggggttcgg gcgctcgtcg agcacgatgt ggccactgtt10620gtcgagctcg gcccggacgg ggcgttgtca gcgctgatcc aggaatgtgc agccgaattc10680gatcagtcca gaagggtggc cgcggttccg gcgatgcgcc ggagccagga cgaggcgcag10740aaggtgatga cggccctggc gcaggtccat gtgcgtggtg gtgcggtgga ctggcggtca10800gttttcgctg gtacggggtc gaagcaggtc gagctgccga cgtatgcctt ccaacgacag10860cggtactggc tgaatgcggt gcatgaatct tctgccggcg acatgggtcg gcgtattgaa10920acggaattct ggagcgctgt cgagcacgaa gatgtgacat cgcttgcaaa catattgggt10980attgtggacg acggcgctgc cgtggattcc ttgcgaaacg cccttccggt gttggccggc11040tggcagagaa cccgtaatga cgagtcgatt atggatcggc agtgttaccg aatcggctgg11100aggcaggtag ccggactccc gccaagggga accgtcttcg gcacttggct ggtcttcgca11160ccccatggct ggtccggcga accgcaggtg gcgaactgcg ttgcggcatt gcgggcaagc11220ggtgcctcgg tggtgttggt ggaagctgat cccgacccgg tcgtcttcgg cgaccgggta11280cggaccctgt gttcggactc tccggatctt gttggcgttt tgtcaatgct gtgcttggaa11340gaatcggcga ttccgggatt ttctgcggtg tcacggggtt ttgcgttgac cgtggagttg11400gtgcgggctt tggcggccgc tggtgcggat gcccggttgt ggttgctgac gtgtggtggc11460gtgtcggtgg gggatgtacc ggttcgtcca gagcaggcat tggtgtgggg gttggggcgt11520gttgcggggt tggagcatcc ggactggtgg ggcggcttga tcgatattcc ggtcttgttc11580gacgaagatg ctcaagagcg cttgtcgatt gtgctggcag gtctcggtga ggaagaggtc11640gcgatccgtt ctgacggcgt gttcgcacgt cggttggtac gccatggtgt ctcggctggt11700gtgaagaagg cgtggcgccc ccggggatct gtactggtga cgggcggcac gggtggtttg11760
ggggcgcacg ctgctcgctg gttggccgac gccggagccg aacatgtggt gatggtgagt11820cgacgcggag agcaggcacc gagtgcggag aaattgcgga cggaactgga ggatctgggt11880actcgggtgt cgatcctgtc atgcgatgtg accgatcgcg aagcactggc cgaagtgttg11940aaagcccttc cggctgaata tccattgact gcggtagtgc atacggcagg cgtgatcgag12000actggtgatg cggcgtcaat gagcttggct gatttcgatg acgtgttgtc cgcaaaggtg12060gctggtgccg cgaatctgga tgccttgctg gccgatgtgg aattggacgc gttcgtcttg12120ttctcatcgg tgtcgggagt ttggggcgct gggggacagg gggcttacgc ggcggcgaat12180gcctatctgg atgcgctggc ggaagagcgt cggtcgcgag ggttggtcgc gaccgcggtg12240gcgtgggggc cgtgggccgg cgaggggatg gccgccggcg aaacaggaga ccagctgcgt12300cgatacggcc tttccccaat gggtccgcag tacgccatcg ccggaattcg gcgggcagtg12360gaacaggacg aaatttccct ggtagtggcc gacgtcgatt gggcacgttt cagcgcggga12420ttcctggcgg ctaggccgcg gccactgctg aacgaactga ccgaggtcaa ggaactcctc12480gtcaatgctc agtccgaggt gggagtcgtt gccgaggcgt cggtggcatg gcggcagcga12540ttggccgcag caccgaggcc ggcacaggaa cagctgatcc tggagctggt acgcggcgaa12600acggctctgg tactgggaca tcccggagca gaggccgttg caccggaacg agctttcaag12660gacagcggat tcgactcgca ggccgcggtc gaactccgcg ttcggctcaa tcgagccacc12720ggcctccagt tgccatcgac aattatcttc agccatccca cgcctgcaga actggctgcg12780gagctgcggg cgaggctcct ccccgagtcc gcaggagtag acatttccga ggaggacgag12840gcgcgaatca gagcggcact gacgtcgatc ccgttcgcgg ccttgcgcga ggcagacttg12900gtgaatcgcc tgctcgccct tgccggacac ccagtcgact ccggcagctc cccggacgat12960gcggtcgcga cctcgatcga tgcgatggat gtagccgacc tcgtcgaagc agcgctgggc13020gaacgcgagt cctgagaccg cagacctggg agatcacggt gaccaccagt tacgaagaag13080ttgtcgaggc actgcgagca tcgctcaagg agaacgaacg cctccggcgc ggccgggatc13140gattcgccgc ggagaagggc gatcccatcg cgatcgtggc gatgagttgc cgttaccccg13200gtcaggtctc ctcgccggag gacttgtggc aactggccgc cggcggtgtg gacgcgatct13260ccgaagtccc gggggatcgc ggttgggacc tagccggcgt gttcgatccg gactccgatc13320gtcctggcac atcgtatgcc tgtgcgggcg gtttccttca gggcgtgtcg gagttcgatg13380cgggcttctt cgggatttct ccgcgtgagg cgttggcgat ggacccgcag cagcggttgc13440tgctggaagt cgcgtgggag gtcttcgaga gggctgggct ggagcagcgg tcgacacgtg13500gttcccgcgt tggcgtgttc gtcggtacca atggccagga ctacgcgtcg tggttgcgga13560
cgccgccgtc tgaggtggca ggtcatgtgc tgacgggcgg cgcggcagcg attctttcgg13620gtcgggttgc gtattcgttc gggttcgagg gtcctgccgt gacggtggat acggcgtgtt13680cgtcgtcgtt ggtggcgttg cacctggcgg gtcaagcact gcgcgctggt gagtgcgacc13740tcgcccttgc cggtggcgta acggtgatgt cgacgccgaa ggcgttcctg gagttctccc13800gccaacgtgg tctcgcggct gacgggcggt gcaagtcgtt cgcggcggcg gcggatggta13860ctgggtgggg cgagggtgcc ggactgttgt tgctggagcg gctgtccgac gctcgtcgaa13920acggacaccg ggtgttggca gtggtgcgag gtagcgctgt gaaccaggac ggtgcctcca13980acgggctgac cgcaccgaac ggttcttccc aggcgcgggt gatcacccag gcgttggcaa14040gtgcggggtt gtcggtgtct gatgtggacg cagtggaggc gcatggcacg ggcacgcggc14100ttggtgatcc gattgaggcg caggctctga tcgccaccta tggccgtgat cgtgatcctg14160ctcggccgtt atggttgggt tcggtcaagt cgaacatcgg tcatacgcag gcggcggcgg14220gtgtggccgg cgtgatcaaa atggtgatgg cgatgcggca cgggcagctg ccgcgcacgt14280tgcacgtgga cgcgccgtcg ccggaggtgg attggtcggc agggacggtc caactcctta14340cggagaacat gctttggccc gagagcggtc gtgttcgccg ggcgggggtg tcgtcgttcg14400ggatcagcgg caccaacgcg cacgtcatcc ttgaacagcc cacgggcgag acgcgtcagt14460cagcggggcc ggattcgggc tctgtcgtgg atgttccggt ggtgccgtgg atggtatcgg14520gcaaaacacc ggatgcgctc ggcgcccagg cggacacatt gatgtcctat ctggatgatc14580gtgttgacgt cccttcgctg gatattgcgt attcgctggc gatgacgcgt tcggcgctgg14640atgagcgggc ggtggtcctg ggtccggacc gcgaaacgtt gttgtccggg ttgaaagcgc14700tgtctgccgg gcatgaggct tctggggtgg ttacgggatc tgtggggact gggggacgca14760tcgggtttgt gttttccggt cagggtggtc agtggctggg gatgggccgg gggctctata14820gggcttttcc ggtgttcgct gctgcctttg acgaagcttg tgccgagctg gaggcacatc14880tgggccagga ggttggggtt cgggatgtcg tgttcggttc ggatgcgcag ttgctgaatc14940ggacgttgtg ggcgcagtcg ggtttgttcg cgttgcaggt cggtttgctg aagttgctgg15000attcgtgggg tgttcggccg agtgcggtgc tgggccattc ggtgggtgag ttggcggcgg15060cgttcgcggc gggtgtgttg tcgttgtcgg atgcggctcg gttggtggcg ggtcgtgccc15120ggttgatgca ggcgttgccg tcaggcggtg ggatgttggc ggtggctgct ggcgaggagc15180aactgcggcc gttgttggcc gatcacggtg atcgtgtggg gctcgctgcg gtcaacgttg15240cggagtcggt ggtgctctcc ggtgatcggg atgtgctcga tgacattgcc gggcggctgg15300acgggcaagg ggttcggaca cggtggttgc gggtttcgca tgcgtttcat tcgtatcgga15360
tggacccgat gctggacgag ttcgccgaaa tcgcacgagc cgtggactac cggcgttgcg15420aactgccgat cgtgtcgacc ctgacgggaa aactcgatga cgctggcagg atgagcggtc15480ccgactactg ggtgcgtcag gtgcgcgagc ccgtccgctt cgccgacggt gcccaggcac15540tcgtcgagca cgacgtggcc accatagtcg agatcggtcc ggacggggcg ttgtcggcgc15600tgatccagga atgtgtggcc gcatccgatc agtccagaag ggtggccgcg gtcccggcga15660tgcgcaggaa ccgggacgaa gcacagaact tgacaacagc cctggcgcag gtccatgtgc15720gtggtggtgc ggtggactgg cggtcgtttt tcgccggtac gggggcgaag caagtcgagc15780tgcccaccta tgccttccag cggcagcggt actggctgga gccatcggat tccggtgatg15840tgacaggtgc cggtctggcc ggggcggagc atccactgtt gggtgctgtg gtgccggtcg15900cgggtggtga tgaggtgttg ctgaccggca ggatttcggt ggggacccat ccgtggctgg15960ccgaacaccg ggtgctgggc gaagtgatcg tcccgggcac cgcgttgctg gagatcgcct16020tgcatgcggg ggaacgtctt ggttgtgaac gggtggaaga actcaccctg gaagcaccgc16080tggtccttcc ggagcgcggg gcgatgcagg ttcagctgcg agtgggtgcg cccgagaatt16140ccggacgcag gccgatggtg ctctactcgc gccccgaagg ggcggcggac catgactgga16200cacggcacgc cacgggccgg ttggcgccag gcggcggaga ggcggccgga gacctggccg16260actggccggc tcctggtgcg ctgccggtcg acctcgacga gttctatcgg gacctcgctg16320agcatggcct ggagtacggc ccgatcttcc aagggctcaa ggcggcctgg cggcaagggg16380acgaggtgta cgccgaagcc gcgctgccag gaacagaaga ctccggtttc ggggtgcatc16440cggcattgct ggacgcggct ctgcacgcaa cggctgtccg ggacatggat ggcgcatggt16500tgccattcca gtgggaaggt gtgtgcctgc acgccagggc cgcgtcggct ttgcgggtcc16560gcgtggtccc ggctggtgac gatgccaaat ccctgctggt gtgcgatggc accggtcgac16620cggtgatctc ggtggaccgg ctcgtgtttc ggtcggctgc ggccgggcgg accggtgcgc16680gccgacaggc ccatcgagct cggttgtacc ggttgggctg gccaacggtt caactgccga16740catccgctca gcccccgtcc tgcgtgcttc tcggcacctc ggaagtgtcc tctgacatgc16800aggtgtatcc ggacctccgg tcgttgacgg ccgcgttgga tgccggtgcc gaaccacccg16860gcgtcgtcat cgcacccacg ccccccggcg gtggacaaac agcggatgtc cgggagtcga16920ctcggcatgc actcgacctg gtacaaggct ggcttgccga tcagcgactc aacgattccc16980gattgttcct ggtgacacgg ggagcagtgg ccgtggagcc cggcgaaccc gtgaccgatc17040tggcgcaggc cgcgctctgg ggactgttgc gttcgacgca gaccgaacac cctgatcgct17100tcgtcctcgt cgatgtggct gagcccgcgc aactcctccc cgccctgccg ggggtgctgg17160
cctgcggcga gcctcagctc gcactgcgac gtggcggcgc acacgcgccc agactggctg17220gactgggcgg cgatgacgtc ctgcccgtgc cggacagcat ggggtggcga ttggaggcca17280cgagcccagg aactctggat ggcttggcat tgctggacga accggcggcc acggcatcgc17340tgggtgacgg gcaggtcagg attgcgatgc gcgctgccgg ggtgaacttc cgggatgcgc17400tcatcgcgct cggcatgtat cccggtgcgg cttcgctggg cggtgagggg gccggggtcg17460tggtggagac cggccccggc gtcaccggcc tggcacccgg cgaccgggtg atggggatga17520tcccgaaggc gttcgggccg ctcgcagtcg ccgaccatcg catggtgacg aggattcccg17580ctggttggag cttcgcgcag gccgcatcgg tgccgatcgt ctttctcacc gcctactacg17640cgctggttga tctcgccggg ttgagaccag gggagtcgct gctggttcat tcggccgccg17700gtggggtggg catggccgcg atccaactcg ccaggcacct cggtgcagag gtgtacgcca17760ccgcaagcga ggacaagtgg caagccgtgg agctgacacg agaacgcctc gcttcgtcgc17820ggacgtgcga tttcgagaag cagttcctcg gggcgaccgg cggacgcggc gtcgacgtcg17880tgctcaactc cctcgccggg gacttcgccg atgcgtccct gcgaatgctg ccgcgcggtg17940gccgtttcct ggagttgggg aagacggatg ttcgtgaccc cgtcgaggtc gccgatgcgc18000atccgggcgt gtcctaccag gcgttcgaca ccgtagaggc cggcccgcag cgaatcggcg18060agatgcttga cgagctggtg gagctgttcg agggaggcgt gctggagccc ctgcctgtca18120cggcttggga cgttcggcag gcgcccgagg cgctacgaca cctgagccaa gcgcggcatg18180tgggcaagct ggtgctcacc atgcctccgg cgtgggacac cgccggcacg gttctggtta18240ccggcggaac gggagcactt ggagcagagg tcgcccggca cctcgtgatc gagcacgggg18300tgcgcaacct ggtgctcgtc agcagacgcg gtcccgcagc cagtggcgct gctgagctcg18360tggcgcaact gacggcctac ggtgccgagg tttccctgca ggcgtgtgat gtcgccgatc18420gtgagacctt ggcgaaggtg cttgccggca tcccggacga gcatacgttg accgccgtgg18480tgcacgcggc tggtgttctc gacgacggag tggccgaatc gctcacagcg caacggctgg18540accacgttct gcgcccgaag gtcgatggcg cgcgcaatct gcacgagctg atcgcacccg18600acgtggccct cgtgctgttc tcgtcggtgt cgggcgtgct cggcagcggt gggcagggta18660attacgcggc ggccaactcc ttcctcgacg cattggcgca gcaaaggcag tcgcgcggcc18720tacctacgag atcgttggcc tggggtccct gggcggaaca tggcatggca agcaccttgc18780gcgaagccga gcaggataga ttggcgctat ctgggctgct gccgatctcg accgaggagg18840ggttgtccca gttcgacgcc gcgtgcggcg gcgcgcatac cgtggtggct ccggttcgaa18900tcggccgctc gtccgacggg aacccgatca agtttcccgt cctgcgaggc ttggtcgagc18960
cgcatcgcgt caacaaggcg accgcggatg atgccgagag catccggaaa cggttgggac19020gcttgccgga tgcagaacaa caccggattc tgctggacct cgtccgcacg cacgtggcgg19080cagtgctcgg attcgccggt ccccaggaga tcaccgcgga cggcacgttc aaggcgctgg19140gcttcgactc gttgaccgtg gtcgagttgc gcaaccggat caacggggca accgggctgc19200gactgcccgc caccctggtg ttcaactacc cgacgccgga tgcgctcgcc gcacacctcg19260tcaccgcgct ttccgcagac cgccttgccg ggacgttcga ggaactcgac aggtgggcgg19320cgaacctgcc cgcgctggcc agggatgagg ccacgcgggc gcagatcacc acccggctgc19380aggcgatctt gcagagcctg gcggacgtgt ctggcggaac cggcggcggc tccgtgccgg19440accggctcag atcggccacg gacgaagagc ttttccaact cctcgacaac gatctcgaac19500ttccctgatg cctcagccgg tgccttcgca gcttcctgga gggaaacgcc ccatgtcgaa19560cgaagagaag ctccgggagt acttgcggcg tgcgctcgtg gatctgcacc aggcgcgcga19620gcggcttgac gaggcggagt cgggggagca ggaacccatc gcgatcgtgg cgatgggctg19680tcggtacccg ggtggggtgc acgacccgga aggtctgtgg aaactggtcg cctccggtgg19740cgacgccatc ggtgaatttc ccgctgaccg tggttggcac ctcgacgagc tctacgatcc19800cgacccggat cagcccggaa cctgctacac ccggcacggc ggcttcctcc acgaggccgg19860cgagttcgac gcggggttct tcgacatcag cccccgtgag gcgctcgcca tggacccgca19920gcagcggctg ctgttggaaa tctcctggga gaccgtcgaa tccgctggga tggacccgag19980gtccttgcgg gggagccgca ccggggtgtt cgcgggattg atgtacgagg gctatgacac20040cggcgcccac ccggaaggtg tcgaaggcta tctcggaacc ggcaatgcgg ggagcgtcgc20100ctctggtcgg gttgcgtatt cgttcgggtt cgagggccca gcggtgacgg tggacacggc20160gtgctcgtcg tcgttggtgg ccctgcattt ggcgtgtcag tcgttgcggc agggcgagtg20220tgatttggcg ctggccggtg gagtgacggt gatggccacg ccggcgacgt tcgtggagtt20280ctcccgtcag cgtggtctcg caccggatgg gcggtgcaag tcgttcgcgg ctgctgcgga20340tggaaccggt tggggtgagg gtgccggctt ggtgttgctg gagcggctgt cggacgccag20400gcgcaacggg catcgggtac tggcggttgt tcgtggtagc gcggtgaatc aggacggtgc20460gtcgaacgga ttgacggccc ccaacgggct ggcccaggag cgggtcattc agcaggcgct20520cacgagtgcg gggctgtcgg tgtccgatgt ggacgttgtg gaggcgcatg ggacgggtac20580gcggcttggt gatccgatcg aggcgcaggc tctgatcgcc acctatggac aggatcggga20640ccgggatcgg ccgctgtggt tggggtcggt caagtccaac atcggtcata cgcaggcggc20700cgcgggcgtt gctggtgtga tcaagatggt catggcgatg cggcgcgggg agctgccgcg20760
cacgttgcac gtggacgagc cgaattcgca cgtggactgg tcggctggtg cggtccggct20820cctcaccgag aacatccggt ggccagggac gggtacgcgc cgagttggcg tgtcgtcgtt20880cggggtaagc ggtaccaacg cacacgtcat cctcgaacac gacccgctcg ccttgaccga20940gaacgagaac gcagcggtgt ccccagcacc tgggatcgtg ccttgggcgt tgtccgggcg21000gtcgtcgacg gcgctgcgag cccaggccga acggctgagc gagctgtgcg agcagaccga21060tcccgacccc gtcgacgtcg gtttctcact ggccaccacg cgcacggcct gggagcaccg21120agcggtggtg cttggtggtg atagcgctac attgcgttcc ggacttggcg ttgtcgctag21180cggcgaaccg gcagtcgatg tcgttcaggg gagcgtcctg ggcggcgagg tcgtcttcgt21240ctttcccggt cagggttggc aatgggccgg tatggcagtc gacttgctgg acgcttcgcc21300gacgttcgcg cggcacatgg acgagtgcgc caccgcgctg cggaagtacg tggactggtc21360gttggtcgac gtgctgcgcg gagcggagaa cgccccaccg ctcgaccggg tggacgtcct21420gcaaccggtg tccttcgcgg tgatggtgtc gctcgccgag gtgtggcgtt cctacggggt21480gcggccggcg gccgtcgtcg gccacagtca aggcgagatc gccgcggcct gcgcagccgg21540ggtgctgcca ctggaggatg cggccaggct tgtcgccttg cgcagcagag cgttgaaggc21600actatcgggg cgaggtggca tggcgtcgct ggcttgctct gcggatgagg ccgcggcgtt21660gttcgcggga ttgggcggtc gtctggaaat tgcggcgatc aacggcccgc gatcggtcgt21720ggtgtccggc gatctggaag cggtggaaga actgctggca gagtgcgctg aaagggacat21780gcgtgcacgc cgtatccccg tcgactacgc ctcgcattcg gcacacgtgg aggtggttcg21840gagcccggtg ctggcggctg cggccggcgt gcggcaccgg gacggccagg tgccgtggtg21900gtcgacggtg atcggcgact ggttggatcc ggccgggctg gacggcgagt actggtaccg21960gaacctccgg cagccggtcc gattcgaaca cgccgtgcag ggcctggttg agcggggatt22020cggcctgttc atcgaaatga gtgcgcatcc ggtgctgacc atggcggtcg aggaaaccag22080tgccgagtcg gagtccgccg tggccgcggt aggtaccttg cgacgtgact cgggcggccg22140ccggaggttg ttacagtcgc tggccgaggc gtacgtgcgc ggcgccaccg tggactgggc22200cgtggcgttc gggggcgtgg gtcgacggct ggacctgccg acctacccgt tccagcgccg22260gcggtactgg ctggacaggg gagctgcctc cgaggaggct cgtgcgtttt cggacccggc22320ggcggactgg ttctggcaag ccgtggagcg ccaagacctg aaaggcgtgg ccgacgccct22380cgatctcgac gccgacgcac cgctgagcgc aacacttccg gccctgtccg tctggcaccg22440tcaggaacga gaaaaggtct tggtggacgg ttggcggtac cgagtcgact gggtaccggt22500ggccccgcag ccgatccgga gaacacggga aacctggctc ctggtcgttc ccgcgggcgg22560
cattgaagaa gcgctggtcg aacggttgac ggatgcgttg aacacgcgag ggatcagcac22620cctgcgcctc gacgtgccac cgacggcgac aagtggggaa ctcgcgaccg gcctccgcgc22680cgcagttggc ggtgacccgg tgaagggaat cctgtcgctc actgcgttgg acgagcgaac22740acaccccgaa cgcaaggccg tccccagcgg gattgccttg ctgttgaacc tggtcaaggc22800gctcggtgaa ggcgacctca gagttcctct gtggacgatc acgcgtggtg cggtcaaggc22860agaccccgca gatcggctgc tgcgcccgat gcaggctcaa gcatggggtc tggggcgagt22920agccgcactc gaacaccccg agcgctgggg tgggctgatc gacctcccgg aatcgctgga22980cggcgacgtc ctcacaaggt tgggcgaagc gctcatcaac ggcttggcgg aggaccaact23040ggcgattcgc cagtcgggcg tgctggcccg gcgcctggta ccggccccgg cgaatcagcc23100cgctggacgt aagtggcgac cccgaggtag cgcgctgatc acgggcgggc tcggcgcggt23160gggcgcgcag gtggcgaggt ggttggccga aagcggagcc gagcgaatcg tgctcaccag23220tcgacggggc aaagaagcgc cgggcgccgc agagctggaa gccgaactcc gggcccttgg23280agcgcaagtg tccatcgtgg cttgtgacgt gaccgatcgt gccgagatgt ccgcactgct23340ggccgagttc ggcgtcaccg cggtgttcca cgcggccgga gtcggccggc tgctgccgct23400ggcggaaacc gaacagaacg acctggccga aatatgcacg gccaaggttc acggcgctca23460ggtgttggac gagctgtgcg acagcaccga tctcgatgcc ttcgtcctgt tctcctcggg23520tgccggggtc tggggcggtg gcggtcaggg cgcctatggc gcggcgaacg cattcttgga23580cacactcgcc gaacaacgcc gagcacgcgg tctgccggca accgcgatct cctggggcag23640ctggggcggc ggcatggccg acggcgcagc gggcgaactc ctgcggcgac ggggaatacg23700tccgatgccg gcggcgtcgg ccatcctggc tctgcaggaa gtactcgacc aggatgagac23760gtgcgtgtcg atcgctgatg tggactggga ccgattcgtg cccacgttcg ccgcgacccg23820cgccacccgg ttgctggacg aactgcccgc ggtgagaaag gcgatgtccg cgaacgggcc23880ggcagaacca ggcggctcgc cgttcgcccg caatctcgcg gagctgccgg aagcccaacg23940acgccacgaa ctggtagatc tggtcagcgc ccaggtggca gccgtgctcg ggcacggcag24000tcgcgaggaa gtccagcctg aacgggcgtt ccgcgcgctc gggttcgact ccctcatggc24060ggtggacctg cgcaatcgtt tgaccaccgc caccgggttg cgcctgccga ccacaactgt24120cttcgactac ccgaatccgg ccgcattggc cgctcacctg ctcgaggagc tggtgggcga24180tgtcgcgtcg gccgcggtga ccactgccat cgcgccgtcg actgacgaac cggtcgcgat24240cgtcgcgatg agctgccggt tccctggcgg cgcgcactcg ccggaagacc tgtggcggct24300ggtcgcctcc ggcgcggagg tgatcggcga gttcccctcc gaccggggtt gggatgcgga24360
aagcctctac gatccggacg cttccaaacc tggaaccacg tatgcgcgga tggcgggatt24420cctttacgac gccggtgagt tcgatgccgg cttgttcggc atcagcccac gcgaggcgtt24480ggcgatggat ccgcagcagc ggttggtgct cgaaatcgcc tgggaagccc tcgaacgggc24540cggaatcgat ccgttgtcct tgaagggcag tggggtcggc acgtacatcg gtgctggaag24600ccgcgggtac gcgacggatg tgcggcagtt tcccgaggag gcggagggct acctcctgac24660gggtacctcc gccagtgtgc tgtcgggtcg ggtcgcgtac tcgtttggtt tcgagggtcc24720tgcggtgacg gtggacacgg cttgttcgtc gtcgttggtg gcgttgcact tggcgtgcca24780gtcgttgcgt tcgggtgagt gtgatctggc gttggccggt ggtgtgaccg taatgtcgac24840gccggagatg ttcgtggagt tctcccgtca gcgtggtttg gcgccggatg gccggtgcaa24900gtcgttcgcg gagagcgcgg acggcaccgg ctggggcgaa ggcgcgggcc tgttgttgct24960ggagcggttg tcggacgccc accggaatgg gcatcgggtg ttggcggtgg ttcgtgggtc25020tgcggtgaat caggacggcg catcgaacgg actggcggcg ccgaatggtc cgtcgcagca25080gcgggtgatc aaacaggcac tcgcgaatgc ggggctttcg gcgtctgatg tggacgccgt25140ggaggcccat ggaaccggga ccaggctggg tgatccgatc gaggcgcagg ccttgatcgc25200aacgtatggg cagggccggg agcgggatcg gccgttgtgg ttggggtcgg tcaagtcgaa25260catcggtcac acgcaggcgg cggcgggtgt tgccggtgtg atcaagatgg tgatgtccat25320gcggaacgac gagctgcccg ccacgctgca cgtgggtgcg cccacgtcgc aggtcgactg25380gtcggcgggg gcggtccggc tccttaccga acaggtacct tggccggagt ctgatcgcgt25440tcgtcgggtg ggggtgtctt cgttcgggat cagcggcacc aatgcacacg tgatcctcga25500acaatctacg aatgcgccag atagtcccgc ggccacggac aaatcaggat ccggatctac25560cgtggatatt ccggttgttc cctggttggt gtcgggacag acatcggatt ccctgcgggg25620acaggctgaa cgagtcttgt cccaggttga gtcccggccg gagcagcgtc cgctggatgt25680ggcctactcg cttgcttctg gccgagccgc gctggatgaa cgcgctgtcg tgctgggtgc25740ggaccggaat gagctggtag ctggattggt ggcgttggcc gccggtcatg aggcttccgg25800ggtgatcacc ggaactcgtg cttctgctcg gttcgggttc gtgttctcgg ggcagggcgg25860tcagtggttg gggatgggcc gggagctcta ctcgaagttt ccggtgttcg ctgctgcgtt25920tgatgaggct tgcgccgagt tggacgcaca tctgagtgaa gacctccggg tccgagatgt25980ggtcttcggt tccgatgcgc agctgctgga tcagacgttg tgggcgcagt cgggactgtt26040cgcgctgcaa gtcggcctct tggggctgct gggttcgtgg ggcgtccggc cggatgtggt26100gatggggcat tcggtcgggg agttggccgc cgcgtttgcg gctggagtgt tgtcgttgcg26160
ggatgcggct cggttggtgg ccgcacgcgc ccggttgatg caagccctgc cctctgacgg26220cgcgatgctc gcggtggccg ctggtgaaga cctgattcgg ccattgctgg ctggtcggga26280ggcatccgtg aacgtcgccg cgctcaatgc ccccggttcg gtggtgttgt cgggtgatcg26340ggatgtgctg gccgacatcg ccggccggct gaacgagctc ggagtccgga cgagacggtt26400gcgggtctcc catgcttttc attcgcaccg gatggacccg atgttgggcg agttcgccca26460gatcgcggag tctgcggagt tcggtaggcc aacgacaccg cttgtgtcga cgttgacggg26520tgagctcgac agagctgggg aaatgagcac gccagggtat tgggtgcgtc aggtgcgtga26580acccgtccgt ttcgccgacg gtgtccgggc cctggcagcg cagggcgtag acacggttgt26640tgagctcggc ccggacggag cgctgtccgc actggttcag gagtgtgcca ccgggtttga26700tcgggtcggg cggatttcgc ctgttcccct gatgcgcagg gagcgggacg agacccgttc26760ggtgatgaca gccctggcgc atcttcacac ccgtggcggt gagttggact ggcaggcgtt26820tttctccggc accggggcca ggcaggtcga gttgcccacg tatgccttcc aacgacggca26880ctactggatc gaatccagtg cgcggacagc acgcgaccgc gcagacatcg gcgaggtggc26940tgaacagttc tggaccgcgg ttgaacaagg cgatctggaa gcattggtct ccgcactgga27000gcttggggcg gacgacgaca catgcgcatc tttgagcgat gtactgccgg cgctgtcatc27060ctggcgaagc ggactccgca accgttcgct cgtcgattcc tgccggtacc gaatcaattg27120gcattcctct cgggaagcac cggccccgaa gatttccggt acctggctgt tggtcgtgcc27180cggcgatgcg gatgacggct tggccacggc tttgacgagt tcactggtcg aaggtggcgc27240cgaggtcgtc cggatcgacc tgtccgaaga ggacctgcac cgcgaggacc tcgcacagcg27300gctggccaat gcgctgacgg atgtcggtcg actcggtggc gtgctgtcgc tgttggggct27360cgatgactcg gctgttggag aattctcctg cttgacaagg ggtttcgcgt tgactgtgca27420gctggtgcgg gccttgcgca acgccgagct cgaggcgcct ttgtgggcgg tgacgcgcgg27480cggcgtctcg ttggaagacg taagtgtgtc tcctgagcag gccttgattt gggggctgct27540gcgtgttgcg ggcctggagc atccggagtt ctggggtggc ttgatcgacc tgccatcgga27600ttgggacgac cgattgggtg cgcggttggt gggtgtgttg gcggatggtg gcgaggatca27660agttgccatt cgtcgtggtg gtgtgttcgt gcggcggttg gaacgcgccg gtgcgtcggg27720tgccgggtcg gtgtggcgtc ctcgggggac ggtgttggtg acgggtggta cgggcggttt27780gggggcgcat gttgctcggt ggttggcggg tgccggggct gagcatgtgg tgttgaccag27840ccgtcgtggc gcggaggctc cgggcgctgg ggaattgcga gcggagctgg aggcgctggg27900tgctcgggtg tcgattgtgc cctgcgatgt ggctgatcgt gacgccgtgg ctggagtgtt27960
ggcagggatc ggcggggagt gtccgctgac tgcggtggtg cacgccgctg gggtcggcga28020ggcgggcggc gtggtggaga tggccttggc ggactttgca gaggtgttgt cggcgaaggt28080gcggggtgcg gcgaatctgg acgagttgct ggccgactcg gagttggatg cgtttgtgtt28140gttctcctcg gtgtcgggtg tgtggggtgc cgggggacaa ggtgcgtatg cggctgcgaa28200cgcctacttg gatgcgttgg ccgagcagcg tcgggcgagt gggttggccg ggaccgcggt28260tgcgtggggg ccgtgggcgg gtgacggcat ggccgcgggc gaaaccggcg cacagctgca28320tcgcatgggc ctggtgtcga tggaaccgag agcggctctg ctggcacttc agggcgcact28380ggaccgcgat gagacctccc tcgtcgtggc cgatgtcgac tgggcacggt tcgccccagc28440cttcacctcg gcacgtcggc gcccgctgct ggacaccatc gacgaggccc gagccgcatt28500ggaaaccacc agcgaaaaag cgggaacagg caaacccgtt gagctcaagc atcgcctggc28560cgggttgtca cggaaggaac gtgacgatgc ggtattggat ctggtgcggg cggaaacggc28620agctgtgctg ggacgcgacg atgccacggc cctggcgccg tcgcggccgt tccaggaact28680cggattcgac tccttgatgg cggtggagct gcgcaaccgg ctgaacaccg ccaccgggat28740ccagctgccc gccagcacga tcttcgacta ccccaatgcc gagtcgctgt cgcgtcacct28800ctgcgccggg cttttcccaa cagagacaac tgtggactcg gcccttgccg agctcgatcg28860aatcgagcag cagctctcga tgttcaccga ggaagcgcgg gcacgggacc gaatcgcgac28920acgactgcga gccctccacg cgaagtggaa cagcgcatct gaggcaccga ccggtgccga28980tgtcctgaac acactcgatt cggcaacgca cgacgagatc ttcgagttca tcgacaacga29040gctcgacctg tcctgagcag ttcctgcgga acgtccagtc gccgaaaccg ggtggaaatc29100acaatggcca atgaagaaaa gctcttcggc tatctgaaga aggtaactgc cgacctgcat29160cagacccggc agcgcctgct cgcagccgag agccggagtc aggagccgat cgtctccgcg29220agctgccggc tgcccggcgg cgtcgactct cccgaagcgc tttggcaact cgtgcgcact29280ggcactgacg ccatctcgga gttccccgcc gaccggggct gggatctcga ccggttgtac29340gatcctgacc cggaccacca gggaacctcg tacacgcggg ccggcggttt cctcgcagat29400gcgggcgatt tcgaccccgc catgttcggg atctcgccgc gtgaggcgtt ggcgatggac29460ccgcagcaac ggctgttgct ggagctgacc tgggaggccc tcgaacgggc gggaatagac29520ccgacatcgc tgcgcggcag caagaccggt gtcttcggcg gtgtcacgcc ccaggagtac29580gggccgccct tgccggagat gagccggaac tctggcggtt ttggactcac cgggcggatg29640gtgagtgtgg cgtcgggacg ggttgcgtat tcgtttggtt ttgagggtcc tgcggtgacg29700gtggatacgg cgtgttcgtc gtcgttggtg gcactgcatt tggcgtgtca gtcgttgcgt29760
tccggcgaat gtgatctagc gttggccggc ggtgtgacgg tgatggccac gccggcgacg29820ttcgtggagt tctcccgtca gcgtggtttg gcgccggatg ggcggtgtaa gtcgtttgcg29880gctgctgcgg atggcaccgg gtggggtgag ggtgccggtc tagtgttgtt ggagcgcttg29940tcggatgccc ggcgcaatgg gcacaaggtt ctggcggtgg tccgtggtag cgcggtgaac30000caggacggcg cgtcgaatgg tttgacggcg ccgaatggtc cgtcgcagca gcgggtgatc30060acccaggcgt tgtcaaatgc agggttgtcg gtgtccgatg tggatgcggt cgaggcgcat30120gggacgggca cgcggcttgg tgatccgatc gaggcacagg ccctgatcgc cacgtacggg30180cagggccggg agaaggatcg gccgttgtgg ttggggtcgg tcaagtccaa catcggtcac30240acgcaggcgg ccgctggcgt tgccggcgtc atcaagatgg tcttggcgat gcggcacggg30300cagcttcccg ccacgttgca tgtggatgat cccacgtcgg cggtggactg gtcggcgggt30360tcggtccggc ttctcacgga gaacacgccc tggccggaca gtggtcgtcc ttgtcgggtg30420ggagtgtcgt cgttcgggat cagcggcacc aatgcacatg tcattctcga acaatctcca30480gtcgagcagg gcgaaccgac cgggccggtc gaaggcgagc gggaaccgga ggcagccatc30540cccgtggtgc cgtggatggt gtcgggtaag acaccggagg ccgcgcgggc ccaggccgaa30600cgggtgcttt cgcatatcga ggaccggccg gagctgtcgc cggtggatgt ggcgtattcg30660ctaggcatga cgcgtgcggc gctggatgaa cgcgcagtga tgttgggctc ggaccgtgac30720acgctcctga ccgggttgag ggcgttcgcc gacggttgcg acgtgcccga agtggtgtcg30780ggatctgtgg ggaatggggg ccgcgtcggg tttgtgttcg ccggccaggg tgggcagtgg30840ccggggatgg gccgggggct ctactcggtg tttccgggtt tcgccgatgc gtttgacgag30900gcttgcgctg agttggatac acacctgggc caggaactgg gggttcggga tgtggtgttc30960ggttcggatg cgcggctggt ggatcggacg gtgtgggcgc agtcggggtt gttcgcgttg31020caggttggtt tgttgcggct gctgggttcg tggggtgttc ggcctgatgt ggtgttgggg31080cattcggtgg gtgagctggc tgcggtgcac gcggcgggtg tgttgtcgtt gccggaggcg31140gcgcggttgg tggcgggtcg tgcccggttg atgcaggcat tgccttctgg tggtgccatg31200ttggcggtgg ccgcgagtga ggcccaggtc gaaccgttgc tggatcgggt gcggggccgg31260gtcgagatcg cggcgatcaa cggtccggga tcggttgtgc tctctggcga ccgcgagctg31320ctcaccgaga tcgccgatcg gttgcacgat caggggtgtc ggacgcgatg gttgcgggtg31380tcgcacgctt tccattcgcc ccacatggag ccgatgctgg aagagttcgc ccagatcgcc31440cgaagccgtg agtatcaagc acccgaactg ccgatcatct cgaccctgac cggtgagctg31500gacggtggtc gagtgatggg cactcccgag tactgggtgc gtcaggtgcg tgagcccgtc31560
cgtttcgccg agggtgtcca ggcgcttgtc ggtcagggtg ccgacacgat tgtcgaattc31620ggtccggacg gggcgttgtc gacgttggtc gaggagtgtt tggcggaatc cgggcgggtg31680gccgggatcc cgctgatgcg caaggaccgc gacgaggcgc gaaccgtgct ggccgctttg31740gcgcagatcc acacccgtgg tggtgaggtg gaatggcagt cgtttttcgc cggcaccggg31800gcgaagcaag tcgagttgcc cacctacgct ttccagcggc agcgctactg gctggcatcc31860accggcggtg cgggtgacgt gaccgccgcg ggattggccg aggcggacca tccgttgctc31920ggtgcggtcg ttgcgttggc agacggcgaa ggtgtggtgc tgaccggtcg gctgacagcg31980gattcgcatc cgtggttgtc cgatcaccgg gtgctgggcg aaatcgtcgt ccccggcacc32040gcaatcgtcg agctggcgtg gcacgtcggc gagcgcctcg gttgtggccg ggtggaagaa32100ctggctttgg aagcgcccct gatcctgccg gatcatggag cggtccaggt tcaggtgctg32160gtgggaccgc ccggggaatc cggagcccgg tcggtggcgc tctactcccg ccctggagat32220gcgaccgaat ccgagtggaa gaagcacgcg acgggggtgc tgctgccacc cgtggccgcc32280gagaatcatg agctgcccgc ctggcccccg gagaatgcga ctgaaatcga tgccgacgag32340gtctacgaat tcctcgaagg gcacggtttc gcgtacggac cggcctttag atgtctgcgc32400ggtgcctggc gacgaggcgg ggaggtgttc gccgaagtcg cgttgccgga tggcatgcag32460gtgggggtgg atcgattcgg cgtccacccc gcgttgttgg acgcggttct gcatgccgcc32520gcggccgaga cgtccgtggt ccagagcgaa gcgcgggtgc cgttctcgtg gcgtggggtg32580gaacttcgcg ctaccgaaac cgcggtggtg cgggcacgca tctcgttgac cgcggatgac32640gagctgtcgt tggtcgcagt ggacccggtt ggcggattcg tggcctcggt cgattcgctg32700gtgacacgac cgatctcccg gcagcaggtg aggtctggcg cgatcggtga ttgcctgttc32760gaagtggagt ggcaccggag agcgttgttg gaaacagccg ccgacgacgg ccttgccatc32820gtcggtgacg gtgccagttg gccggaatcg gtgcgcgcaa ccgcacggtt cgcgaccctg32880gatgagctcc gttcggcggc ggactcggat gttcccgccc cgggtccggt gttggtcgca32940gctatgtcgg ccgaagaggt cgaaagtgaa tccctgccgt cgcgcgccca ggagtcgacc33000tccgatctgc tggctctcgt gcagtcgtgg cttgccgatg agcagttcgc cgaatcccag33060ctcgtggttg tcacgcgtgc agcggtgtcg gccgactcgg atacggacgt cgccgacctg33120gtgagtgcgt cgtcgtgggg gttgttgcgt tcagcccagt cggagaaccc gggtcgcttc33180gtactggtgg acgtggacgg cacaccagag tcgtggcagg cgttgccgac cgccgtgcga33240gcgggagaac cgcagctggc acttcggcgc ggcgtggcgc tggtgcctcg gttggcgcga33300ctcaaggcgc acggggaggg ctcctccccg cgactcgaca cggacgggac agtcctcatc33360
accggtggca ctggtgcgtt gggtggagtg gttgcccgtc acctggtggc ggagcacggg33420atccggcgtt tggttttggc aggccggcgt ggctggaacg cgcctggagt ccacgatttg33480gtggatgagc tggcgcgctc gggcgctgtg gttgacgtgg tggcttgcga tgtgggtaac33540cggacagatc tggagcaggc gctggccgcc attccggtcg accgcccgtt gcgggggatc33600gtgcataccg ctggggtgtt ggccgacgga gtgctcgggt ccttgtcggc ggcggatgtg33660gacacggtgt tcgccccgaa ggtggcgggg gcgtggcatc tgcatgagtt gacccgcgag33720ctggatctgt cgttcttcgt tcttttctcg tccttctcgg ggattgcggg tgccgcgggg33780caggccaact acgcggcggc gaacacgttc ctggatgcat tggcaggtta tcgccgcgcg33840cgtggactac ccgggttgtc gttggcatgg ggactgtggg cgcaacccgg cggtatgacg33900agtggcttgg acgcggcgtc ggtggagcgg ttggcgcgga cgggcatagc agaacattcc33960acggaggatg gactccgcct gttcgatgcc gcgattgcga aggacagggc ttgcgtcgtt34020cccgctcgat tggacagggc gctgctggtc gagcacgcac ggtcgcacgc gattccagca34080ctgatgaccg cgttggctcc tgctcgtggc ggtgtggcga ggagagcaac caactctcag34140gccgcggatg aggacgcgct gttgggtttg gtgcgggacc acgtctcggc ggtactgggc34200tattcgggtg cggtcgaggt tgggggcgac cgtgctttcc gtgatctagg ttttgattcg34260ttgtctggag tggagttgcg gaaccgcctg gccggggtgc tgggggtgcg gttgccggcg34320actgcggtgt tcgattaccc gacgccgcgg gcgctggcgc gtttcttgca tcaggaattg34380gcaggcgagg tcgggtcgat gtcgacgccg gtgaccaggg cagcgagcgt cgaagaggat34440cttattgcga ttgtcgggat ggggtgtcgt tttccgggtg gggtgtcgtc gccggaggag34500ctttggcggt tggtggccgg gggcgtggat gcggtggctg ggttcccgga cgatcgcggc34560tgggatctgg cggggttgtt cgatccggat cccgatcatc tcggcacttc gtacgtatgt34620gagggcgggt ttctgcggga cgcggcggag ttcgatgccg acatgttcgg cgtcagcccg34680cgtgaggcgt tggcgatgga tccgcagcag cggttgctgc tggaggtcgc ttgggaaacc34740ctggagcggg ctgggatcga tccgttctcg ttgcacggca gccggaccgg tgtgttcgcg34800ggcttgatgt accacgacta cggggcccga ttcatcacca gagcaccgga gggcttcgaa34860gggcacctcg ggacgggtaa tgcggggagc gtgctgtcgg gtcgggttgc gtactcgttt34920ggttttgagg gtcctgcggt gacggtggat actgcgtgtt cgtcgtcgtt ggtggcgttg34980cacctggcgg gtcaagcact gcgggccggt gagtgcgaac tcgcccttgc cggtggcgtc35040acggtgatgt cgacgccgac gacgttcgtg gagttctccc gtcaacgggg actggctccg35100gatgggcggt gcaagtcgtt cgcggcggcc gcggatggca ccggttgggg agaaggcgcg35160
ggcctggtgt tgctggagag gttgtcggat gcccggcgca acggacacaa ggtcctggcg35220gtggttcgtg gtagcgcggt gaaccaggac ggcgcgtcga atggtttgac cgcgccaaat35280ggcccgtcac agcaaagggt gatcacccag gcactcacga gtgccgggct gtccctgtcc35340gacgtggatg ctgtggaggc gcatgggacg ggcacgcggc taggtgatcc gatcgaggca35400caggcgttga tcgctacgta tggccgagat cgtgatcccg gtcggccgct gtggttgggg35460tcggtgaagt cgaatattgg tcatacccag gcggcagcgg gtgtggctgg tgtgatcaag35520atggtgatgg cgatgcggca tggggagctg ccgcgcacgt tgcacgtgga cgagccctcc35580gcgcaggtgg actggtctgc gggcacggtc caactcctca cggagaacac gccctggccc35640gacagcggtc gtcttcgtcg ggccggcgtg tcatcgttcg ggatcagcgg caccaacgcg35700cacctgatcc ttgaacaacc tccgcgagag acgcatcgcg caacagagcc ggattcgagt35760tctgtcctcg atgttccggt ggtgccgtgg atggtgtcgg gcaaaacacc cgaagcgcta35820tccgcccagg cagatgcact gatgtcctac ttgaacaatc gcgttgatgt ttctccacga35880gatatcgggt attcacttgc ggtgacccgt ccggcgttgg accaccgggc tgtcgtgctg35940ggtgcggatc gtgaagcgtt gctgccgggg ttgaaagcgc tggctgccag tcatgacgcc36000gctgaggtga tcacaggcac tcgtgccgct gggccggtcg gattcgtgtt ctccggtcaa36060ggtggtcagt ggcccgggat gggaagcggg ctctactcgg cgtttccggt gttcgccgac36120gcgtttgatg aagcctgcgg cgagctggat gcgcatctcg ggcagaaagc acgggttcga36180gacgtgatgt ccggttcgga taagcaactt ctggatcaga ctttgtgggc gcagtcgggc36240ctgtttgcgt tgcaagtcgg gctctgggag ttgttgggtt cgtggggtgt ccgacccggt36300gtggtgctgg gccattcggt cggtgagctg gcggcggcgt ttgcggctgg agtgttggcg36360ttgccggatg cggctcggtt ggtggcaggc cgtgcccggt tgatgcaagc cctgccacct36420ggcggtgcca tgctcgcggc ggctgctgga gagaaggagc tgcggccgtt gttggccgac36480cgggctgatc gtgtggggat cgccgcggtc aacgcacccg agtcggtggt gctctccggt36540gatcgggatg cgctcgatga catcgccggc cgactggacg ggcaaggggt ccggtcgagg36600tggttgcggg tttcgcatgc gtttcattcg catcggatgg atccgatgct ggaggagttc36660gccgaaatcg cacggagcgt ggactaccgg tcgccagggc tgccggctgt gtcgacgttg36720acgggtgagc tcgatgaggt cggcatgatg gctacgccgg agtattgggt gcgtcaggtg36780cgagaacccg tccgcttcgc cgacggtgtt gctgctctcg cggctcacgg tgtgagcagc36840atcgtcgagg tcggtccgga cggggtgttg tcggcgctgg tgcaggagtg tgcggccgga36900tccgatcagg gcggacgggt ggccgcggtt ccactcatgc gcagcaattg cgacgaggcg36960
caaaaggtga taacggcctt ggcgcaggtc catgcgcgtg gtgctgaggt ggactggcgg37020tcgtttttcg ccggtaccgg ggcaaagcag gtcgagctgc ccacgtatgc cttccaacga37080cagcggtact ggcttgactc gccatccgaa ccggtcgggc aatccgccga tctcgcgccc37140cagtcgggct tctgggaact cgtcgagcag gaagatgtca gcgcgcttag cgccgccctg37200aatataaccg gcgatcccga cgtgcaggcg tccctggaat cggtggttcc ggtcctctcc37260tcctggcatc gccggatccg caacgaatcc ctggtgcacc agtggcggta ccgcatttcc37320tggcatgagc gggcagatct gccagaccgg tcgttgtcgg ggacatggct cgtcgtcgtg37380ccggagggtt ggtctacgag tcagcaagtt ctgcgtttcc gcgagatgtt cgaggaacgg37440ggttgcgcgg cggttttgtt cgagctcgcc gggcacgacg aggaagccct ggtgcaacga37500ttccgctcgt tgcctgtcgc gtcaggggga ataagcggcg tgctgtcctt gctggcgctg37560gatgaatcgc cgtcctcgtc gaacgctgcc ttgccgaatg gtgcgctgaa ctcattggta37620ctgctgcgag ctctgcggac cgcggatgtg ccggcgccat tgtggttggc gacgtgtggt37680ggggtggcgg taggggatgt gccggtgaat ccggggcagg cgctgatgtg gggactgggc37740cgcgtcgtcg gcctggaaaa tccggactgg tggggcggcc tggtcgacgt gccggacttg37800ctcgataagg acgctcaaga acgcttgtcg gtcgtgttgg ctggtcttgg cgaggacgag37860atcgcggtgc gccccgatgg cgtgttcgtg cggcggttgg aacgcgctga tttgccggat37920atggggtcgg catggcgtcc tcggggcacc gtgttggtga cgggtggtac gggcggtttg37980ggggcgcatg ttgctcggtg gctggcgggt gccggggccg agcatgtggt gttgaccagc38040cgtcgtggcg cggaggctcc gggcgctgga gatttgcgag cggagctgga ggcgctgggc38100gctcgggtgt cgatcagatc ctgcgatgtg gcagatcgtg acgctttggc cgaagtgttg38160gcgaccattc cggatgattg cccgctgacc gcggtgatgc atgcggcggg ggtcgttgaa38220gtcggcgacg tggcgtcgat gtgtctgacc gacttcattg gggtgctgtc ggcgaaggtg38280ggtggtgcgg cgaatctcga tgagttgctc gccgacgtcg agctggatgc cttcgtgctg38340ttctcctcgg tatcgggtgt gtggggtgct ggggggcagg gcgcttatgc ggcggcgaac38400gcctacttgg atgcgttggc gcagcagcgt cgggcaaggg gcttggccgg gactgcggtt38460gcgtgggggc cgtgggccgg tgacggcatg gccgcaggtg aaggcggcgc acagctgcgc38520cgtaccggcc tggtgccaat ggctgcggat cgcgcgttgc tggcacttca gggtgcattg38580gatcgagacg agacatccct ggtcgtagcc gatatggcat gggagaggtt cgccccggtg38640ttcgccatgt cccgtcggcg tccgctgctc gacgagctgc ccgaagcaca gcaggcgttg38700gcggatgcgg agaacaccac gggtgcggcg gactcggccg gcccgctgca gcggatcgtg38760
ggcatggcag ccgccgaacg ccgccgggcg atgatggaac tggtgctggc ggagacctcg38820attgtgttgg ggcacaacgg gtcggatgca gtgagtcccg accgggcgtt ccaggagctc38880ggattcgatt cgctgatggc cgtcgaactg cgcaacaggc tgggcgaggc aacaggattg38940agtctgccga ccacgttgat cttcgattat ccgagcccat ccgctctggc ggagcagctg39000gtcggcgagc tggtgggagc gcagcccgcg accaccgtcg tggccggggc cgatccagtg39060gatgatccgg ttgtcgtggt cgcgatggga tgccggtatc cgggcgatgt ctgctcgcct39120gaggagctgt ggcagctggt ttccgcggga cgtgatgcgg tttcgacgtt ccccaccgat39180cggggttggg actgcgacgc gttgttcgac ccggatccgg atcgggcagg ccgtacctac39240gtgcgagaag gtgccttcct gaccggtgct gatcggttcg atgcggggtt cttcggcatc39300agccctcgcg aggcgcgagc aatggatccg cagcagaggt tgttgctcga ggtggcgtgg39360gaggttttcg aacgagcggg gatcgctccg ctgtcgttgc ggggcagcag gaccggtgtg39420ttcgcgggca ccaatggaca ggaccacggt gcgaaagtgg ctgccgcgcc ggaggcggcg39480ggtcacctcc tgaccggaaa cgccgcgagt gtcatggccg gccggatttc ctacacgttc39540ggcctcgagg gtcctgcggt ggcggtggat accgcgtgtt cgtcgtcatt ggtggcgttg39600catttggcgt gccagtcgct gcgttcgggt gagtgtgata tggcgttggc gggtggtgtg39660acggtgatgt cgacacccct ggcgttcctc gaattctctc gtcagcgcgg tttggcgccc39720gatggccggt gtaagtcgtt tgcggctgcg gcggatggca ccgggtgggg tgagggcgcc39780ggcctggttc tgctggagcg gttgtcggat gcgcgtcgta atggtcaccg ggtgttagcc39840gtggttcgcg ggtctgcggt gaatcaggat ggtgcgtcga atggcttgac ggcgccgaat39900ggcccgtcgc agcagcgggt gatccggcag gccctcgcga atgcgggact gtcggcgtcc39960gatgtggatg tcgtggaggc gcacgggacc ggcaccgggc tcggggatcc gatcgaggcg40020caggcactga tcgcggcata tgggcaggga cgggatcctg aacgggccct gtggttgggg40080tcgatcaagt ccaacatcgg ccacacgcag gcagcggccg gtgtggctgg ggtcatcaag40140atggtgcagg ccatgcggca tggggagttg cctgccacgt tgcacgtgga caaacccact40200ccgcaggtcg actggtctgc cggggccgtt cggctcctca ccgggaacac gccctggccc40260gagagcggcc gtcctcgtcg agctggggtg tcgtcgttcg ggatcagcgg caccaacgca40320cacctcatcc tcgaacaacc gccgtcggaa ccagcggaga tcgaccgttc gaatcggcgg40380gtcactgcgc atccggcggt gatcccgtgg atgttgtcgg ccaggagtct cacagcgctg40440caggcccagg cggctgcgct gcagggccgg ctggaccggg tgcctggcgc ttctccgctg40500gatttggggt attcactcgc gaccactcgt tctgtgctgg acgagcgcgc cgtcgtgtgg40560
ggtgccgatc gggagaccct gttgtcgagg ctggcagcgc tggccgatgg ccggactgcg40620ccgggggtgg tcaccggcgc tgcgaattcc ggtggccgca tcggattcgt tttttccggt40680cagggcagtc agtggctggg gatgggaaag gcgttgtgcg cggctttccc ggcgttcgca40740gacgccttcg aggaagcctg cgacgcgctg ggcgcgcact tgggcgcgca cttgggcgcg40800gacttgggcg tggacgtccg gggcgtgctg ttcggtgctg atgagcaggt gctcgaccgg40860acgttgtggg cgcagccggg gatcttcgcg gttcaggtcg gcctcctggg attgctgagg40920tcgtggggcg tgcggccaga cgcggtgctg gggcactcgg tcggcgagtt ggctgcggcg40980cacgcggctg gtgtgttgtc cttgccggac gcggcacggt tggttgcggc ccgggccagc41040ctgatgcagg cattgcccac cggcggcgca atgctcgcgg tcgccaccag cgaggcggcg41100gtcgaaccgc tgcttgccgg gatgtgcgat cgggtcagca tcgctgcgat caacggcccg41160gagtcggtag tgctctccgg cgaccgcgac gtgctcgcag aggtcgccgg cgaactcgat41220gcccgagggc ttaggaccaa atggttgcgg gtctcccacg ctttccactc gcaccggatg41280caaccgattc tggacgagta cgccgaaacc gccgggtgcg tcgagttcgg tgaaccggtg41340gtgccgatcg tctccgccgc gaccggtgcg ctggacaccg ccggactgat gtgcgcagcc41400ggctactggg tgcgccaggt gcgtgatccc gtccgcttcg gagacggtgt ccaagcgctc41460gtggaccaag gcgtggacac gatcgtcgag ttcggcccgg acggggcgtt gtcggccttg41520gtccagcagt gcttggccgg gtccgaccag gccgggaggg tggcggcgat cccgctgatg41580cgcagggacc gcgatgaggt cgagaccgcg gtggctgccc tggcgcacgt gcatgtccgc41640ggcggtgcgg tggactggtc ggcttgcttc gccggcacgg gcgctcgcac cgtcgagttg41700cccacctacg ccttccagcg gcagcggtac tggctggccg ggcaagcgga cgggcgtggc41760ggcgatgtgg ttgccgaccc ggtcaacgcg cgcttctggg agttggtcga gcgcgccgat41820ccggaaccgt tggtggatga gctctgcatc gaccgggacc agcccttcag ggaggtgctg41880cccgtgctgg cttcctggcg cgagaaacaa cgccagaagg ccgtcacgga ttcttggcgc41940taccaggtgc ggtggaggtc cgtcgaggtg cagtccgcag ccagcctccg gggcgtgtgg42000ctggtggtgc ttccagctga cggactccga gatcaaccgg cggccgtcat cgacgcgctg42060atcgcgcgcg gcgccgaggt cgcggtcctg gaattgaccg agcaggactt ccaacgcggt42120gcgcttgtgg acaaggtgcg cgccgtcatt gccgaccgca ccgaggtgac gggtgtgctg42180tctctgttgg caatggacgg aatgccctgc gcagagcatc cgcacctgtc ccgtggtgtc42240gccgctaccg tgatcctgac gcaggtgttg ggcgatgcgg gcgtttccgc cccgctgtgg42300ctggccacga ctggtggcgt cgaggtcggg accgaggacg gtccggccga tccggaccac42360
ggcttgatct gggggctcgg cagggtcgtc ggccttgaac atccgcagcg gtggggtggc42420ctgatcgacc ttccggcgac actggacgag acgtcccgga acgggttggt ggccgcgctc42480gccgggacgg cggccgaaga tcagctcgcc gtgcgttcat ccgggttgtt cgttcgcaga42540gtggtgcgcg cagcgcagaa ttcccgttca gggacatggc gtagccgggg aacggtcctc42600atcacgggcg gaacaggcgc gctcggtgcc gaggtcgcac gatggctggc ccggcggggt42660gctgagcatc tggtgttgat cagtcgccgc ggtccggaag ctcccggcgc cgcggacctg42720caggccgagc tgaccgagct cggcgtgaaa gtcacagtcg tggcctgtga tgtgacggac42780ggcgacgaac tgagggcggt gctggcggcc gttccgacgg agcatccgct gtcggcggta42840gtgcacaccg ccggcgtcgg gacgcctgcg aacctggccg agacgacctt ggcgcagttc42900gccgacgtgt tgtcggccaa ggtcgtcggc gcggcgaacc tggaccggct gcttggtggg42960caaccgttgg acgccttcgt gctgttctcc tcgatctcgg gggtttgggg agccggcggc43020caaggagcct attcggccgc caatgcgtat ctcgatgccc ttgccgagcg ccgacgggct43080tgcggtcggc cggcgacgtg cgtcgcctgg ggtccgtggg ccggtgcggg catggccgtt43140caggaaggca acgaggcgca tctccgccga aggggcctgg taccgatgga accgcagtcg43200gccctctccg cgctgcaaca ggccctgtcc cgacgagaaa ccgccatcac cgtcgcagat43260gtggactggg aacgattcgc cgccactttc accgcggccc gcccgcggcc actattggat43320gagatcgtgg atctacggcc caacaccgag actgcggaga agcacggtgc cggcgagctg43380gggcagcagc tggccgcact gccggccgct gagcgcggac atctgctgct ggaggtggtg43440ctggcggaaa ccgccaacac cctggggcac gattcggcgg aggctgtgca acccgatcgg43500accttcgccg aactgggctt cgattcgctt accgcggtag agctgcgcaa caggttgaac43560gcggtgaccg ggcttcgcct gccgccgacg ctggttttcg accacccgac accgctggcg43620gtgtccgaac agttggttcc ggcgttggtc gcggagccgg gcgatggcat cgagtcgttg43680ctcgcggagc tcgacaggct ggataccacg ttggcgcaac gaccttcgat cccaccggaa43740gaccaggcca aggtggcgga gcgcttgcag gcactcatcg ccaagtggga cggggcgcgt43800gatggcacgg ccaaagtgac gtcaccccaa tcgctgacgg cggccacgga cgacgaaatc43860ttcgacctca tcgaccggaa gttccggcgc tgaccgcctt cttcctcgcc tcagctcccc43920tgatcactgg aacggtgtat ttcgatggcc aatgaagaaa agctccgcga gtacctcaag43980cgtgtcgtcg tcgaactgga ggaggcgcac gaacgcctgc acgagttgga gcgccaggag44040cacgacccca tcgcgatcgt gtcgatggga tgccgttatc ccggtggcgt ctccactccg44100gaggagctgt ggcgactggt cgtcgacgga ggagacgcga tcgcgaactt ccccgaagac44160
cgtggctgga acctgggcga gctgttcgat cctgatccgg gtcgagccgg gacctcctac44220gtccgcgagg gtggtttcct gcgcggagtc gcggacttcg atgccgggct cttcgggatc44280agtccgcgcg aggcgcaggc gatggacccg caacagcggt tgctgctgga gatctcgtgg44340gaagtgctcg agcgcgccgg tatcgacccg ttttccttgc ggggcaccaa gaccagtgtg44400tttgcgggcc tgatttacca cgactacgcg tcgcggttca gcaagacccc agccgagttc44460gagggttact tcgccaccgg gaacgcgggc agcgtcgcat ccggccgggt ggcttacacc44520ttcggattgg agggcccggc ggtcaccgtg gacaccgcct gctcgtcgtc cctggtggcg44580ttgcacctgg cctgccagtc cctgcggctg ggcgaatgcg acctggccct ggccggtggc44640atttcggtga tggccacgcc gggagccttc gtcgagttca gccggcaacg cgcactcgcc44700tcggatggcc ggtgcaagcc cttcgcggat gccgcggacg gcacgggctg gggcgagggc44760gccggaatgc tgctgctgga acggctgtcg gacgcacggc gaaacggcca cccggtgctg44820gcggcggtag tcggttccgc gatcaaccag gacgggatgt ccaacggcct gaccgcgccc44880agcggtcccg cacagcagcg agtgatccgc caggccctga cgaacgccgg gttgtcgccc44940gccgaggtcg atgtggtcga ggcgcacggt acgggcacgg ccttgggcga cccgatcgag45000gcgcgggccc tgatcgccac ctacggggcg aaccggtcgg cggatcaccc gctgctgctg45060ggttccctca agtcgaacat cggccacacc caggctgccg ccggtgtggc cggggtgatc45120aagtcggtca tggccatcag gcaccgggag atgccccgca gcctgcacat cgaccagccc45180tcgcggcacg tggactggtc ggcgggcgcg gtgcggctgc tcacggacag cgttgactgg45240gcggatcccg gccggccgcg ccgagcaggg gtgtcctcgt tcggcatgag cggtaccaac45300gcacacctga tcgtcgagga agtatccgac gagccggtct cgggcagtac cgagccgacc45360ggggcacttc cctggccgct gtccggcaag acggagaccg cattgcgcga gcaggctgcc45420gagctgctct ccgccgtgac cgcgcacccg gagccgggtc tggggaacgt cgggtactcg45480ctggccaccg gtcgcgctgc gatggagcac cgggctgtcg tggttgccga ggatcgggac45540tccttcgtcg ccggactgac ggcgttggct gcgggcgttc cggcagccaa cgtggtgcaa45600ggggcggccg actgcaaagg aaaggtcgcg ttcgtgttcc ccggccaggg ctcgcattgg45660caggggatgg cgagggaact gttcgaatcc tcgccggtgt tccggcggaa gctggaggaa45720tgcgcggcgg ctacggcccc ctacgtggac tggtcgctgc tcggcgtcct tcgcggtgat45780cccgatgcac ccgcactgga tcgcgacgac gtgattcagt tcgcgctgtt cgccatgatg45840gtgtcgctgg cagaactgtg gcgttcgtgc ggagtggagc ccgccgcggt ggtcggtcac45900tcccagggcg agatcgccgc cgcccatgtg gcgggggctt tgtccttgac ggatgcggtg45960
cgcatcgtcg ctgcccgctg caatgcggtg tcggtgcttg cagggaaagg aggcatgctc46020gcgatcgcct tgccggaaag cgcagtggtg aagcgaatcg caggcctgcc agagttgacc46080gttgcagcgg tcaacggacc cggctccact gtcgtttccg gcgaaccgtc cgctctggag46140cgtttgcaga ccgaactgtc cgcggagaac gtgcaggctc ggcgggtgcg aattgattac46200gcctcgcact cggcgcagat cgcacaggtc cagggccggc ttctggaccg gctgggcgag46260gtcgggtccg aacctgctga gatcgctttc tactcgacgg tgaccggcga gcggacggac46320accggccggc ttgacgcgga ctactggtac cagaaccttc ggcagcccgt ccggttccag46380cagaccgtcg cccggatggc agatcagggc tatcggttct tcgtcgaggt gagcccgcac46440ccgctgctca ccgcgggaat ccaggaaacg ctggaagccg cggacgcgga cgcgggcggg46500gtggtggtcg gttcgctgcg gggtggcgag ggcggctccc ggcgctggct gacttcgctg46560gccgagtgcc aggtgcgcgg actaccggtg aattgggaac aggtattcct cgacaccgga46620gcccgacgcg tgccgctgcc gacatacccg ttccagcggc agcggtactg gttggagtcc46680gccgagtacg acgcgggcga tctcggttcg gtgggcttgc gctccgcgga gcatcccctg46740ctcggggctg cggtgacact ggccgatgcg ggcgggttcc tgctgaccgg caagctgtcg46800gtcaagaccc agccctggtt ggccgaccac gcggtccgtg gggcgatcct gctgcccggc46860accgccttcg tggaaatgct gatacgcgcc gcggaccagg tcgggtgcga tctgatcgag46920gagttgtccc tgacgactcc gctggttctg cccgcgaccg gtgcggtgca ggtgcagatc46980gcggttggcg gtccggacga ggccgggcgc cgctcggtcc gcgtgcattc ctgtcgggac47040gactccgtgc cgcaggactc gtggacctgc cacgcgaccg gcacgttgac caccagtgag47100caccgggacg ccggccaggc ccgcgatggg atttggccgc cgaacgatgc tgtcgcggtt47160ccactggaca gcttttacgc gcgcgcagct gagcggggct tcgatttcgg tccggcgttc47220caggggttgc aggcggtttg gaaacgcgga gacgagatct tcgccgaggt cggcctgccc47280gcagcacagc gcgaggacgc cggcaggttc ggagtccacc cggctctgct ggatgcggca47340ctgcaggcgc tgggcgcagc cgaggaggat ccggacgagg gatggctccc cttcgcgtgg47400caaggtgtgt ccctcaaggc gaccggcgcg ctttcgcttc gggtgcacat cgtcccggcg47460ggtgcgaacg cggtgtcggt gttcacgacc gacgcgacgg gccaagccgt gctctccatc47520gactcgctgg tgctgcgcaa gatttcggac gagcagttgg cagcggtccg tgcgatggac47580cacgagtccc tgttccgggt cgactggagg cgaatctcgc ccggcgctgc caagccggtc47640tcctgggcag tgatcggcaa tgacgaactc gctcgagcct gcggctcggc acttggcacg47700gaactccacc ccgacctgac cgggttggct gacccgcccc cggacgtggt ggtggtgcca47760
tgcggtgcgt ttcaccagga cttggaggtt gcttccgagg cacgtgccgc aacgcaacgc47820gtgcttgacc tgatccaggg ttggttggcg gcggagcgat tcgccggatc tcgcctggtg47880gtggtgacgt gtggtgcggt gtcgaccggg cccgccgagg gtgtttccga cctggtgcat47940gctgcgtcgt ggggcttgtt gcgttcagcg cagtcggaga acccgaatcg attcgtgttg48000gtcgatgtgg acgcaaccgc cgagtcatgg cgcgcgctcg cggcggcggt gcgttccgga48060gaaccgcagc tagcgctgcg cgccggcgaa gtccgagtgc ctcgcctgac acgatgtgtt48120gccgccgagg acagccggat cccagtgcct ggtgcggatg ggacggtgtt gatttccggc48180ggtacgggcc tgctgggcgg gttggtagcc cggcatttgg tggcggagcg cggtgtccgc48240cgcctggtgc tggcagggcg acgcggctgg agcgcccccg gggtcaccga attggtggat48300gagctggtgg gcctgggagc tgtggtcgag gtggcgagct gtgatgtcgg ggaccgggcc48360cagctggacc ggctgctgac gacgatctcg gcagagttcc cgctgcgcgg agtggtgcat48420gcggccgggg cactggccga cggggtcgtc gagtcgttga caccagagca cgtggcaaag48480gtgttcgggc cgaaggtcgc cggtgcgtgg cacctgcacg agctgacccg tgaactggat48540ctctcgttct tcgtgctctt ctcctcgttc tccggggtgg tgggggctgc gggtcaagga48600aactacgcgg cggcgaacgc gttcctggac ggcctggctc agcaccggcg gacggcggga48660ctgcctgcgg tgtcgctggc ttggggcttg tgggagccga ccagcgggat gaccggagcg48720ctcgatgcgg cggaccgcag ccgcatttcg cgcaccaatc cgccgatgtc cgcggaggac48780gggttgcggc tgttcgagat ggcgtttcat gttccgggcg aatcgcttct ggtcccggtc48840cacatcgacc tgaacgccct gcgcgccgat gcggccgacg gcggtgtgcc tgcgttgttg48900cacgacctgg tgcccgcgcc cgtgcggcgg agcgcggtca acgagtcgga ggatgtcacc48960ggtctggtcg gtcggctgcg gaggcttccg gacctggatc aggaaaccct gctgttgggt49020ttggtgcggg agcatgtttc ggctgtgctg gggtattcgg gtgcggtcga ggttggggtc49080gagcgtgctt tccgggattt gggttttgat tcgttgtccg gtgtggagtt gcggaaccgg49140cttggcgggg tgctgggcgt tcggttgccg gctactgcgg tgttcgacta tccgacaccg49200cgggccttgg ttcggttctt gcgcgacaaa ctgattggtg gcgtggaggc acgcaattcg49260gcaccggcgg ttgtggaggc ggccagtggt gacgacccgg ttgtgatcgt ggggatgggg49320tgtcgttttc cgggtggggt gtcctcgccg gaggagcttt ggcgtttggt ggccgggggc49380ttggatgcgg tggcggagtt ccccgacgat cgtggttggg atcaggcggg gttgttcgat49440ccggatcccg atcgtctcgg gacttcgtat gtgtgtgagg gcggcttcct gcgagatgcg49500gcggagttcg atgccggttt cttcgggatt tccccgcgtg aggcgttggc gatggatccg49560
cagcagcggt tgttgctgga gatcgcttgg gagaccttgg agcgggcggg gattgatccg49620ctttcgttgc gagggagtcg gaccggcgtg ttcgcggggc tgatgcacca cgactacggc49680gcgcggttcg tcaccagggc gccggagggt ttcgagggtt atctaggtaa tggcagcgcg49740ggcggcgtct tttcgggtcg ggtcgcgtat tcgtttggtt tcgagggtcc tgcggtgacg49800gtggatacgg cgtgttcgtc gtcgttggtg tccatgcacc tggcgggtca agcactgcgg49860tctggtgagt gtgatctggc tcttgcgggt ggtgtgacgg tgatggccac gccggggatg49920ttcgtggagt tttcgcgcca gaggggtttg gcggcggacg ggcggtgtaa gtcgtttgcg49980gctgctgcgg atggcaccgg ctggggcgaa ggcgcgggcc tggtgttgtt ggagcggctg50040tcggatgccc ggcgcaacgg gcacgcggtt ctggcggtcg tgcggggtag cgcggtgaat50100caggatggtg cgtcgaatgg tttgacggcg ccgaatggtc cgtcgcagca gcgggtgatc50160acgcaggcgt tggcgagtgc gggtctgtcg gtgtctgatg tggacgctgt ggaggcgcat50220gggactggga ccaggcttgg tgatccgatt gaggcgcagg cactgattgc cacttacggg50280caggagcggg atagggatcg gccgttgtgg ttggggtcgg tgaagtcgaa tattggtcat50340acgcaggcgg cagcgggtgt tgctggtgtg atcaagatgg tgatggcgat gcggcacgag50400cagctgcccg ccacgttgca tgtggatgaa cctacgccgg aagtggattg gtcggcgggg50460gaggtccagc tccttacgga gaacacgccc tggcccgaca gcggccatcc tcgtcgggcg50520ggagtgtcgt cgttcggcat cagcggcacc aacgcacatg tcatcctcga acaagcctcg50580aatacaccag acgagattgc gcagagcaac ggtcccgaat cggaatctac cgtggacatc50640ccagcggtcc cgttgatcgt gtcgggcaga acaccggaag cgctcagcgc tcaggcgagc50700gcattgatgt cctatttgga taatcgtccc gatatttcat cccttgatgc cgcgttttcg50760ttggcttctt cccgggccgc gttggaggag cgggcggtcg tgctgggagc ggaccgtgaa50820gcgctgttgt ctgggttgga agcgctggct gccggtcgcg acgcttctgg ggtggtgtcg50880ggatccctga tctctggcgg ggttgggttt gtgttttccg gtcagggtgg tcagtggctg50940gggatgggaa gagggctcta ctcggcgttt ccggtgttcg ctgacgcgtt tgacgaagct51000tgtgccggac tggatgcgca tctggggcag caggtggggg ttcgggatgt ggtgttcggt51060tccgacgggt ccttgctgga tcggacgttg tgggcgcagt cgggtttgtt cgcgttgcag51120gttggtttgc tgaggctgct gggctcgtgg ggtgttcggc ctggtgtggt gatggggcat51180tcggtgggtg agtttgcggc ggcgtttgcg gcgggtgtgt tgtcgttgcc ggatgcggct51240cggttggtgg cgggtcgtgc ccggttgatg caggcgttgc cggatggcgg tgccatgttg51300gcggtggctg ctggcgagga gcagctgcgg ccgttgttgg ccgctcgggg tgaaggggtg51360
gggatcgccg cggtcaacgc ttctgagtcg gtggtgctct ccggcgatcg ggaggtgctt51420gaggacattg ccggcgggct ggatgggcaa ggggttcggt ggcggtggtt gcgggtttcg51480catgcgtttc attcgtatcg gatggacccg atgctgcagg agttcacaga tatcgcaggc51540agcgtggact accggcgttg cgacctgccg gtcgtgtcga cgttgacggg tgagctcgac51600accgctggca tgctggctac accagggtat tgggtgcgtc aggtgcgtga gcccgtccgc51660ttcgccgacg gggttcgggc gctcgcgcag cagggggtcg gcacgatctt cgagcttggc51720cctgatgcga ttctgtcggc tctgattcct gattgtcatt cctggggtga tcagactgtg51780ccgattccgt tgctgcgcaa ggaccgcgct gaacccgaaa ctgtggtcgc cgcggtggcg51840cgggcgcaca cgcgtggtgt tcaggtcgat tggtcggcgt ttttcgctgg taccggggct51900gggcgggtcg agttgccgac gtatgccttc cagcggcagc ggtattggct ggagtcatcg51960gtttccggtg atgtgacagg tatcggtctg gctggggcgg agcatccgtt gctgggggcc52020gtggttgtgt tggccgacgg tgatgggatg gtgttgaccg gtcggttgtc ggtggggacg52080catcggtggc tggccgagca tcgtgtgctg ggggaggtcg tggttcccgg cacggctatc52140ctggagatgg tcttgcatgc gggggcgcgg gttggttgtg gccgggtgga ggagctcacc52200ctggaagcac cgctggtggt gcccgaacgc gatgccatcg aaatccagct gctggtgaac52260gcgcccgacg acaagggtcg gcggtccgtg tcgctgcatt cccgcccggc cggtgggtct52320gggggtgggg gttggacgcg gcacgccacg ggcgaactcg tcgtcgccgg cacgggtggt52380ggggcggtta ctggttggtc gactgagggt gccgagccgg ttgctctcgg tgagttttat52440gtcgttcagg cggggaacgg gttcgagtat gggccgttgt tccaggggct tcgggcggcg52500tggcgtcgtg gtggcgaggt tctcgcggag gtcgccctgc cggcagcggc tggtgcgatg52560gcggggttct tgatcaatcc ggcgttgctg gatgccgcct tgcaggcgtc cgcgctgggt52620gaccgtccgg cggagggtgg tgcgtggctg ccgttctctt ttaccggggt agaactttcc52680ggtcagggtg ggacgatcag cagggcacgg gtggagtcta cgcgacccga tgcggtgtcg52740gtggctgtga tggatgaggg tgggcggttg ctcgcctcga tcgattctct ccggttgcgg52800ccggtgtcgt cggtgcggtt ggcgaatcgg gacgttgtcg gtgacgcgct gttcgaggtg52860acttgggagc cggtggcgac gcggtcgacg gtatcgggtc gctgggcgtt gcttggtgat52920gctgtcggcg gcatggccgg tctcattggg ctcgcaccag gttccgtcga tcgttgtgcg52980ggtctggctg agctcgcggg gaaccttgat tccggtgcgc tggttgctga tgtcgtggtt53040tattgcgccg gtgaacaggc ggatcccgac gccggcgtgg cggcactcgc ggagacccgg53100gagatgctgg ccctggtcca gtcgtggttg gccgaggagc ggttggccgg gtcacgtctg53160
gtggtggtga cgtgtggcgc ggtgacgacg gctgcgggtg acggcgcatc aaagctggcg53220catgcgccgt tgtgggggtt gttgcgttca gcgcagtcgg agaacccggg ccggtttgtg53280ctggtcgatg tggacggtac cgccgagtcg tggcgcgcgt tgccgagtgc ggtggggtcg53340atgcaaccgc agttggccgt gcgtaagggt gtggtgacag tgccgcgtgt ggcgtcggtt53400ccggggccgg tcgaggtgcc cgcggtggtg gccggtcccg accggacggt gctgatttcc53460ggtggcacgg gtctgttggg tggcgtggtg gcacgccacc tggtggccga gcgcggtgtt53520cgtcgagtgg tgttgacggg ccgtcgtggc tgggatgctc ccggaatcac cgagttggtg53580ggtgagctgg agggtttcgg tgcggtggtc gatgtggtgg cgtgcgacgt tgcggatcgt53640gctggtctgg aggggttgct ggcggcggtc ccggcggagt ttccgctgtg tggtgtggtg53700catgccgcgg gtgtgctggc tgacggggtg atcgagtcgt tgacaccgga ggacgtgggg53760gcggtgttcg gtccgaaggc ggcgggggcg tggaacctgc acgagctgac tcgggatatg53820gacttgtcgt ttttcgcgtt gttctcctcg ctgtccgggg tgaccggcgc cgcgggtcag53880ggtaattatg cggcggcgaa cacgttcctg gacgcattgg cgcattaccg gcgggcgcag53940ggattgcctg cggtgtcgtt ggcgtggggc ttgtgggagc agtcgagcgg gatgaccggg54000cggctcagtg atgtcgaccg gagcaggatc gcccgctcca gtccaccgtt gtccaccaag54060gatggtttgc ggctgttcga tgccgggctg gcgttggatc gggcagcggt ggttccggcg54120aggttggaca gggccttcct ggccgagcag gcccggtcgg gaacgctacc cgcgatgctg54180acggcactgg tacctaccat cacctctatc aggcgcagta gtggcaccga cctcgcggac54240gaggacgcct tgcttggggt ggtgcgggag cacgccgcga gggtgctggg gtattcgggt54300gcggccgagg tcggggtcga gcgtgctttc cgggatctgg gctttgattc gttgtctggt54360gtggagttgc gtaatcggct ggccggggtg ctgggagccc ggctgccggc aaccgccgta54420ttcgactacc cgacgccgcg ggcgttggcc cggttcctgc accaggaact ggcaggcgag54480gtcgggacga cgccggcgcc ggtgacgacc acgaccgcga gcgtcgaaga cgatctcgtc54540gcgatagtcg ggatggggtg tcgttatccg ggtggggtgt cctcaccgga ggagctttgg54600cgtttggtgg ccgggggcgt ggatgcggtc gcggacttcc cggacgatcg cggctgggat54660ctggccggat tgttcgatcc agatcccgat cgtttcggga cttcgtatgt gcgtgagggc54720gggttcctgc gggacgcggc ggagttcgat gccgcgtttt tcgggatttc tccgcgtgag54780gcactggcga tggacccgca gcaacggttg ctgctggagc tgtcctggga ggccgttgaa54840cgcgctggga tcgatccggg gtcgctgcgc gggagccgga cgggtgtgtt cgcggggctg54900atgtatcacg actacgccgg acggttcgcg gccggagtgc cggagggctt cgaaggctat54960
ctcggtaatg gcagcgcggg cagtgtggcc tcgggccggg tcgcgtattc gttcggtttc55020gagggtcctg cggtgacggt ggacacggcg tgttcgtcat cgctggtggc gttgcacctg55080gcaggtcaat cactgcgttc cggtgagtgt gatctcgccc ttgccggtgg cgtgacggtg55140atggccaccc cggcgacgtt tgtggagttc tcccgtcagc ggggtctggc accggatggg55200cgctgcaagt cgttcgcgga ggccgcggac gggaccggct ggggcgaggg tgctggccta55260gtgctgttgg agaggttgtc ggatgcccgt cgtaatgggc atcgggtgtt ggcggtggtt55320cgtgggtcgg cggtgaatca ggacggcgcg tcaaacggac tgaccgcgcc gaatggtccc55380tcgcagcaaa gggtgatcac ccaagcactc acgagtgcgg ggttgtccgt gtccgatgtg55440gatgctgtgg aggcgcacgg gaccgggacc aggcttggtg atccgatcga ggcacaggca55500ttgatcgcca cctatggccg tgatcgtgat cctgaccggc cgttgtggtt ggggtcgatg55560aagtccaaca tcggtcacac acaggcagcg gcgggtgttg ccggtgtgat caagatggtg55620atggcgatgc gccacgggga gctgccgcgc acattgcacg tcggcgagcc cacgtcggag55680gtggattggt cggcaggttc ggtccagctc ctcacggaga acacgccctg gcccgacagc55740ggccatcctc gtcgggcggg agtgtcgtcg ttcgggatca gcggcaccaa cgcacacgtc55800atcctcgaac agtctccgac agcgtcaagt gagttcgtgg agcacagcgg acctgattcg55860gaatctgctg tgaatgtccc tgtggttccg tgggtggtgt cgggcaaaac acccgaagcg55920ctcagtgctc aggcggacac cttggtgtcc tatctggacg atcgatctga tgtctcctcg55980cgggatgttg ggtattcgct ggcgatgacg cgttcggcgc tggatgagcg ggcggtggtg56040ctggggtcgg accgtgaaac gttgttgtcc gggttgaaag cactggctgc cggtcatgag56100gccactgggg tggttacggg atctgtgggt tctggcggcc ggcccggttt tgtgttcgcc56160ggtcagggtg gtcagtggtt ggggatgggc cgggggcttt accgggcgtt tccggtgttc56220gctgatgcct ttgacgaagc ttgtgccgga ctggatgcgc atctggggca ggaagtgggg56280gttcgggatg tggtgttcgg ttccgacgcg cagttgctcg atcggacgtt gtgggcgcag56340tcgggtttgt tcgcgttgca ggttggtttg ctgaagttgt tgggttcgtg gggtgttcgg56400cctgttgtag tgctgggcca ttcggtcggg gagctagcag cggcgttcgc cgccggtgtg56460ctgtcgatgg cggaggcggc tcggttggtg gccggtcgtg cccggttgat gcaggcgttg56520ccgtctggcg gtgccatgtt ggcggtggcc gcgaccgagg accgaatcag cccgctgctg56580gatggggtgc gggatcgtgt tggtgtcgca gcggttaatg ctccggggtc ggcggtgctt56640tccggtcacc gggatgtgct tgaggacgtt gttggccggt tggatgggct gggtgttcgg56700tggcgatggt tgcgggtttc gcatgcgttc cattcgtatc ggatggatcc gatgctggat56760
gagttcgccg acatcgcacg gagcgtggat taccggtctc cagggctgcc gattgtctcg56820acgctgaccg gaaacctcga tgacgtgggc gtgatggcta cgccggagta ttgggtgcgt56880caggtgcgag agcccgttcg cttcgccgac ggtgtccagg cgcttgtgaa ccagggcgtc56940gacacgattg tggaactcgg tccggacggg gtgttgtcga gcttggttca tgagtgtgtg57000tcggagtccg ggcgggtgac ggggattccg ttggtgcgga aggaccgtga tgaggtccca57060acggtgctgg ccgctttggc gcagatccac actcgtggtg gcgcggtgga ctgggggtcg57120tttttcgctg gtacgggggc aaagcaggtc gaactgccca cgtatgcctt tcagcgacga57180cggtactggc tggagccatc ggattccggc gatgtgacag gtgctggcct taccggggcg57240gagcatccgc tgttgggggc cgtggtgccg gtcgcgggtg cggatgaggt gctgctgacc57300ggcaggctgt cggtggggac gcatccgtgg ctggccgacc atcgcgtgct gggcgaagtc57360gtcgtccccg gcaccgcgtt gctggagatg gcgtggcggg ccggtagcca ggtcggttgt57420gaacgtgtgg aggagctcac cttggaagca ccgctggttc tgccggagcg gggtgctgcg57480gcggtgcagt tggcggtggg ggctccggac gaggccggcc ggcgcagttt gcagctctat57540tcccgaggcg ctgacgaaga cggcgactgg cggcggattg cctccgggct gttggcccag57600gccagtgtgg tgccgccagc ggattcgact gcatggccgc cggacggtgc tgtgcaggtc57660gatctggcgg agttctacga gcgcctcgcc gagcgcggct tgacttatgg cccggtgttc57720caagggctcc gcgccgcatg gcggtacggc gacgatatct tcgccgagct tgccgtgtca57780ccagacgccg ctggtttcgg catccacccg gcgctgctgg acgctgcact gcacgcgatg57840gcgcttggtg cttcgcccga ctcggaagct cgtctaccgt tttcctggag tggcgcccag57900ttgtaccgcg ctggaggagc agcgcttcgg gtacggctct cgccgctggg caccggtgca57960gtctcattga cgctgatgga tgccgcaggg ggacaagtcg ctgcggtgga atcgctttcg58020acgcgaccgg tctccgccga ccagatcggt gccggtcgcg gcgatcacga gcggctgctg58080cacgtcgagt gggtaaggcc ggctgaatcg gcggggatgt ccctgacctc ctgcgcggtg58140gtcggtttgg acgaaccgga gtggcacgct gccctgaagg ccactggtgt ccaggtcgag58200tcccatgcgg atctggcttc gttggccacc gaggttgcca agcggggatc ggctcctggt58260gcggtgatcg tcccgtgccc gcgaccccag gcgatggagg agctgccgac cgccgcgcga58320agggcgacgc aacaggcgat ggcgttgctg caggaatggc ttgccgatga ccggttcgtc58380agtacgcgcc tgatcctgct gacgcatcgg gcggtcgccg cagttgctgg agaagacgtg58440ttcgacctgg tacacgcgcc gctgtggggc ttggtccgca gcgcgcaggc ggagcacccg58500gaccgattcg ccttgatcga tgtggacgag gcggaagcat cgcgggcagc actcgccgaa58560
gcgctgactg caggagaagc gcagctcgcg gtgcggtcgg gagttgtgct ggtgccccgc58620ctcggccagg tgaaggcgag cggaggtgaa gcgttcaggt gggatgaagg caccgtgttg58680gttaccggcg gaaccggcgg gctaggggcc ctgctcgcac gccatctggt cagcgcacac58740ggtgtgcggc acctgttgct cgcaagtcgt cgcggtctgg cggcgccagg agcggatgag58800ctggtggccg agctggagca gtccggcgcc gatgtcgcgg tcgtcgcgtg cgacgcggca58860gatcgggact cgcttgcgcg gctggtggcg tcggtgcccg cggaaaaccc gttgagggcg58920gtggtgcacg cggccggtgt gctggatgac ggtgtgctga tgtcgatgtc gccggagcgc58980ttggacgcgg tgttgcggtc caaagtggat gccgcgtggt acctgcacga gctgactcgg59040gaactcggtc tgtcggcgtt cgtgttgttc tcctcggtcg cgggcctgct cggtggtgcg59100gggcagagta attacgctgc cggcaacgcg ttcctggatg ccttggcgca ttgccggcag59160gctcaggggc tgcccgcgct gtcgctggcc tccgggctgt gggcgagtat cgatggaatg59220gcgggtgacc tcgctgcggc ggacgtggag cggctgtcgc gggcaggcat tgccccgctt59280tcggcaccgg gagggctggc cctgttcgac gctgccattc gctcggacga accgttgctg59340gcgccggtgc gattggatgt cgaagcactg cgtgtgcagg cccgatccgc ggagacccgg59400attccggaaa tgctgcatgg catggcaatg gggccaagcc gccgcacttc gttcagctcc59460agggttgagc cgttgcaaga acggttggcc ggtttgtcag aggacgaacg tcggcagcaa59520gtgctccagc gcgtccgcgc cgatatcgcg gtggtactgg ggcacggcaa gtcgaacgac59580gtggacaccg agaagccctt ggccgagctg ggtttcgact cgctgacggc catcgaactc59640cgcaaccgcc tcgctaccgc caccggactg cggctacccg caacgctggc cttcgaccac59700ggcaccgcgg cagcactcgc ctggcacgtg tgcgcgcagc tgggtaccgc gaccgtgccg59760gcaccgaggc gaactgacga caacgactcc gcggagcccg tgaggtcgct cttccaacag59820gcgtatgcgg ctggtcggat acttgacggg atggatttgg tgaaggtcgc tgcccagttg59880cgaccggtgt tcggttcgcc tggcgagctg gaatccctgc cgaaacctgt ccagctttcc59940cgtggcccca aagagcctgc cttggtgtgc atgccggcgc tgatcgggat gccgcccgcg60000cagcagtacg cgcggatcgc cgccggcttc cgcgatgtgc gggacgtttc ggtggtcccg60060atgcctggat tcgttgcggg agaaccgctg ccgtccgcca tcgaagtggc ggttcggacg60120caggcggagg cggtgctgca ggagttcgcc ggtgactcgt tcgtgctggt cgggcattcc60180tctgggggct ggctggcgca tgaggtagcc ggtgtgctgg agcgtcgcgg ggtcctcccg60240gccggggtcg tactgctgga cacctacatc ccgggtgaga tcacgccgag gttctccgcg60300gcgatggccc accggacgta tgagaagctc gcgaccttca cggacatgca ggacatcgct60360
atcaccgcga tgggcgggta cttccggatg ttcaccgagt ggaccccaac accgatcggt60420actccgacgc tgttcgtgcg gaccgaagac tgcgtcgcag accctgaagg gcggccgtgg60480accgatgact cctggcggcc ggggtggact ctcgcggatg ccacggtcca ggtgccgggc60540gaccacttct cgatgatgga cgagcactcc gggtccaccg cacaggcagt cgcgagttgg60600cttgagaaac tcagccagcg caccgctcgg caacgttgac gtacaccgtt cagggtgtcg60660gttccgtgtc catgttggct tgcgggagca ggagcaattc tgaagcgagg gatgtagcgt60720aggagcagca tggaacgggc tgtgaacgga agcgttttgc cctgcttttt tcggtttcgc60780aggtcactgt ctcttgtgga cttgactggg ggtcaagggg tcgcaggttc aaatcctgtc60840agcccgacgt tggcggaagc ccgctgaccg gcacgtaagt gcaggtcagc gggcttttta60900tgctgttgtg gatcttgggt gatcgtcccg aagtgtgccg tctcgaattt cggcgatttg60960tgcgaggatt tcgggagttg ttttctggaa gcggaatcgc gaggcggaaa cgctgctgat61020cgtgctgacg ggtggccgat ccgcatccgg aacaaggaga tcgactggtc ggggacaacg61080gcgctgccgg gaggcctcga agactggctc accgaggcgc cgaactatgt ctacctgcgg61140cgggccaagg cgcggccgac cgtcagggac aaggcattcc ggagcaaggt agcggatctc61200gtctccggtg tgaccgggaa ggatcccgag cggattgacg gccagtaccg gcgccagcgg61260cgccagcggg gggcctggcc gcggccgcgg tgcttcggcg ttgctggtgc tcgtcgtcat61320ggcgactgcg ctcattgtcc ggcaacgcga gcagactgac cagcaacggc gcgtcgccgt61380cggccgggag ctgatcaccg cagccgagga cctgcgggac aatgatccga ggctctcgtt61440gctgtccagc ctcgggagac ctgagctcgc cccaccccgg aagcccgtgc cgggctcgtg61500aataccctga tgcggacccg tttcgcaggt accccggcga gtttcaacgc gtacgaactc61560aacctcgtca cggcggccac cggcaaccgg gccgccacca gggcgcggag ccgctcggtc61620gagaccagcc cagatttcat ccacgaggtg gtcctgtggg gacaccggcg gtggtggggc61680gtggcgacgg ctcggggcgc tgcccgagtt cgtcggtgac ggcatctcgc tggcgctgag61740cgcggacggg aacaccctgg ccatcgggga caccgacgaa ggggtggtgc tatgggacat61800caccgacccg ggaaatcccc gcaggctggc cagcgcaccg ggggaggtac gtgtcctcgc61860tcgtgttcgg ccgaaacggg gaggcgcttg ccgtctcggg catcgacggg gtggcgctgt61920gggacatccg cggtgtacgg gaacgggaaa ccttggagcg ccgcgccacc ttgcccgggt61980tggcgcaggc gggcggggtg ctcctcagcc cagatggcct gcagctcgcc accacccggg62040acacgcgccg cgagaccgct ccggacgtta acgaccacca gacgaccctg tgggatgtct62100ccgatctcac gcggcctacc cggccagcgc cgatcagggg gcacttctcc gcgaccctgt62160
tcgacgcggc gttcagcccg gacgggcaca cgatcgccac cgccggcgta cacggcgaca62220tcgtgctggt cgacattacc gacccggcca atcccaagga gctaaccgtc ctctagggac62280actccggcaa gtggatgacc tcggtggcgt tcagcccgga cgggggaaag ttggtcacca62340gcggcgaaga cgacaccgct gtcctgtggt acctcggcga ccggcagcac ccacagcagc62400tggcgacgct ggacggccac gccggcaggg tgtccgcagc ggcgttcagc tcgaacgggg62460cggcggtctt caccgcggat tcctccgcaa ccggcggtcc cgcggcgcgg tgcgccaatg62520gcgggcggcc gaccgtgcgc ggccggtggc gaccggcctc ctgaacggcc acgaactgag62580actgaccgcg gtgtcgacgg ttgacgactc cgcgctcgcc atcgcgagta agccccggtc62640tcctatccct gacccacggt gcaaagtagc caccacgtct tctgcctcat ccccgttgcc62700cgggctcgga ccggtcgtta ggtcgaattt cggcccgacc cggctcgggt tcgtgctgat62760gctgaagttc ttcgagttgg agggccggtt tcctcagttc gtggaggagt tcccgcaggc62820tgcggtcgac tacgtggccg gcgtggtcaa ggtgcccgcg gaggacttgg cgaaatacgg62880yctgtcgtcc cgctcggcga aggggcaccg tacacagatc cgcgagaccc tcgggtacyg62940gcccgcgacc cgcgccgacg aggaacggct gaccgcctgg ctcgccgatg aggtctgccc63000ggtcgagatg gtggaggacc ggctgcgcga ggccctgctt gtgcagtgtc gcagcgacca63060tgtcgagccc ccgggccgcg tcgagcggat cgtggccgca gcacgggcgc gggcggaccg63120cgtcttctgc gcgcagaccg tcgcgcgcct gggcgaggcg tgcgctggcc gcctgctgac63180cctggtggcg gagggcaacg aggagggtac ggcgctgctg gcctcgctga agcgggaccc63240gggcgcggtg gggctggact cgctgctggc ggagatcacg aagctgactg ccgtgcggcg63300gttgggtctg ccggaagggc tgttcgcgga ctgctcggag aagctggtgg ccgcgtgggc63360gggcgcgggc gatcaagatg tatccctcgg acttccggga cgctggcaag gatgtgcgga63420ccatgctgct ggcggcgctg tgcgcgtccc ggcaggcgga gatcaccgat gccctggtgg63480agctgctggt cgctctggtt cacataagat caatgctcgt gccgagcggc gggtggagcg63540gcagctgacg gcggagctga agaaggtacg gggcaaggag ggcatcctct tccagctcgc63600tgatgcgtcg gtcgggcagc ctgaggggac cgtgcgcagg gtgctgtttc cggtggtcgg63660ggagaagacg ctgcgcgacc tggtcgcgga ggcgaacgag aaggcgttca aggccagggt63720ccgtaccacg ctccggtcgt cgtacagctc gtactacccg gcagatgctg ccgtcactgc63780tgcggacgct cggcttcagg tgcaacaaca ccgcctaccg gccggtgatg gacgcgctcg63840tgctgctgga gaagtacgcc gacgtcgacg gcaagacccg cttctacgac gtcggcgacg63900tggtgccgat ggacggccta gtccgcaagg actggcgtga ggcggtcgtc gatgacaagg63960
gcaggaccga gcgcatcccc tatgagctgt gcgtgctggt ggccctgcgg gatgcgatcc64020gccgccgcga gatctatgtc gggggcggga cgcggtggcg caacccggag gacgacctgc64080ccggcgactt cgagtcggcc ggcaccgtgc actacgccgc gattcgccag cccgaggacc64140cggggggagt tcgtcgccgg cctgaagcgg cggatgacgc agggcctgga ccggctgtct64200gcggcgctcg cggacggctc ggagggtggg gtgaaggtca ccacccgcaa gggcgagccc64260tggatcaggg tgccgaagct ggagccgctg gacgagccca cctgcctggc ggccctcaag64320gacgaggttg tacggcggtg gggcgtgctc gacctcctgg atgtgctgaa gaacgccgac64380ttcctcaccg gcttcaccga tgagttctcc tcggtcgccg cctatgagcg catcgaccgt64440gccaccctcc agcggcgtct gctgctcgcg ctgttcgcct gggcaccaac atgggcatcc64500gcgcgatcgt ggcgaccggc gagcacggcg agagcgaggc cgcgctgcgg cacgtgcgtc64560ggcacttcat caccgtcgac aacctgcgcg ccgcggtgac gaagctggtg aacgccacct64620tcgccgctcg ggacgcggca tggtgggggc agggcaccgc gtgcgcgtcg gattcgaaga64680agttcgggtc ctggtcctcg aacttcatga ccgagtacca cgcccgctac ggcgcaacgg64740cgtgatgttt tactggcacg tcgagaagaa gaacgtctgc atctattccc agctcaagag64800ctgttcctcg tccgcaggca tcccgcaggc agggttctcg acgagatcct caaccgcgcc64860accgcctggg ccacccgcgc cgcgtgcggc gaggataccg gcgttccgct ggtcgtgctc64920cacaaccagg tcaaggacag gactgaccga cgataacgat actgtggaca cgagcgcggc64980tcctgacacg atccttcggc gtaaccacct gaaagatcaa cagatagctg cgctcacccc65040ttcaccgggg ccaccaagac taaaccggac aaaccggagc ttccgcccaa aagatcaaac65100cgccggggtc ctgcggcatg accaagttcc tttctgagac aaaggacagt gtccattcgt65160gcagagggct tgtttgatct ctgggcggaa ccaagtatag gaattagcta gacgacgaac65220cgattttact gcgggaatgg gatcccgcgt tctgcgcgcg gctcgcgggc gcatattcgg65280aaacgctgca gcggagaatc gagagcgtcc agatttgcgt acaagattcg ccgtaattgt65340ctaagagtgc tggaagcaac agtttccaaa caaaaggtgc acacaacgtg aatacaccca65400tgacggctgg aagcgtgaac gtggatcccc agcttatgat gcggcatgaa cctgcgaccg65460aggagagcgc ccggatcttc cagcggcgtc gacacgccct tgttggcaca gctcttttca65520acagctactt caaacaagca cgactggacg agctcctgcg gtggacggtg accgagttcg65580agtcgctgca tgtgttcctc cctgacacga ccaccgcttt cacgatgcag gcccgcggct65640atccggcggt ggaagcagag cggaagacgc gacgcgaggc acgaaggctg cgcgggaaga65700tactcgggtc gcttgccatg ctcggcgtcg cgtcccccga gcagatgatc atcgacttcg65760
cctggctcaa cgagaacgag gagtacctgc gcacgaggga cgaggttgcg gaggtcttcg65820ggtcggatga agacttcagg aaggcctgtc tggccgagtc tgaatcggtc gcgaggagca65880ggcggagaac cgacggcagt ctcacggagg aagagctgaa catggcggca cggtacttgc65940tggccgagat cccgcttttc gtaaacgctc ccgccatact tggcatgccc gagactgtgt66000tctgctacca ccgcatcgaa ccgttcgaac gtgacctgta ccgcggcgcg ttcgcggtga66060aagcagtacc tcggcaaggc tgggtcgtgg tcgagtccgc ttcttcggaa atggtggacg66120ccggtgccgc ggccgggtcc ctgccgcgac cacgtaccgc aggtgtgctg tgaaccgcgc66180cgatacggcc gattgcgaac cccggcggtc cggcgagcaa gtacgccgga agtccagcct66240gtggtaggcg cggcttcggc tggtctgcac ggcgaccaaa ccggctggtc ctcctggaat66300ctcgatcgtc ccgccgaccg gcagcgggac gatcgagggg agcagcaaga cccgtagtgc66360ttcaagaagg gttcgctggc tgtgagctgg ggtttcgtcg ggccgtcagg ctgcttggcg66420gtactcgttg atgagtcctg ccacggcttg tcggcgttcg atccgagctg tcggcagcgg66480tatgacgcgc gcgccacgta gggtgcctgc tggtcgtgtg cttggtgggg ccgatgggtg66540ttgaagtggc aggcgtattc ctggcggatc ttctccgcgt ggcctctgtc gaagatcagc66600actcggttgg tgcactcctc gcgaacggag cgtatgaatc gttgcgcgtg cgggttgcgg66660ttggggctgc gcggcgggat cttcgtgacg gtgatgcctt cgctggcgaa gattgtgtcg66720aaggcggcgg tgaacttcgc gtcgcggtca cggatgaggt gcgtaaatgt ggcggcatgt66780caccgagctg ccacagcagc tgccgggcgt gttgagtggc ccaggcggcg gtggggtggg66840cggtgaccct gcggatattc caggccgccg agtgagtgac gacgcgcttg atcgccgttc66900ttgtccagca cctgactccg tcctgagcct cactcggcga atgctcgcga tccattgagc66960gcgagggttt ggcggagtcg gtcggggttc atgagcccgg cggtgggtcg cccttcgcgt67020ttcgtatcca ggagagtggc ttccacgtcg tcgagggccc gccacgaagc tacggcggct67080gctcgaacac gccgacctca ccgatgcgca gcaacgcgcc catcctcggt gctggcgagg67140cgtggccatc gtgccgctca gagtgttaag ccgccgacat cgctgtcgtt tcggatgact67200ttgatgaacc cagtcagggc cccgttggca tcgcgctgcg ctgtgaccac cacgtgcgcc67260cagtaccggg tgccgttctt acgtacccgc cagccctcat cgacagaaaa gcccgcctcg67320gctgcctgat ccagctcctt ctgcggatac ccggctgcga cacgatccgg cgggtagaag67380accgaaacgt gccgaccgat gatctctctg gccgtgtagc ccttcatgcg ttcggcgtcg67440gtgttccagc tcctgacaac gccgtccgca tccagggcga agatcgcata ccggcggttt67500gctgacgtgg cagtcccctc aatgtcaaga cccactgcac aggcccgccc gtcgccggat67560
acgaaggtcg cgataaaccc gaaagtcccg gcggcgtgcg ggacgctcca tgttgagact67620gcacccggga acgcgaccgc ttcaccgggc tttcgtcctg atgtcgcttg tccgtaagcc67680gtcccccacg tcaatcccag cgcctcgcct ttggccgatg ctcaagccga cccgaccacg67740caccgaacac gattacctcg ctctgactcg cccacgcggt gacataatgg acatcaggtg67800attggcggta acgccatgca aagtcgagac acctccgacc agaagcagcc ttggggtagc67860cccgggacgc gcgatagctt caccaatctt gacgcggcac ttcagggcca tccagcgatc67920gagcaggcca agggcatgtt gaagctggcc tacgggatcg atgaccacga cgcactcgaa67980ctgctcgcaa gcatgtcgca cgacacccgt acggacatgc gtgaggtggc ccagacgctg68040gtggagcggg tcacgggcgt agcgaacgcg ccgaccgtga agaccgtgag cgcccgtgtc68100cttgaggagt gggagcgact caaagagcgc taacccagcc ttgcaaaggc gatcaagggg68160catcgtctac ctcggccgct gatcgaacta cgttggtcga cgtgccgcgt ggtttcggtc68220aattgccgtt gttcttcgtt ggtgttggtc ctcgtgcgct ccggatgtgc tccatgcgcg68280tccggggcgt ctgcacagct tcgacctggc cgaaatccat acgatctggt ttcg5acctg68340gcctcccatt caggctccag cgcgttacgg acccgcgcct ggtggcatcg atccatcatc68400gcgagcacag tcgacgatcg tcactggctt cgccaggcgc agctgctcga acaccttctt68460gacgccgcat tccttcgcca caacatctcg caccgtgcca agcagtgccg actgcacggc68520gggaagaatg gcgacactcg cgttcagtgc tggacagtcc ccggccccaa cggcgccgag68580atcctcgacg ccctggggcc ggccgcgacg gtcctccttg atcaccgcac tcgcctgatc68640accgactacc cgtgaaccat catcaccgtc agaccgttgt gggagacggt cgaggatttc68700gcggaggagc tggcggaggc ggcttgagcc caagtccccc tgctcaccct cttcggcgtc68760acccgccggg agcgatcatg accacctggt ggtctccggg ccgtccggtg agggcgtcca68820tcatcgctga gaccggcccg gcgtccaggg ggacgacgtc ggtgatgatc cgctcgaccg68880ggatacggcc gcctccgaga agctccaagg ccgcctcgaa ggcgcctctg ttctgggcga68940agctgcccac gatccggatc tccttggtga tgagggcgac cgagtccagt tctgagggtc69000gctcgttcac tccgagtgcg acgatcgttc cccgtgtccg cacgcgtcgg gccgcgtccg69060tgagcgcggt caccgagccc acgcactcga acaccacgtc tgcgtccggg ccccgctcat69120cgacgtccac ggtggtgatc ccggtcgcgg tcagacgtgc gcgccgtacg gggtgcggtt69180ccaccacccg cacgtcctcg actccccgta gccgcagcac gtgtgccagc aggaagccga69240ccgtgccgcc tccgaggacc gtgacagtat ccgctgccga aattccggag cggtcgaccg69300cgtggaccgc gcaggacagc ggttccgtca gcgccgcgtg ctccagcgaa acaccgtccg69360
gcaccgcgta caccgtgtgc tcggggacga cgacggcttc ggcgtagccg ccggggcgtg69420tgcccaggcc gagggaactc agccgccagg gctgtacagc gcacaggtgg ttgtcgccta69480cccggcagtc gtcgcagtcc ccgcagcccg ctttcggcca caccaccacg gcctgcccag69540ccgtcagccg ctccccgccc ggtgcggcga cgtgcccgga gatttcgtgt ccgagaaccg69600cgtcggccgg gacgaggtgc ggcattgccc gcaggtgcag gtcggaaccg cagatggcgc69660agaacgctac gtccacgcgt acccagccgg gctccggctc gcgttcctcg gcctccgcga69720gccgcagccc gcgctcctcg gtgatgacca gtgccctcaa ttttcctcca cagttttctc69780agcggccagg aacgcccgga tccgggcgac caggatgtcc ggctgctcct cggccgggaa69840atgcccgcag gaggcgatct gcgccccctc aagccgggcg gcgtagtccc gccacaggtc69900gagtacgggc agtgtcccca ccagcccttc ggcgccccac gccacgtgca cgggcattgt69960caggcggcgg cccgcagccg cgtcggcctc gtcagcttcc agatcctcat ggcgagcggc70020gcggtagtcg tcgaagctcg cgcgaagcgc cccgggctgt gcgtacgctt ccgcgtagtg70080ccgcaggtcc gcctcagtga acgcctcgcg ccggaatgct ccggcggcca gcatgaaccg70140gacgtactcc ccggcttttc cttcggtgag gaactcgggg aggtcgggga cgaggtggaa70200gagccagtgc cagtacgcgg ccccgacccg tgcgtccatg tgccgccaca tttcccgcgt70260cggtacgacg ctgagcagta tcaggcggct gatctcgtgt ggccggtcca gtccccaccg70320gtgggccacg cgtgcgcccc ggtcgtgccc gaccacaaca gcctgcgtgt atcccagctc70380gtgcatgagt ccgctcatgt ccgcggccat ggtccgcttg tcgtagccgc cccggggccg70440gctggacgcc ccgtatccgc gcagatccgg cgcgaccacc gtatggtccc gcgcgaggac70500gggcagaacg cggcgccagg cgtagctggt ctgcggccat ccgtggagga acaggatcag70560cggaccctct ccagcgcgcc gtacatggaa ccgcagaccg cccaccgtcc gcgtttcttc70620ccgcgcatgc atcgccacgg cggtttacct cccctgcgct gggaggggaa ttcctacggc70680cccctgcgct gggaggggaa ttcctacggc ccgctgcgct gggaggggaa tttctacggc70740ccgcgctggg gacgtgaatt ccgtcaggta gccgtcgtcg accatggggg cggtgacgag70800ttcgggcagg ggcgcgagca actcggccag gaggccgatc ttttccctgt cggccgacac70860aggccggtgc ggttcctgca gccggtgtgc ggcgaaatcg gctaccaggt cgtccatgat70920ctgctgcggc acctgcgggt cggcgtcgtg ctcgctcagg atgaggtcga gcatgcgggc70980gtgaacgagc gtgacggcct cggcatgggt gaacgatccg cccggacggc tgcgccacgc71040ctcggtcagt tccttctcga cccgctcggg cagtgtccca ggcgggcgtg aggcgaaccg71100gtctgaacgc agagcagtgc gcgccacttg gtaggccatc acggagttgt cgcccgcgaa71160
ggtcacattg acctcgaagt cggtccgcag ggtgacgatc tggttgtggc agtggaaccc71220ctgcgacccg cacatctcgc ggcacgcggc caggacgtcc aggaccagcc aggagccgca71280ttttccggtc gcggtgagca ggtgcatgtt tttacggccg gggtcggtgt gccagtcgcg71340ttcgacgccc ctgacgacgg cgcgttccag caggcgcagc gcgaggcagc gcagttgaac71400cggatacagg cggtccagga acagcggctc gtccaggagg accctgcggg taggcgtggg71460gcgggtttcg cggtgaccgg cgaaccgcca ggtgaggtga gctgcgagtt cggaggctcg71520tgctccggcg ctgagcggga agatacgttc ctggacgaag gtctcgatgg atttcacgaa71580gcgggcgccg gcatcgggaa gcgtgctgga aaaacgtccg cccgcgtcga tgcgcgagta71640ccgccccatc agcgcctcgc gggggagccg gaccccggtg aagcgggcac cgccgacctg71700gttggcctgg atacctccct tcgggtcaca cgacaggatc gtgatacccg gcaggggagg71760accgttctcc tcgccgcgca gcgggacacg gaaccagtgg tggccgacgt cttcgccgtc71820gatcacaagg cgggccagga ccatgccgac ggtcgcggcg tgtttgatgt ttccgatcca71880gaacttgcag gcggcgtccg tgggggtgtc gagcgtgaaa ctctgctcct cacgattcca71940ggagaccgtc gtgcggatct cccgcaggtt ggtaccgccg ccgatctccg tgcagcagaa72000cgcgtagacc tggtgcatcc gcgtgatttc gtcgtggtac cgggcgacct gctcaggggt72060gccgtggttg aacagcgcgc tccccgcgat gaggtgatcg gtgatggtcg aggtgagcgc72120gaaatcgaag gcgcccgtca ggcccatcat ctcgcacatg gaccggaacg cgtgctcccg72180ggactggccc atccacatgt cgttgtcgac gagcccctcc cggaagatcg ctttcatccg72240gtcgatggtc aggtccatgt actcccgcgg ggacagatcg tcacgcagtc gcggatcgaa72300caactcctgc cgcagcaggt cacgcatcgt ccgccggtag gcggaggcgt cctgttccac72360gtccagggca gtcaaccgct ccgcctccgt ggcatgggct tgggtaacga gatgttgccc72420ataagggact gcagttgcgg ccatgtgatc gaaatcctct cgattcgtgg gcatcgcgca72480ttttcaaagg ggaccgtgcc agctgggcag ggcccatcca gcggccgttc acccacggtg72540cgggaaaggc atacaggccg gaagggcaga tattgtcgac tacgagtatc ggggtgccct72600ccgggagaat tccctgcacc gcccgctcgg cctgtttgta cggaaggaac ttctcgtgcg72660gcgaggccac gcacgggtcc gcctccggtc gcagttgccg gatctcgctc cgcgcttcag72720cgcggccagc gggcagacgg tccaccatgc cgtcgaggac catgtcggcg gcgagggccg72780cgtccagttc gtgattggct tcggtagatg cagcgaggaa gagcgcggac cgggaatgcg72840gtgccggctc cgtcgtcgta ctgaggcatt gcatgagaca acgacgcagc cagaacacct72900gaagatcgcc gcgttcaatt gaggtttgcc cattaatcgg gccggtcgcc gaagtggcgg72960
gcacttcccc gcggtaggcg gcgcagaccg catcgatctc ttcggcgagt tccgcggcga73020tacactgtcc tcgcgaatag tgcgcgaagg gatccgtaaa ataggcccct gcgccgggaa73080ccatcagggc ggtgttcatg atcgcctttc atgcgccgca tccaaccaga tatagcgttt73140gtgtctaagg tttctcgccg tccatgctgc gctggttcgc gatctcatgt cgatatgaag73200gcaagcaggt atcgcagtgg gtgtcgcagg tcattgcgcc tggtgtccgt gatggcattt73260gccggtattg ataatgactt ctcgagtatc cctcaagctc atacgatcgg cggatggttt73320gcccgtctac ccatctcgtg ttgcccgtct gttccctggt tcgatgagta ccggcgctgc73380tgctcgaccc ggccaagcgg gacgccggtc gtggactgtg aactcagcga gatcgaagat73440gtgctgcgcg aacaccaccg ggttgatgat gctctggtcc tgcagggtgc gaagatcgaa73500gcgcacctcg tggtgaccga accagtgcag ccagccaact ctgtcgacct ggtgcaccct73560cctcctcggc acgtgcgaac cgtatgttta cgaggcggat ccgcagttga cgcgcgatga73620gagcgatgct ttggtgaatc acctattcgc ggtttccgag agtccgcagc gcgtttgaag73680gtaccggtgg gttccgggcg cggtcgaggt gtgggacaat cgggcgactc aacgcaataa73740cacactggcc gcaccacgca gcagttgtct accgggctgg ccattgctgt tgccacggtg73800gcactgcggc tcggtgaacc gttgggtgag ctggtgttcg gtgcgcgtag cggggctacc73860tacaccgtag ccttcatcct gcttgggctg actgcgctga tcgccactgc cggggcgttg73920agcctgcacc cgaatgccgg caacgccgtg cgcacgctgg gcacgcgggc gagcgggcga73980gcgcgacctc caccacggaa ccgggctgag actgccagca gttggacgtt gcaggccagc74040atgcaacgtc atgacaccaa cgacataagc aggtcacagc tgcagaggcg atcctctcgt74100tagcaacgag agattcgggc aacccccgag ggcactttcg ggtagaccga gagattcgat74160cttcttatcc ttgactcccg ccgcatagct ttccactgcg accgccccga cggtgcggga74220aatcatgtcg atcaacatca acggcggaat ccacagtgga cgttgtttct gccgcgtctc74280ggatgccacg ccgcgggtgg gaacgtgcag gtacgtgccg gagaagagga gaacgaccgt74340ggctgaggta gtggaatcac cctcacccaa ctcgttggaa gacgtacgcc cgctaccgca74400tcctcgatcc acgcgccagg gtcaagtcga acaactcccc gagttgactc cggcgttgtt74460gctggagtta actacggggc tctggagttt caaggcttcg ccgccgctgt cgagctggag74520ctgttcacca agctctccga cctcggctcg gccacagtcg aaacagcgtc cgaggccctc74580ggaccgcccg atcggcccac cgatctgcta ctggccgcgt gtgcgtctcc caactgaggc74640cctgcgggct ggtcgtacat aagaaggggc tcccgcagcc cagggagtga ctgtaactcc74700cgcagggggg ccgccacccg caccgccacg caaaacgagt tccgctaaca ggatctaagc74760
gttgtgtcca gccgagagcg aaggaagaga catgccggca atccgattgg cagcgctggg74820tgacagcttc gtcgagggcc gtggtgatcc tttaaaacct cagcaatccc aggaggccga74880cctgaaccgc gaagatcccc ggctgcgccc acaacgtccg gtcgagcacc tgctcatcag74940caccgaacag cacgccccgg acgtccacgc ccaagtccgc gcccaagtgc gcgcccaagt75000gcgcgcccag cgcgtcgcag gcttcctcga aggcgtctgc gaacgccggg aaagccgcgc75060acaacgcctt tcccatcccc agccactgac tgccctgacc ggaaaaaacg aatccgatgc75120ggccaccgga attcgcagcg ccggtgacca cccccggcgc agtccggcca tcggccagcg75180ctgccagcct cgacaacagg gtctgatgaa ctacttgcag ttgacctcga atctct75236<210>2<211>36538<212>DNA<213>Saccharopolyspora sp.NRRL30141<400>2tcggtactgc ccctccgatt cctggacaca ccatcagcaa gttcggcgtc ttccggcgcc60tccaccggcg attccggagc gcctgcatat catcgagttg cggcacacct tcagccgacc120ggcttccgcg ccgtcaaaat cgcatagccc atgtcgtcgg cgtatttctc gtaatcgcag180accgcggcgg cccagtcggc gacagccggc ccgtaccttt ccgcgatccc gtgctggtgc240gcagcgagcg cttcggcgaa ctgcggcatg aagtaccggg tccgcgacga cacgtcgtca300caagcgagga tttcgaaacc cgctgcacac agcgattcca gaagttgctc agccaggcag360atccggaggc cggtcggcca catgtcccag gacaccggga tcccgctgcc tatttctcgt420ttgacgacct cggtgactcc gaggatgcca ccgggtttga gcactcgaac gatttcccgg480atggcacggt ccggttccga catctccaac agcgactgga tggcccaggc agcgtcgaac540gcattgtccg ggtacggcag ggacatggcg tcgacgcacg agaagtccac ctggtggctt600agtccgcgtt cgcgggcgca atcaacggcg atggcagctt gcacctggct gaccgtgatg660ccggtgatcc ggatcgcgtt gtcgcgcgcg acgcgcagcg ctggttgtcc ggtgccgcac720cccacatcca gcagtcgatt gccgccatcg agcgcggtcc gttcggcgac aagatcggtg780agccggtcgg cggcctgctg ccaggaagtc cgcccgtcgt tctcccagta gccgtggtgg840atggcgcagg ggccgcccgc gaccgaattc agcaacgggg tgaccaggtc atacatctgc900ccgacctgct gcgatgttgg cacgccacct ggcaacaccg gtatgcctga tccctgcaac960gttcaccttc tcgaaatttt cttcaccgag cagacacaca gagagaaaag aaggcaaact1020agccgtcagt taattcgcgg ttaccgccgc atgcggcggt aacaactaat aaccatccgg1080
ccaggaggcg aacagccagc gcaaattttc cccatgaatc cccgcagagc caacggtgat1140cagcgtatag gtctgtccca ccctgatcga gcgaagctca agcatttcac tcagacgggt1200gaaaccaggt gcggcaagct aaagatcctc gatgggggcg tgacactcct gcggcgacac1260actattattg ccgccggaag tccgttggac gtcaacggcc atcgacatac gcagcgcatt1320ttcctactcc tgaccaacag gagtaggggt tgctgcgcca atcgggggaa gagaccgggg1380tccgaagtat gcgcgtactc gtcgttccct tgccctatcc gacgcatctc atggcaatgg1440tgccgctgtg ctgggcgctg cgagcatccg ggcacgaggt tctggtcgcc gcgccaccgg1500agctgcaggc gaccgcgcat ggcgccggtc tcaccacggc cgagatccgc gggaacgaca1560agacccgcga cacgggtagc accacgcggc tgcgctttcc caatccggcg ttcggtcagc1620gcgacaccga gaccggccgg caactgtggg aacagaccgc gtcctatgtc gtgcagagct1680cgctcgatca gctccccgaa taccttcgac tggccgaggc ctggcgaccg tcagtgctgt1740tggtcgacgt ctgcgcgctg atcggccggg tgctcggcgg attgctcgac ctgccggtcg1800tgctgcaccg ctggggagtc gaccccaccg caggcccctt cagcgatcga gcccacgagt1860tgctcgaccc ggtgtgccgc caccacggac tggccggact gccgactcca gagctcatac1920tcgatccctg cccgcctagc ctgcaagcaa gcgacgcgcc gcgaggcgtt ccggtccagt1980acgtgccgta caacgggagc ggcgaactcc cggcctgggg cgcggcgcgc acctcagcac2040ggcgggtctg catctgcatg ggccgcatgg tgctgaacgc caccggaccg gctccgctgc2100tgcgcgcggt agcggctgcc accgggctgc ccggcgtcga ggctgtgatc gccgttcccc2160ctgagcaccg ggcacttctc accgacctac cggacaacgc acggatcgcc gaatcggtcc2220cgctcaacct gttcctgcgt acctgcgagc tggtcatctg cgcgggcggc tcgggaacgg2280cgttcaccgc gacccgactc ggcatcccgc aactcgtgct tccccagtac ttcgaccagt2340tcgactacgc gcgcaacctc accgctgccg gggcgggcat ctgcttgccg gatgagcagg2400cccagtccga ccacgaacag ttcaccggct ccatcgcaac agtgctcggc gacaccggct2460tcgcggctgc cgcaaccaaa ctcagcgacg agatcacggc catgcccaat cccgccgagc2520tggtgcggac gctggagagc tccgcggcca tcggtgcctg acgaactgct cacccgagaa2580cagacggatc cggagaaccg atgccctccc agaacgcgtt gtacctggac ctgctcaaga2640aggtactcac caacacgatc tacggtgatc ggccgcatac gaacgtctgg caggacaaca2700ccgactacag gcaggccgct cgggccaaag gcacggactg gccgactgtc gcgcacacga2760tgatcggtct ggagcggctg gacaacctcc agcactgcgt ggaagccgtg ctcgcagacg2820gtgttcccgg ggatttcgcc gagaccggtg tctggcgggg cggcgcatgc atcttcatgc2880
gcgcggttct ccaggcattc ggagataccg gacgtaccgt ctgggtggtg gattctttcc2940agggaatgcc ggaaagctct gcgcaagacc acgagtcgga ccaggctatg gcgctgcacg3000agtacaacga cgtgcttggc gtcccgcttg agaccgtccg gcagaacttc gcccgctacg3060ggctgctcga cgaacaggtc aggttcctcc ctggctggtt ccgggacacc ttgcccaccg3120cccccatcca ggaactcgct gtgctgcgac tcgacggcga cctctacgaa tccacaatgg3180actctttgcg gaacctgtac ccgaagctct cgccgggcgg attcgtcatc atcgacgact3240acgtcctgcc gtcctgccag gacgcggtga aggggttccg cgcggaactc gggatcacgg3300aacccatcca cgacatcgac ggcacgggcg cctactggcg ccgcagctgg tgaacggctc3360agctgtcctc gacgccgagc gcttgccggg gcacgaaccc cggcgcggca ggctcagcgt3420tgagcccttt ttccacgaat accaggttgt ggtagaagtg cagggccgcc acgttccgtt3480ccgtgtagca gggctcggtc ccgcgccgcg attcgcgctc ctgataatgc aggccgtcga3540tcagttcttt gagcatgtcg atcgaggtgc gctgggccgc gggttccgta tcgcggccgc3600cgtagccggg ccagtacgac gtctggagat cttcgatgac gtacaaacca cccgggcgga3660cgtgcggaaa cagggcatgg aaggacttct tgacgtggtc gttgacatgg ctgccgtcgt3720cgatgacgat gtcgaacggg ccgatcttcc ccgccatgtc tgccaggaat tccgcatcgc3780tctggtcacc tcgcagcttt cgcactcggt gtccttcgtt cccggctttc tcgaaaatgt3840ccaggccgta cacgagacct cgccggaagt accgctgcca catgcgcagc gaagcgccac3900cgagttcggg tgcgtggtaa ccaccgattc ctatttccag cacgcgcacc gggacatcct3960ggaatcggga gaagtggtgc tcgtagtgtt cggtgtacca gtgcaggtcc gcccatttgt4020cggatccgta gcggaccgcc agctcaccga ggtccgagca cctggtggcg gctgcggcca4080gcaccgcgtg caccgcggtg gacaccttgt tccggaacgc cagcagtcgc tgcgcgccgg4140ccaggccctg gtcgggggag aactgcgtca tgctgtccga ccaacggact tcacggctgt4200tgtgccgcct gccgtcaacc gggccgaaga gcccttcgag cagatccacc gcgtcgaacc4260ggagaacagc aggtgcttcg gcgaccgccg cgagccgcag gcctgcgtga tcgagctcaa4320cggttctacg gaccagctga gcgccagaag tgatctccag gccgattcgc accgactcgt4380ccaacgacag cggatcgcaa cgcacgacga gttcgtcgac gatggcgtcg gccaccgcct4440ccagtccagc cacctgcact gcttcctgga gcctctccgt gcccgcaccc gccgcgagca4500gcaagtgctc caccaccgac cagggggcaa ctgcgatctc acccatggaa agtcatcacc4560ttttcggttc ctgcgcatag gacgccatgc gcaccgcgat accgatccac aaagtagagc4620cggcggaggc gaccagcttt cacgtatgag ccgaaacaca cagataatca cccggacgcg4680
tggatgatct cggccgaggg cgaacaaagt ggaccagtca gcaaaggagg ggcggtgccc4740gatttccatg acccagcaac catgaatcgc cgaaccccag gaacagagat caccgtcgag4800cccggcgatc ctcgttatcc ggacctcgtc gtcgggcaca acccccgttt caccggaaaa4860cccgaacgca tccacatcgc cggctccacc gaagacgtcg tgcacgctgt cgccgaagcc4920gtgcgcaccg gcaggcgggt cggggtgcgc agcggcgggc actgcttcga gaatctcgtt4980gcggacccgg cgatccgggt gctcgtcgac ctctccgagc tcaaccgcgt gtacttcgac5040agcacgcgcg gggcattcgc gatcgaggcg ggcgccgcgc tcgggcaggt ataccgaacc5100ctgttcaaga actggggcgt gacgatcccg accggcgcat gtcccggggt gggcgcaggc5160gggcacatcc ccggcggggg atacggcccg ctgtcgcgcc gattcggttc ggtcgtcgac5220taccttcaag gcgtcgaggt cgtcgtggtc gaccgggccg gtgaagtgca cattgtcgag5280gtcgaccgga attccattgg tgccggtcac gacttgtggt gggcgcacac cggtggtggt5340ggcggcaact tcggggtcgt caccaggttc tggctccgag cgccggacgt ggtcagcacc5400gacccctcgg agctcctgcc acggccgccc gcgacggtgc tgctccgatc gttccactgg5460ccgtggtgcg aactgacaga gcagtcattc gccctcctgc tacggaactt cggcacttgg5520tacgagcagc acagcgcgcc ggaatccacg caactcgggt tgttcagcac gctcgtctgc5580gcacaccgcc aagccggcta cgtcacgctg aacatccatc tggacggcac ggatccgaac5640gcggaacgca ccttggccga acacctatcg gcgatcaacg accaggtcgg cgtgactcca5700gccgaagggc tgcgggaaac cctgccgtgg ttgcgatcga cccaggtgtc cggatcgctc5760gccgaaggcg gcgagccgag cgggcagcgg accaaggtca aggccgccta cttgcgcacc5820gggctgtccg aagcgcaact agccacggtt taccggcggc tgaccgactc cggatacgac5880aaccccgcag cagcgctgtt gctgctcggt tacggcggta gggcgaatgc cgtggcgccg5940tcggccacag cgctcgctca gcgcgactcg gttctcaaag cgctgttcgt cacgaactgg6000tcggagcccg ccgaggacga gcggcatctg acctggattc gtggtttcta ccgcgagatg6060tacgccgaaa ccggcggagt tccggtgcca ggtacccgtg tcgacggctc ctacatcaac6120tacccggaca ccgacctggc cgatccattg tggaacacct ccggagttgc ctggcacgac6180ctgtactaca aggacaacta cccgcggctg caacgggcca aagcgcggtg ggacccacag6240aacatcttcc agcacggcct gtcgatcaaa ccgccggaac ggctttcacc cggtcagcca6300tgaggagtcc gtcacgatgt ccgcaacgca cgagatcgaa accgtggaac gcatcatcct6360cgccgccgga tccagtgcgg cgagtctggc cgaactgacc accgaactcg gactggccag6420gatcgcaccc gtgctgatcg aggagatcct cttccgcgcg gaaccggccc ccgacatcga6480
accgaccgag gtcgcggtcc agatcaccca cggggtcgag accgttgact tcgtcctgaa6540gctacagtcc ggtgagctca tcaaggccga gcaacgaccg gtcggagacg tcccgctgcg6600gatcggttac gagctcaccg atctcatcgc cgagttgttc ggcccaggag ctccgagggc6660cgtcggtgcc aggagcacca acttcctccg aaccaccaca tccggttcga tacccggccc6720gtccgaactg tccgatggct tccaagccat ctccgcagtg gtcgccggct gcgggcaccg6780acgtcccgac ctcgaccagc tcgcctccca ctaccgcacg gacaagtggg gcggtctgca6840ctggttcacc ccgctgtacg agcgacatct cggcgagttt cgtgatcgcc cggtgcgcat6900cctggagatc ggtgtcggtg gctacaactt cgacggtggc ggcggcgagt ccctgaaaat6960gtggaagcgc tacttccacc gcggcctcgt gttcgggatg gacgtcttcg acaagtcctt7020cctcgaccag cagcggctat acaccgtccg cgccgaccag agcaagcccg aggagttggc7080cgccgtcgac gacgagtacg gaccgttcga catcatcatc gacgacggca gccacatcaa7140cggacatgtg cgcacgtccc tggaaacgct gtttccccgg ttgcgcagcg gtggcgtata7200cgtgatcgag gatctgtgga cgacctatgc tcccggattc ggcgggcagg cgcagtcccc7260ggccgcgccc ggcaccacgg tcagcctgct caagaacctg ctggaaggcg ttcaacacga7320ggagcagccg catgcgggct cgtacgagcc gagctacctg gaacgcaatg tggtcggcct7380ccacgtctac cacaacatcg cgttcctgga gaaaggcgtc aacgccgagg gcgccgttcc7440tgcttgggtg ccgaggagtc tagacgacat tttgcacctg gccgacgtga acagcgcgga7500ggacaagtga acagcaaagg gtcgaacgca caggcctttc caagcgcgga tcaggtggag7560tccatcttcg acgcgttggc gcaagggcgt gccctgcacc acggatactg ggcgggcggg7620tatcgggagg atgccggggc cacaccttgg tcggacgctg ccgaccacct gaccgacctg7680ttcatcgaca aggccgcgct ccgccccgga gcgcacctgt tcgacctggg ctgtggcaat7740gggcagcccg tagtccgcgc ggcacgcacc aaaggcgttc gagtcaccgg aatcaccgtg7800aacgccgaac atctcgccgc cgctaccagg ctcgccaacg agaccggact ggccgacagt7860cttcggttcg atctagtcga cggcgcccgg ctgccctacc cggaaggttc ctttcacgcc7920gcatgggcga tgcagtccgt ggtacagatc gtcgaccagg ctgccgcgat ccgcgaggtc7980caccgaatcc tggaacccgg cggccagttc gtcctcgggg acatcatcac tcgtgctcga8040ctcccggaag agtacgcggc ggtttggacc ggcacgaccg cccatacctt gaacagcctc8100accgcgctgg taagcgaagc cgggttcgag attctcgaag tcaccgacct cacggcgcag8160accagatgca tggtctcctg gtatgtcgac gagttgctcc gggaactcga tgagctcgcc8220ggcgtcgagc ctgcggctgt cggcacctac cagcaacgct acttgggaga catcgcggcg8280
aagcacggac cgggaccagc gcagctgatc gccgcggtcg cggaataccg gaaacatccg8340gattacgcca gaaacgagga aagcatgggt ttcatgctcc tgcaggcgcg aaagaagcag8400tcctgatggc ctccgagcac gccagcctgg tcggcgacga tctgcgggca cccgcggacg8460atcccttcta ccgaccgccg acgccgctgc cgccgggtgc cccgggcacg ctcatcaggg8520cccggcccgt cacggcactg cgcagcacgg gcgaacccgt cgcggccaag gtctggcaaa8580tcctctaccg gtccaactcc gccattggca ggccgaacgc cgtctccggc accgttctgg8640tgccgaacat cccgtggccg ggcgaagatc gccccatcat cactttcgca gtgggcaccc8700acggcctcgg cagccaagtt gccccgtcct acctgctccg aaccggaacc gagccggaga8760ccgagctgat cgccgtggcg ctcgaccgcg ggtgggccgt ggtcatcacc gactacgagg8820gcctcggtac tccgggaacg cacacctaca ccgtcggcag gccgcaggga cacgccatgc8880tcgatgccgc ccgcgctgcg cagcggctac cgggctcggg cctggggacc gactgcccgg8940tcggcatctg gggctatgcg cagggtgggc aagcgtcggc cttcgccggc gaactgcacc9000ccacctacgc ccctgaattg ccaatccgcg ctgcggccgc aggtgcggtg ccgatcgatc9060tgctggacat cctccaccga aatgacgggg tgttcaccgg gccagtgctg gccggcctgg9120tcgggcatgc cgccgcctac cccgatctgc cattcgacga gctgctcacc gacgcgggtc9180gtatcgccgt tgatcaagtg cgcgagctcg gcgcaccgga gctcgtcacc cgcttcctcg9240gccgcgagct gagcgatttc cttgatactt ccggcctttt cgagcaccct cgatggcgag9300cacgactggt ggagagcgtc gcaggtagga acggcggccc ggtggtcccc acgctcgtct9360accacagtac ggacgacgag atcgttccgt tcgcattcgg cgagcgactc cgggacagct9420accgcgcagc gggtacgccg gtgcggtggc atccgctctc cggattggct cacttccccg9480ctgccctggc cagctcgcga gtggtcgtct cctggttcga cgagcacttc tccgggccgt9540ccgcgatcag cggtccgcga gatgacgggt gagcggatgg cggtgagcct ctccagcggc9600ttcaccgccg gcttccggat gcccggtcag gcttcgaggc gaactactac ccgcggatgc9660cggacggcta cgtggacccg caccggcagg cctgaccgat cgcctccacc agcgcggcct9720gctggatcat cgattcgccc gaatctccgg ccaccgcagg ttcgtccacg cctgcctctg9780ctctgatgtc gcgtgcaaag gcggtgaccg ccttgcgaac ctgatcttcc gctggcaagg9840acaactcgtc gacaacgccc ttccgctcga ttcggatcac ggcctgccac tcggcgggcg9900gagtgaacgc ccgatcgatg acgattcgtc cacgactccc ccacagctcg tacgcgctgc9960ggtagtggtg cacgaaaccg tatccgaggt gggcaacggc gccaccttcc gattggagca10020gcacgctgcc cgacaagtcg acgcccgact catgagcctc gtgcgagctt gcgccggcaa10080
ccgtgagcgg accgaggaga aagagccgag cggcacgggc gggatagaca ccgatgtcca10140gcaacgcccc gccaccgagt tcggtgcgat agcggatgtc cgtgtcggaa agcggcggaa10200tcccgaacac ggcggtgaac tcccggagct caccgatctc ctcggattgc agcaggtcgc10260ggaccacgtc gtgccggccg tggtggagga acaggtaatt ctcccgcagc agcaggtgct10320tccgccgggc cagcccgacc aggcgagcgg tttcggacgc cgtcgtcgtc agcggtttct10380cggcaagcac gtgtttgcct gcctcaagcg ccttgccgat ccactctgca tgcatgccag10440gaggcaacgg cacgtagacg gcatcgatgt ccggccgctc caggagccgc tggtaaccca10500gcaccgcctc gcattcgaat cgtgctgcga accgttcggc cttcgccgga tgacggctcg10560ccaccgccac cacctctgtt tcggccacgt cgcacatcgc gggcagcatc cgtcgccaag10620cgaaggaagc acacccgagc acaccgatgc gcaccggctt tcgcatcgag ctggtcatcg10680ccccaacgcc cacaagctat gcagggaggc aaccaagctg cgcgcctgga tgttcaagga10740gtgggtgctc cggagcagct cgcccaactg gcccaaggtc atccaccgga agtcgctcgg10800aggtcgtgcc gcgaagtcct catgcacctc gatgatccgg tacctgttct gcgcctggta10860gaaccgaccg ccttcttcag acaggatcga ttcgtaccgc acggtttcgg gatcggcggt10920gagcacgtcg tccacgaacg gcggccagtc gttgcgcgga gtgctttggt agttggccac10980actgcactgg accgtgggag cgatttccgc agtcgacttg taaccagcct ctacccgagc11040gcggaccaaa ccgtgcagca ctcctccgat ccgtttgacc aacagtgcga tctcacctgg11100ttctcgcggt tcgatcatcg gctgagtcca gctggagacc tcacgattgg tcgcggacac11160cgacactgcg atcaccgaga agtacttgcc gtcctggtgg gcgatctcgg tgtcggtgcg11220ataccacttg tcgaccctac tgagcggaac gcgcgttgcc cgcaagctgt agcgggcctt11280ggcttcctcg aaccaaccga ccgcctcggt aatactcgcc gaatcgatgc cgtgcgagag11340cgacctggcc accgcctgcc ggaagggctc cgccgaggcg gctagtccgg gcccggtggc11400ggaatcgtgg aacgggatgc aagacagcac cgtccgggtg tccatgttga cgatgttgtc11460ctgacgaagg agatccagca cctggccgag ggtcaaccag cagaagtcgg gcaggactgg11520cacttcctcg tcgacttcca ccaccatgtt acggttacgt ttccggtaga accaggcccc11580ctgttcagac tggagcacgt ctaccagcac gcggctgcgg ccccgcccga gcaagtagtc11640cacatagggt ggaacgctgc cacgatgtgc ctgcgtgtag ttgctccgag ttgcctggac11700cgtcggcgag agctgcagga cgttgacgtt gccgggttcc atcttggctg acatgaggca11760gtgcagcacg ccgtcgatct ccttgacgag aatgccgagg atacctactt cagcctggtt11820gatgatcggt tgatgccagc aggtcgccgc gccatagttg gtctcgacct gcaggccttc11880
taccgtgaaa aatctgccat cagcatgaac caggttctca gtgctggcat cgaatttcca11940tttcgacagg cggtcgaacg ggatgcgagt ggtctcgaag ctgttctcgc ccaaccggtc12000ggccagccag cagtggaaac gcgtggtcgg aaacctgcca ttgcaagcgc tcagcgcaga12060gtcgacgaac cgccgcgtgt tgttgctgct gagcggcgca gcagcacttg cctcagcttc12120ggcaaaactg ctcataccca atccctcact gccgtgacga tgtgcacgcc gactcccagg12180ggcatcgcgg tctggtccag cgacctggcg aggatcaccg aagcgatccg cccgtaatga12240ccgcgagcac ctcgtcctgg cgttcggtca ttgaagaaat gcccgccgga gaagacacgg12300acatcggcct cagcctcggt gtgctctcgc caggcttccg cctcctccag ggtgaccttc12360gggtcggcat ctcccaccag cacatcgaac cgcggcgcga gcgctcggga cagcgggaag12420tagaagctgg ccgaaccacc tgcgtgcgga gcacgaccaa acgtgttcca gccccgggcg12480ccgggtggaa gcgacggatc caaatctcgc tgtgggttgc caagtcggtc acaattctcc12540ctcggacgac ggccgaactg gcgtgaacac ccaccccgcc ctggtagcgc accgactttc12600agagtcatca atcggtgttc tcgacaccag cggagcagga agtgagtggc atggcgatgc12660aagcggtcag gacagccgct gcggacgcgg catgacgtac ctttccaact tgtagtgcgc12720tgttgcttag cgggcgtcac gatcttcgtc ggaaagcggt tggagcgcaa acatctgggg12780agatcaacac tccattgggg gattccggac gagaatctga tttcgggact cgttcggcgt12840ccatgttgcc ggccatacgt tgctcacaga tggccgtcag acttcccagc gcggcggttc12900ttaccttcgg caaccagctt ctccagacgt gcaacgatgt cgtgcgggct gggattttcc12960tcgatttcac cgcggatcag cgccgcgttg gcggcgaacg acggctcgtc gagcaggcgg13020gccagctgac gtcgcacgtc gtcttcggta aacgtcgcgc ggtcgaggac cagaccggct13080ccccggtcgg cgaggagctc tgccctacga gattcgtccc agaaggtccc aggaagaatc13140aactgcggta cgccgttgac cgtggcggtt tcctgcgtcg tcgttgagcc atggtggatg13200atcgctgaac acgactccag cagttcgttg agcggtacgt attcgtggac ccggacgttc13260gggggcaact cccccatctc ccgtacttca ccgccagaca aggtggcgat cacctcgacg13320tcgagcccgg ccgcgccgcg caacaacgtt tccaccattg cctgttcctg ggcttctccc13380tcccactgct cggccaccct gctctgctgc cgcttggtca gcccgcgggt gacgcagaca13440cgcggcttgg tcggtggttc gcgcaaccac tccggcacca ccgccggacc gttgtacggc13500acgaagcgca tcgagatgta gtccaagtcc acaggcagtc gcatccagga tgaaaccgga13560tctatggtcg cttggcccgt cacgatctct tcatcgaacg tggcaccgaa cttggagagc13620ttcgctccga gccacgcccc gagcgggtcg acgcgctgct caggcggctt cgattccagg13680
tattcgagga aaccggaccg cagccacccc gacacatcga gggcgacgag catccgtacg13740tgtcgtacgc cgagcgcttg cgccacaact ggccccgaac acaccatggc gtcccacaca13800acgagatccg gctgccattt ctcggcgaac cccatgagat cgtccagcga tcggtcatcc13860acaaggtgga gttgctccac ggcgtccatg tctctgccag agttgattga cagcagctcg13920tcgaagagtt ccggacgccg gccctcgtcg aacgcgaccc cgttgccgag aacgagtttg13980ttcctggccg ccaaggagat gaggtcgagc tcgtcgccga cgggaaccgc ggtgagtccc14040gctccggtga ccatcgacac catattcggg cagatggcga cacggacctc gtgccccgcc14100gcacgcaacg cccacgccaa cggcaccagg ttgaagaagt gcgaactcgc cggtagcggg14160gtgaacagaa cacgcatgca ctctccgatc gcaattgaac acccgggaaa acatggcaag14220aatcacagaa acatgtgata tacccccggg aaacgccgct cccctaagct acatcttcct14280cggtgcatcc aggcttaggc cttccaggtg atggtagcga tcttgacaag cgcaagcagg14340tcgttcccgc tagcctggac tctgtcgagt cgggtgtgcc gggtagatcg aggagcactg14400agtcaatgag cgcttctctg tgctccgctg tcctcatgtc ccgcaccgtg tcgaaccagg14460acaggaagga gtcatgctcc gggacagcac cattgtccca ctgggacccc ataacgcgat14520tcgccacggg aatcgctcac ctcctgaagg tcaaggcgcg aggactgatc gtcgcctgca14580tgcagagccg gaaaaagccg gagcgttggg gaaagggcgc gccagagtga cttcgtgtga14640cgacacttgc gctaccgcta ctgagatgac gccggatgcc aaggaccgga tattggcatc14700cgtgcgcgat taccaccgcg agcagaaatc ttcgatcttc gtagctggat cgacaccgat14760ccgaccatcg ggcgccgtgc tcgacgagga cgaccgggtg gcgctggtgg aagccgcgct14820ggagcttcgg atcgccgcag gcgggaatgc tcggcgattc gagagcgagt tcgcccgctt14880cttcggcctc cgcaaggctc acctcaccaa ctccggttcg tcggcaaatc ttctggcgtt14940gagttcgctt acctccccca acctcggcga ggcacgacta cggcccggcg acgaagtgat15000cactgcggcg gtcgggttcc ccacgaccat caatccagcg gtccaaaacg gactcgtccc15060ggtattcgtc gacgtggaac tgggcaccta caacgcaacg ccggaccgca tcaaggccgc15120cgtctcggaa cggacgcgag ccatcatgct ggcgcacacc ttgggcaacc cctttgccgc15180tgacgaaatc gcagagatcg cacgagaaca cgagctgttc ctcatcgaag acaactgcga15240tgcggtggga tccacctacc ggggacggct gaccggaacc ttcggcgacc tgacaacggt15300cagcttctat cctgcccatc acatcaccag cggtgagggt ggctgcgtgt tgaccggcag15360tctggagttg gctcgcatca tcgagtcgct gcgtgactgg ggacgggatt gctggtgcga15420gcccggcgtg gacaacacct gccgcaagag gttcgattac cagctcggta ctctcccagc15480
cggctacgac cacaagtaca cgttctccca cgtcggttac aacctcaaga ccaccgacct15540gcaggccgcg cttgcgctga gccagctgag caagatttcc gaattcggat cggcacgccg15600ccgtaactgg cgacggttgc gcgaaggtct gtccggggtg ccgggcctgc tgctgccggt15660gcccacgccg cacagcgacc cgagctggtt cgggtttgcg atcactgtca gtgcagacgc15720cgggttcacc cgtgccgccc tggtgaactt cctggaatcc cgcaacatcg gcacccgact15780gctgttcggc ggtaacatca cccggcaccc ggccttccag catgtgcggt accggattgc15840cgacgcgctc accaacagcg acatcgtcac cgaccgaacc ttctgggtcg gcgtataccc15900aggcataacc gaccaaatga tcgactacgt cgccgaatcg atcgctgaat tcgtggccaa15960gaattcctag catccagcat ggctgcatct cggaggattt cagcaacgtg atcaacctgc16020accagccgac cctcggcgcc gaagaactcg acgcgatcgc ggaggtgttc gccagcaact16080ggatcgggct cgggccgcgc acccggacgt tcgaggccga cttcgcccac cacctgggcg16140tggatcccga ccagatcgtg ttcgtcaact cggggactgc cgcgctgttc cttaccgtgc16200aggtgctcga cctcggccca ggcgacgacg tggtacttcc ttcgataagc ttcgtagcgg16260cggccaacgc catcgcatcc tccggtgccc gcccggtgtt ctgcgacgtc gacccccgga16320cgttgaaccc cactctggat gatgtggcga aggccataac gccaacgacc aaggccgtgt16380tgttgctcca ctatggaggt tcgccgggcg aagtcaccga gatcgccggt ttctgccgtg16440aaaagggcct cgtgctcatc gaggacaccg cctgcgcggt ggcatcgtcc gtgcacggca16500ccgcctgcgg aacctttggt gacctggcca cttggagttt cgatgcgatg aagatcctgg16560tcaccgggga tgggggcatg ttctacgcgg cggaccgcga gctggcgcac cgtgcaagac16620gactcgccta ccacggtctt gagcagatga gcggattcga ttcggccaag tcttccaacc16680gctggtggga tatttgcgtc gaagacatcg gccaccggct gatcgggaac gacatgacgg16740cagcgcttgg cagcgtgcag ctgcgcaaac tgccagattt cgtcagcagg cgccgggaaa16800tcgctacgca gtacgaccgg ttgctttccg atgtgccggg tgtccacctg ccgccgacgc16860taccggatgg gcacgtctcg tcacactact tctactgggt ccagctcgct ccggagatcc16920gcgaccgggt agcgcaacaa atgctggaac gcggcatcta cacgagcttc cgctacccgc16980ccctgcacaa ggtccccatc taccgcgccg actgcaagct gccttctgcg gagcacgcct17040gccgcagaac actcctgcta ccactgcacc cgagccttga cgacgccgag gtgcgcacgg17100tggctgacga gttccgcaag gccgtcgagc aacacatcag ctgaagatca ccacgtcgaa17160agtgaggatg tcgcgcgtga gcggcacatt cgaagaactc tcctcggtat acagcccaga17220ccatgccgac atctacgacg cgatccactc cgcgcgtggc cgggactggg caaccgaggc17280
cgaggaaata atccagctca tacgcaccag gctgcccgaa gcacagtccc tactcgacat17340cgcctgtggg accggggcgc acctagagcg gttccgtacc gaatacgcga aggtcgcggg17400gcttgaactg tccgatgcga tgcgggagat cgcgatcaga cgagtccctg aggtaccgat17460tcacactggt gacatccgcg atttcgacct cggcgagcca ttcgacgtcg tcacctgcct17520gtgctttacc gcagcttaca tgcggaccgt tgacgaactg cgacgcgtga cgcggaacat17580ggcccggcac ctggcccctg gcggagtcgc ggtcatcgaa ccctggtggt ttcccgacaa17640gttcatcgac gggttcgtca ccggagccgt cgctcaccac ggcgagcggg tgatcagccg17700gctatcgcac tcggtcctgg agggccgtac gagccgaatg accgttcgct acacagtcgc17760cgaacccgcc gggatccggg atttcacaga gttcgaaatc ctctcgctgt tcaccgagga17820cgagtacacc gccgcgctcg aggacgcagg aatccgcgcg gaataccttc ctggagggcc17880gaacggccga ggcctgttcg tcggaacccg caactgagcc cggaacaaag acgcaaggcc17940ctggctgggc aggccccaga actcactcga gcggtgagcc gacgtgaccc cgggatcact18000tcgatcgtcc ccgatgccgg caagttactg accgccgtga tctaattacc aacaccgtcg18060gacgagttct ggtacctgtt tcggctggtg cagcgaaccg ggaacggggg cgtgttcgcc18120aggggcatca gtgcgattca tagatcgagg agggccgcac cgccgtcgat caagtgcgca18180acctcggtcc accgggactc gtcacgcact tcctcgacag agagctgagc gagtttccca18240ccgttgcgga cctcttcgag caacctcgat ggcgggcacg actcgaggaa agttccgccg18300gcaggagtgg cccggtagcc ccaacgctcg tctaccacag cacggacgac gagatcgttc18360cgttcgcttt tcgagaacgg ctccgggaca gctaccgcgc ggcgggaacc ccggtgcggt18420ggcatccact gtccgggctg gcacacttcc ccgccgccct ggccggctcg caagtcgtca18480tcgcctggtt cgacgagcac ttctccgagc cgcccgcgat cagcgggagg cgatgacagg18540tcgacgagtg gtggcgagcc tttccaacaa cttcacggcc gtgccgcatg cgtcgtactc18600cgcatactca accgccagcc gctgcgcggc ctgccgatac cgaggatctg tcgacatcac18660cttcaccgcc ccagcaacct gctgcggcga cggcctccga gtccgcaaat caacccccgc18720gccactccac gcaacccgag cacacacatc cgttttgtcc tcactacggc cggcaacgac18780caacggcaga ccgtgcgaca acgcctgctg aacggtcccg aacccaccgt tggtcaccac18840cgccgccaac ttcggcatca actctcggta aggcaagaaa gacgccaccc gcgcattgtc18900cggaacataa cccagatcaa cgccttcgcg accggtcgtc gccaccacca gaacttgatc18960gccggccaga cctcgcagcg ctggacggat cagatcatcc gcatccacag ccatcgttcc19020ctgtgtcacc aacaccaccg gacgatcgcc gtccaactcc ccccaccagg acggcaatcc19080
cacccccatc ggcgaatcag gttccaaccg tccaatgaag tgcatctgct gtggcagggc19140tcgcggatac tccaaggatc gcgttccagc ctgcatgaac agatacgggg attcgctgac19200ctctcggctg accggaaccc cgatggaatt ccagaacgcg ttgatcttct tcatccccgg19260atcgtgcacg agcgcattta tcaaccggtt cccgattctg ttccgcagcc ggtggaaggg19320gctggtgccg aacttccatc cagtaccgat gggcggcacc gctggatcgg gcagcagaat19380cggcatctgc gagatcgtgg cccacagaac gccggtaaca gcgtggacca gtttagctgg19440tccccatgac gcatcggcaa gcagcacatc agcccgggtt cggtccacta ctgccacgag19500atcgcgatac tggccttcgt acgccggaac ccagtggttg tccatcaacc agcgtgcccg19560gcgacgcgcg gacatctgga tgctttccgg aaacttctgc tccagctcgc ggccgtcgat19620gaagcgcccc tcgaccggcg cggcgaaatc cgctccggag cgttcaaccg cagcacggta19680gttctcgccc gtgtaccacg tgacctgatg gtcgcgctcc accaaggctc gggaaacagg19740aaccagcggg ccgatatggg cgtgatccgc ataagtagca aacacgaagt gcgccatgat19800ccagtcccaa ctccccaacc accgaggccc gcaatacacg ccaccgtaac agaattgcac19860gaccgccggg tgccgagcga ctcgggggta aagattcagt tggattgccg tgagtggtct19920gcgtgatggc atggcgtgat cgcccgatgg gttcggtgcc ggtcggggtt ggcgcgggtc19980aggctggggt ggggtccggt ggcatccagg ggtgtccgcg aatggcctcg cggagggctt20040cgatcatgtt gcggccgtgc ttgccggcgg tggagaggga tccgcggatt cggtagcggt20100ctttggtgcg tttctcgatg gtcagccgcc cggagatgtt ctgttgcacc ttggcgggcc20160gtaggtcgcg ttcggcttgg ttgggtgtgc gcggccccac tcgcagcggg gtttcgtcgc20220agcagacagc gtaggccagg gtgtggatcc gcttgtcgac ctcggtcaac acgcccgcgg20280cgcgggtaag cacgccgtgc acgaaaccca cgctgggcac ggcgccggtc agcgatgcca20340acagctcgac gcagcggtgt acgggaatga agtgcacgac catgaggtac acagcgaaag20400cctgcaggtt cgggccgtag cccaccgcgc cgggacgggc gccttccggg cgggcagcgg20460tgtgcaccct gccgcagccg cagcgcaccg cgtgctagtc gtactgggtg acctttcacc20520gacaccgggg agatctcatg ctgctggtag cgatccacca cccccagatc ccgtgccccg20580ggccaggtca ctgccgcact cgcatacgcc cccgggaaac cgatccttgt gatctcccgg20640gagatcggtc caggccagat tcgcccccgg cgccccgggc tgcttgccct tccgcttcac20700cgcgccgccg cgtttcgcct tcgccggagg cggtgtcctg cccgggccgt cgtctttgga20760cggagcagat gacgaattct tgctgttacg agacagcgca tgctccagct tcgccagtct20820ctcgcccagt gcctcgttga cctccgccaa ctcggccatc tgcgcggcca tcgctgtgat20880
ctgccggtct cgcaccgcaa tctgctcgcc cagcaccgcg atccgcgcgc cctgctcacc20940cacgagctcg atcaactcgg cgacaccgac acagaaacca caccagctcc agcagacgca21000gagtgccacg ccagcacccc tgtcactaca cacagtgcac cggctgaatg tttacactcg21060gggagttagg accgcgggcg aattcgcaca tagcccagca ccgatgtcag tcgatcaagt21120tatgttccgg gccgcctccg ctctgcccga acccggtcca gtaccgtaac aacacatcat21180ggagataatc ggcagaggat tcatcgcccg caacttgctg cggatctccg ggcggcacgc21240agacgcggtc gcattggcgg ctggcgtgtc gaacaccagc tgccgctccg aggacgagta21300tcagcgggaa gccgccctcg tgtaccggac catcgaacgc tgccacgcta tcggccgcaa21360actactgttc ttctccaccg cgtcagcatc gatgtacgga gcgctcacct caccagggtt21420tgaggacggt ccggtgtacc cgccgaccac ctatggccgt cacaagctgg ccatggaagc21480ggtgatcaag gcatccggag tggactttct catcctgcgg ctggcctacg tcattggagc21540ccaccagcgc ggacaccaac tgctcccgtc cttggtgacc cagctcaggt ccggctcggt21600cacggtgcac cgaggcgcgc atcgcgatgt aatcgcggcg gacgacgtgg tgaccatcgt21660cgacgacctg ctcaccaagg cggtcgcggg gacggtggtc aacatcggct cggggttccc21720cgtcccggcc gagaagatcg tggcacattt ggagtatcgg ctgggaacgg cagctgcacg21780gcagtggatc gaccatccta ccgaatacca gatctcgttg acccggctga acacgctggt21840cccacgaatc gccgagttgg gcttcgggcc ggactattac cggcaggtgc tggaccacta21900cttggacctg tacccacagg cctgatcgat cgtcgtgacg agcacggcct gccggatcac21960cgactcatcc gaatctccag ccaccgcagg gtcatccacg cctgtcccgg ctctgatgtc22020gcgggcggaa gcggtgaccg cgttgcggtc ctgatcttcc gccggcaggg acaactcgtc22080gacgacgccc ttgcgctaga tccggatcac gggttgccac gtggcgggcg gattgaatgc22140ccgatcgatg acaatgccca ccgccgtatt ggccaccgcg cacatcgcgg gcagcatccg22200ccgccaggcg aaggaagccc acccgagaac gccgatgcac cggctttcgc accgaactga22260tcatctcccc gtcgttgacg ttgcccggtt gcatcttggc tgacatgagg cagtgcagca22320ccccgtcgat ctccttgacg agaatgccca cttcgacctg attgtgatcg gttgatgcca22380gcaggtcgcc gcgccgtagt cggtctcgac ctgaagacct tcgaccgtga agaatcgacc22440ttcggcgtga accaggttct cggtggccgc ttcggatttc cagttcacta gggcgctgaa22500cgggatgcgc gtggtctcga agctgttctc gcccaggcga tcggtcagcc agcagttgaa22560ctcagcattc ggcatcagcc gattgcaggt actcagcgct gagttgatga accgctttcc22620gccgagcagc gcatcggtac tcgccccagc ttcaacagag ctgcccctgt ctagtccctc22680
actgccacaa cgatgtgcac gctggctccc aggaatattg gggactgcga gacttccacc22740tggtaatcaa gcttgcggag ccgatcgagc acctggcgca gccgaccgca gatgtcgtgc22800acttccacga ctatccgacg aatacggggc cacatctcgt catcgatccc gttcagcacg22860tcgagctccc cgcgttcgac atcgatcttg agcagatcga gcacatcaag ccggtgctgc22920cttgcgatct ctgtcaacgt ggtcacccgc acgtcgagtt cttccttggt gcggaccagc22980ccctgcatcg attcccccgc cagctcgggg ctgccgacgt tcgacatcac cgtgtcgatg23040ttgcgccgct catccgccgc atcgaggtgc agcgtcgaca aagatggccc tgcggggtaa23100tagacgaagc gggacgttcc gggctccgca cccaccgcca ggtcgaacgt cacacctcgc23160ggtacgtggc gggcgaagtt ttcccgcagg caggcgaagg tcgttggtgc cggttcgtaa23220gcgagtattc gtgctgctgg aattcgatcg gcgaagtaca tcgacgcaag gccgacatgc23280gcgccgacat ccacgatcac cgaatcagca cccaagccgc gcagaccgcg ggcgtaagcc23340gaatcgttcg cgatgtcctg ccaaatggca agtacttcaa gcgtgttggc gcatgcgact23400agacgcccat caggaagggc ctgcgtcgcc ctgtcgtcaa ccgtgtcgaa catcggtaac23460gccccgtcct cagcgattcg gaactcaacg gagttccctt cccagaacaa ttcccgagct23520atattcccga tatctcacgc ggccggcaat ccgaagatca cccaatcacc cttcgcaaca23580atcgaagggg tgagacggaa gtttccgacg gatgacccgt ggtgtagcag caccccgcgt23640gctgcagtcc actcgacgca gtcgtccccg acgggatgat ccgccatcac cacgtgatcg23700ggagggcctc cggcccgcgg gtcattcggc ctcgtttcca gacgacctca tccaccggaa23760ccgcgaagga cagctgcgga aaccgtttga tcagcgtgcc gatcgctacc tgcagctcca23820tcctcgccaa ttgggcgccg atgcagtagt gcgggccgtg ccccagcgcc atgtgcgagt23880tgtgctcccg agccaggtcg agttcgtccg gcccgtcgaa gacggcactg tcacgattcg23940ccgaggctat ctcgaagaac actgcgtcac cccggcgaat cgacactccg cccagttcga24000gatcctcagt cgcgatgcgc gggaacccag gtgtggcacc gagcggcgtg tagcgcagca24060actcctccac cgcgcgcggc accagctctg gatcggcgat cagcttgtca agctggtccg24120gatgggtgag caggttgaag gtgaagtttg cgatgtggtt agcggtggtc tcgaacccgg24180cgatcagcag acccgcgccg gtgacgacaa tctcctcctc gctcagctgg gctccttccg24240ctctggcctg gaccagcacg ctcagcaggt cctcagtcgg catcttcttg cgctgctgga24300ccagttctcc gatatacgcg cgaatttgat cgcggctttc ccgaatctcc tcaggactgt24360tcgatgtgat cgccaacgca atgtccgacc agacccggaa gcgctcgcgg tcggccaccg24420gaatgcccag caagtcgcag atcaccttga tgggcagcgg cagggccagg gctgacacca24480
ggtcgccagg cggcccgtcc gcggccatcc gatcaagtag gtggtcaacg agctgctggg24540tgcgggggcg aagctgttcg actcgacgtg cggtgaacgc cttaccgacc agtttgcgca24600gccgcgtatg ctccggcggg tccatcgttc caagcgaatg ttctcgcaag atcagcggga24660acccccgcgg tacatccctg ttcaggatcg ccgcagcgct gaatcgcgga tcgccgagca24720ctgtcttgat gtccgcatac ctggtgacga gccaaccgtc accaccgtat ggaagccgga24780tcttgctcac cggttcgccc tcacgcaaaa cggcgtagcg atcatccagc aacagccggt24840cgatctcgcc gaagggatag gccattggct catcaccatt ggtcatcaac ggtcccctct24900ctcagacctg gccccgttcc ggggacgcgc ttcgcggagc cagcggtgga ctccacctcg24960attgcgctac ttcctcttgc tagtcagcag tttcccgatc acgaggatcc aacgactcgc25020tccgcggaac tggctcccag tgacgatcac ggaagcaatc cactggtgat gaccgcgagc25080acctcatacc ggggttcggc gaggtagaaa tgcccacccg gcaacacgtg gaggtccatc25140tcagcttcgg tgtgctcgcg ccaggattcc gcgtcatccg gagtgacctt cgggtcggca25200tcccccacga gcacggtgat cgaacaactc accttcgatc ccagcggaca acggtaggtt25260tcaaccgctc ggtaatcatt gcggacggcc gtcaggacca tgcgcagaag gtcctcgtca25320ccgagcaccc aggaggtggt cccgcacagc tgagcgctcg ggatagtggg aagtagaagc25380tagccgagcc gcccgcgtac ggcagcacga ccaaagagac cctggcccgg ggtgcgggat25440ggaaacgttg gatccacaga tcgtcgccgg ttgctaggtc ggtcacacga ttctccctag25500gacggcagcg gaactagcgt cgatcgctga gccagctgcc ggtagcgaac caactttcgg25560agccatccat caccattcgc tgatgtcacg atcttcttgg gaggccggtc ggcgcgcaaa25620cctgctgcga gatcagcact ccatcgggcg acttccgatg ggaaaatcca atctcggaac25680tcaaccgttg actgccgtga ttcaagctgg gcctcttgct ggaagtaact gttgcaggaa25740atacggaagc atagagcatc cggagcatcc ggagcatccg gagcatccgg agcatccgga25800gcatccggag catccggagc atccggccag atctcgaatt gctcgcggtc gacctccgga25860actcccgaca gcagcgagtt gatcaccttt atgggcaaat gtagggccag atcaaggaat25920tgtcaacacc tgtggatcaa gattgttcag gcgacggtgg gtggggcgtg gtcgtcgggg25980cgttcgacga gtttgccgcc ctcgaagcgt gctctggcgc gcaccagcgc gacgagttcg26040ggtgcgttga ccgcgggcca gcgagcctgg gctgactcga tcagcttgaa cgccacggcc26100agcaactcgt cgacatcgtc ggtgatcttg gcgactgcct tggggaactt cgccccgtag26160gcggcctcaa acgccctcac cgtgtccaac acgtgccggc tgtcctcggc attccagatc26220tcgcccaggg ccttcttcgc gccgggatgc gccgatttcg gcagcgcggc gagcacattg26280
ccgatcttgt ggaaccagtg gcgctgctcg cgcgtatcag ggaaagcctc gcggagcgcg26340ccccagaacc ccagtgcacc gccgccgatg gccagtaccg gggcacgcat accgcggcgc26400ttgcagtcac gcagtaggtc agcccagccc aggactcggt ggattcccga tagccgtcgg26460ccagcgcgac gagctccttg cggccgtcgg cacggactcc gatcacgacc agcagagata26520gtttgtgttc ttccaggcgg atgttgacgt gaatgccgtc tgcccgcaga tacacaaagt26580ctacttcgga caaaccacgt tcgttgaaag cacggtgttc ggtcctccac tgctcggtca26640gtttcgtgat caacgtagcg gataacccct tgctgctgcc aaggaattgg cccagcgcgg26700gcacgaagtc tccgctggag agcccgtgta ggtacagcag cggcagcatt tcggtgatct26760tcggggtctt gcgcgcccac ggcggcagga tcgccgagga aaaccgccga cgcgcgccag26820tgtccgggtc ggtgcgcttg tcgttgactc gtggcgcagt gacctccacc gcgccagcgc26880tggtcaacac ctcacgaggc tggtcatggc cgttgcggac caccaggcga tggccgcact26940catcgcgctg atcagcgaac tacgcgatgt aggcatccac ctccgcctgc aacgcctcgg27000ccagcatccg gcgggcaccc tcacggacaa tctcatcgat caacgacgcc aaagctgcgg27060caggacggcc gtcgtcacgg gaatcagggt cggggactac gctgagcatc gggtcgtacc27120ttcccgaccg acgcggcaac gtcggccatg cttggaacct tgcatccgat cactgggaag27180gtacgcccct cctcagccga tccaaggttc cgagcattcc tcgaccagat ccgaaagaag27240gtcgacttgc gcaacggcgg cacgcaggac caactcggac tccgcctcaat cctgaccag27300tgcacgggca ctcgatcgga tggactgctc ctgtggctgc gagattttgg atatctttga27360cagaagagca ctttcgcgga tataggctga tccgatggct cgatcgaaac ccccacacgt27420cccgacagga aggcttggcc tttgaagact cacgacgccg cgtccggaac gacggccacc27480gtacaactcc agcgaatcat cggagggcac ttggcctacc acgtccttgg cgccgccgct27540cgattggaca tagccgacca tctgcgcgaa ggcccgctca cggcttccga gttgagcgac27600ctcatcggcg gcgacgatcc cgaaatagtt gacaaattcc tgcgagtggc cgaaacgatc27660ggtctggtgc gcaggaccag ctccggtcag ctggcggaga ccgaactgct cgctctgctg27720cggcgcgacg gggggcggta tcggagtacc gtcctggccc tcacagcccc gggtttcaac27780cgccccagcg agatgatgca ccgcgcagtg ctcagcggca gggcgcatac cgcgcaggtg27840ctgggcactg atctgtgggg ttactacggc accaaccccg aagaagccaa atggttcggc27900ggcgccatga ccgacctgac caacttggtc gcagacctgg tgctggcccg gtacgaattc27960tccggacgcg gcacgatcat ggatgtcggc ggcagccatg gcatattcct gtcccggatc28020ctgcacgccc aaccggacgc gaagggtgtg ctgttcgacc gcatggaggt ggtcgaagaa28080
gcccgcaatc acctagatca ggacatccga acccgcatcc agatcgtcgg cggaaacttc28140ttcgagggag ttcccgaagg cggggatctc tacatcctga agagcgtgct gtgtgactgg28200gacgaccaga gctgcctgca aatactctcc cgcatccgga acgccgccat gcccggtgct28260tcgctactga tcgtcgactg gttgtaccct gacgagtccg accccggctt ggacgcgatc28320tacctccagc aggcgatctc ggtcaacggc cgggtccgca accaggaaca gttcgaatct28380ctcctaaagg caacaggttt cgcggtcacg agggtcgaac gaaccactcc ggagaactgg28440atcccggcga caatcatcga agcgatccgc cggtgatgac cgcgagcacc tcctcctggt28500gttcggcagg cagaagtggc ctgcgggcaa gaccgggagg tgcactccat tgtctcgtct28560atgaaccttg atcgggttat tgatcattag ctgttgggtg tcgggcaggc ttgctcggga28620aggtcaagac tggtggaggt ggtggatgcc tgtcggggct tcctcccacg gtagttgatc28680gctggcttcg gttcctcgct tcgtgctgat gagagtgcac gggtcgatgt ccggggtgca28740ggcggttcca gcgtgtcggt ctaccgatgc tctggtgttg gccgtttcgg gtagagccgg28800gtcatcgcgt ggatcgtgtc ggtcatgcgt gcgaccagtt cggcgggagc gagcacctgg28860acgtccgggc cgaggcgggg gtgtcaggtg ggttgtgtac aagatccgat agttgatgga28920gtacgcagat ggccacgact gatcagcagc aggaagggaa tccgttcggg cggccgccgg28980gcagccggga tcggcgcggg acgcggtcaa cgagatggtc gacgcgggcc tgcttgacgg29040gatgatggac gccatcgatc gggatgggct ggcgttgacc gggcagggtg ggttcctgcc29100tgagctggtc aaggccgtgctggagcgcgg tctacggacc gagatctcgg aacatctcgg29160ctatgacaag ggcgatccgg ccgggcgggg cagcccgaac tcccgcaacg gcaccagcgc29220caagaccctc tcgaccgagg tcggcgacgt ggacttggac gtgccccgcg accgcaacgg29280cagtttcgag ccgcggctgg tcccgaaggg ctttcgccgg gctggcggcc tggacgagat29340catcatcatc tcgctgtacg cgggcgggat gaccgtccgc gacatccagc accacgtgca29400gcgcacctac ggaaccgagc tctcgcacga gacgatctga accgtcgcgg tttcggtaga29460ggcgttgatg tgccccggcg ccggcggagt caggttactc gatcatcgtc atctcagtgc29520cccgactgga ggttgcctcg catgccccgg agatacccac cggagttccg ccgtgggaat29580ggatcaccgg cggcgaaagg ctgatgacca acggactgtc ctttcccctt gctggaaacc29640ctcaacgcct acctctcgaa ccaacgctca tggcagcgca ccagcgcgac actccacgtc29700caccggcaaa ccgtcctcta ccgcatacgc aagatcgaag agctcaccca ccacgacctc29760agcgaaacaa gcgacattgc cgaactgtgg ctggcgctgc gcgcactcga actcatctcc29820cagtgagtgc ctgctgatct cggggaagcg aacgcggtat ttagccgaag tcgcgtctgc29880
tgaccgcgca aaccccgtgc cccgcggagc ggtgaacgtg cgaggtctcg gctactcttc29940tggagttccc aaagccgctg cgggcaagtt ccgcgacatg accggagctt tcgtacccgc30000tgcccgtgcg ttacggctgg gccaacgccg cccaggtcct gcaccggacg acccgcgtcc30060acgcccaggc cacccgtcgg gtcgtggaga ccacccagtt cctgcaggac gtacacgtac30120aggccgacgg tgggctgcca acccccgagg gccacgggat gcggtcggcg cagaagatcc30180ggctgctcca cgccacccat ccgatacttc ctgcggacca gcgacgactg ggactcggca30240gtgctcggcc tggccgcgaa ccaggaagat ctggccgccg ccatgggcac cttctccgtg30300tgcctgcccc gggggctggt ggcgctcggc gtggacctgc ccgaccacga ccgcgacgac30360tgcttccacg tctggtcggt cgtcggccac ctactcggcg tcgacccgca acttatgccc30420gccgggatcg acgaaggggt cgctctgatg gagcggatct ggggccgcca gaccgcggaa30480tccgacgccg ggaaggtctt caccgccgca ctggtgtagt ccgtgcgtaa tgtgctcggt30540cccgcgctgc acggcacccc atcgaggcga tgatcccgcg cttctgcggc gacgagttcg30600ccgacctgct cgccgtcgac cccgcggacc ggaccgccct cgctgccggc cgcgcctcaa30660ccgtcaacac ggtctacggc aagaccggcg accacagcga actcgccgcg tcgatcgcca30720gcaggattgg cgagcttctc ctcgacgccc gccctccaca cggccaaccg cagcaaccgc30780tacgactgga ccattcccaa ctgcgaacaa cagcaccgcg aaggctcgcg atgaacacca30840cagctattga tcgggaactt ataggtgtga tcttcgttgt tctggcatga tcgctggtgt30900gcgggacgcg cggaggttgt cgcctgaggc gcaggaggat ttgcggcgca gggtggtcgc30960tgctgttcat ggtgggatga gtcaggtcga ggcggcccgg gtgttcgcgg tggccccgca31020gtcggtgtcc agatgggtgc aggcgtggcg gaaacgtggc tcgaagggtc tcaccgggcg31080tcgccggggt cgcaagcccg gcgagcagaa agcgttgagt gcccgccggc agcgcaagct31140gcggtatgcg gtggccgagc acaccccggc cacgttcggg ctgaccggcc tggtgtggac31200ccgcaagaca gtggccgagc tgatccgggt gcgccacggc atcgtgttga acctgcgcac31260cgtcggcaac tacctgcgtt cctggggatt gtcgccgcag aaaccgatcc gcaaggccta31320cgaacaggac cccgagtccg tacgccgatg gctggaggag gactacctgg ccatcgccgc31380ccgcgcccgc cgcgagggcg cactgatcct gtggctggac cagaccggga tccgctccga31440cgccaccgta gcccgcacct gggcaccggc gggccagaca ccggtggtgg gcaaaacggg31500caaacgattc agcgtgaacg cgatgtgcgc gatcgggaac aaaggcgagc tgtacttcac31560cgtctacacc ggctcgttca acggcaaggt gttcctgtcg ttcctggacc ggctgacccg31620ccatctggac cgcaaggtcc acctgatcgt tgacggacac cccgtccacc gccgcaagac31680
catccagcaa tggatcacca agcacgctga ggcgatcgcg atgcacttcc tgccgggata31740cagccccgaa ctcaaccccg acgagctact caatgccgac ctcaaacgca ccgtttccac31800cagcacagcc cccaaaaccc gcgccgagtt gaaacaagcg gtccgctcct tcctccaccg31860gctccagaag ctgcccgacc gagttcgctc ctacttcggc aaacccgaag ttcgctacgc31920cgcctaacat cacacatttg ccacccggat caataacatc ccttttccag gtcgtagtgg31980accgaccccg tcaggcaagt gcgagttcct tcggccctag gcacacgtcc aactctgcca32040gcgtctcgtc gttcacgtcg accgggcgca gcgtgtgcgg cagcgagcgg acggcgtcag32100cggcgatgaa cgcgtcctgg gtagtggtcg gcgatccgtc gcatggccga accggtgccc32160gcaggcccgg gcaaccattc gacgcctcac cataaaccgt ctggtgacgc tcaaaggggc32220gacgcgacag aacccagatc gcaccgccgc aacaccgcgg tccgtgccag cagccgcatg32280ttcgcccggg accagccgta tccaggccgt gcagcgtcgg gtggtcagga actctgaccg32340cggagtactc ctcccgtgtt gtcaacggaa gagctgtcgc ctggtcagcg cggatcgttc32400acttagatgg cggtttctgt taccacaagt gaagatttgc aggcttcgag gatgcgcgat32460gccggcagcg gatcacactt cttgacctga ccgcctcgag atcgtttctc tattctcagg32520ccgtgcggct gagccgctga ccgggcatgt agatcgaaag gcgggctatg cacgcttact32580actgtgcgaa gtgcaagaac gaacaaacag atcctgcgga tgcgctgaag ttcgcggcct32640cgatcggctt ggaattgtgg ctgccgaagg atgaggtgac gttcgacttt ccccacggcg32700cgcagcagtg ccagacggcg atcgagaaag cggaatgtgt gatctgccag cctccgatag32760gcaacgactg ctcctgggaa ctcggatacg ccatcgggat cggcaaacca gtctacgtca32820tcggaacgct ggccgagcag gactggatga ccaagctcgg cgtcactcac gtggacccgg32880cgtcgttggc tgccgagaaa gaatgaggtc ctgccgtgac tcagcacagt cggcggccca32940ccggcaaagc agtggggcgc cgcagagtag cggcgatcga ctgcgggacg aactcgatcc33000ggatgctggt tgccgacctc ggtgccgacg ggcatttgac ggaagtcacg aaacggttcg33060acatcgtccg tttgggtcag agagtcgacg aacacggctc gatctcccgc gaatccttcg33120aacgagcgcg cgccgtgttg gccgaatacg caggaaccat caccacggcc agtgtggagc33180gcgtgcgcat gtgcaccaca tggatctccc gacgagcgtc caacaacgac gaattccgca33240cactggtcca agagacactc ggctgcgcac cggaagacat caccagcgac gaggaagcac33300ggctcgcttt cgccggggct accagcggtc ttccgcaggc gagctacctg gtcgccgaca33360tcggtggcgg gtccacacag ctcgcgctgg gaacagcagg tttcgtggac agatccgtct33420ccgtcggcct gggctgcgta cgcctgaccg aacgccacct gcggtcggat cctccagcct33480
cgggcgaact cgcggcggta caggacgaga tcacggcact ggccgaccag gcactggccg33540aacttcccga tttgtcgggc actcggcttc tcggtgtctc cgaagcagtc ggcacagttg33600ccgccatcgc gcttcctgga cgaaggctcc atcacgcacg aatgacctac gaccaggtcg33660attacgtgac agagcgggtg ctgggaatgt ccttcgccca gcgacaagcg ctgcccggaa33720tccacacagg tatggccgat gtactacccg tcagcgcgct cagcgtgcgt acggtgatgc33780aatgtgcccg ggccaaggag ctgatcatca gcgagcacga catcctgcat ggaatcgctt33840actccctgag ataagcggga tcagatccca atgccgaaca gcatcacggc gagcgggcaa33900tcgaatccac cgacgcaccg agtcccgaac accctgccag cccggcaggg tgttcggcgg33960cgggtgtcag gtctgccgcc acgggcttcc ggcgcctctg atggacgcct agccgcaaac34020ctttgcgtag tcggtttcct cgaccgcttc catcctcata caccacgaca ggcgcgaaaa34080cgtatgccgc gaaggtctcg catgcctcgc gtatgtcggc ctcggcgtgg agttaggcaa34140acgagttgcc aaggcagagg atcacgtcag aggtgacacc atgcgaaggt gcccagacat34200ggtgccgaag atgccgcgct actcgcgagc atcttcggca ccttcgcctt ccagcaccca34260ctcccacgcg ccgctggcga aaccggcttt tcatcgaacc agcacgaaca ccagcaggct34320cagaccacag cccagcacga acacggcata gaggatgtcg acaccgtgcg ggggatgctc34380ggctatgccg gccacgatcg ccgccgccgg caaccaggcg agcagcagca cacatgtcag34440cctgttgcgg cggacccgca tcccggagcg cgacgaccac ggtcgcggtg accacccacc34500ggtcagccag ggcggcagcc gccggacgaa caccaggacc agcgtgcagg cgaagcccag34560agccagaccg atcacggtcg tcgacgtcca gccaccagcg aggtggatcg cggcgagtac34620agcgaagacc ccaaggaacc accagcgcgg acgccaggca acgtcctcgg ccgccacctc34680ggccggctcg ggaacaggcg acttttcggc cgctgattca gctccgtcgg aaaccaccac34740accacccttg cccaaacaga cctgccgata gcgtatcgag cgcgatctga gcactctcgc34800gccgaagggc accacagcag ggagtccccg cgccccactg cgctggctgg ccggcgactt34860cgggttgcgt gatctcgtcg ccgacagcgg aaacacagca gccatcgccg catatgaaca34920ggccactgct caggcagcag aggcaaaact agatggcaac gctgcgcgac gcagcgacgt34980catgtcccgg gacaccgtca caagcagcga cacgctgtcg agtgcgggat caaccgcctc35040aaacggaacc gagccgtggc caccagatac gacaagcttg ccgtccgcta cgagccaccg35100tcaccatcgc agggatcaac gagtggctcc catgactttc gaaacaggcc caagcgcccg35160ccgcctggtc caagccccgg cgcgcgacag ccacacccga actcgcgttg tcgcggttgg35220gaatacccac aaccggctct ccgcgcgcgg ggcgccccag caacggcgcc ccgacacggt35280
gctgcgtgga acggacgaga gtgcgctccg acgccagccc cgagcacctg tgcggttcga35340gcccgcggac gaactgcggc tctccgtcct gtcctcgctg atccccgccg ccgctgggcg35400caggtcttcc cagacacgcc gagcacactg atggcctggc accgcacgct tgtggcccgc35460cggtgggact actccgatcg gcgccgacct ggacgaccgc ccacaaggcc ggccatcaag35520aagctcgtgc tacgcctcgc ccgcgaaaac agtcagtggg gacaccgccg gatccggggc35580gaactggccc ggctcggaca cccgatcgcc gcctccaccg tctgggaaat cctgcacgta35640ggcggcatcg atccggcccc gcgccacagc ggcccgacct ggcgtgagtt cctgtccgca35700caagccagcc gtctgatcgc ctgcgacgtc ctgagcatcg acaccaccgg cctacaacgc35760ccatactccc tggtcttcct agaacaccga acgcggcgcc tgcacatcac cggcgtcacc35820gcacacccga cggcgcctgg gttactcagc aagcgcgcga cgtcgccacc gacctcggca35880cgcgtatgga ctcgctgcgt ttccgcaccg gagaccgcaa acagcaagta caccgacgat35940atcgagatca tcaagacacc ggcgcgggcg ccacgagcga atgtgcactg cgagagagcg36000atcggcagcc tccatcgaga agtcctcgac cactcccctc atcatcggta agacccatgc36060acgccgcgtt ctcaccgagt accaagagca ctacaacaaa caccgccccc accgggcccg36120caactagaac tagtgtcctg cgccggagat tcgttgacaa tatgatcgga gtgactccaa36180gatctcgtca gcgctcttcg tccagatgaa cggccgggga tcgttgttcc actcgtcgat36240ccagttgcgg atatcggcct cgagtgcctg gacgctggtg tgcacgccgc gttgcaggag36300tttggtggtc aattcgccga accagcgttc gacctggttg atccaggacg atccggcggt36360gcgatagcgc gccgatcggg tccttcgcgg ggaactccgg ggattccgtg ggccaccacg36420ccacgaccgg cgcgtccggc agcagcagcg gcaccaccga gccggcgccc tcgtcggcca36480gcggcccgta cagccgcagc acgatgacct ccgaggcccc agcgtcgccg ccgatgcg 36538<210>3<211>4344<212>PRT<213>刺糖多胞菌 NRRL30141<400>3Met Ser Glu Ala Gly Asn Leu Ile Ala Val Val Gly Phe Ser Cys Arg1 5 10 15Leu Pro Gln Ala Pro Asp Pro Ala Ser Phe Trp Arg Leu Leu Arg Thr20 25 30Gly Thr Asp Ala Ile Thr Thr Val Pro Glu Gly Arg Trp Gly Asp Pro35 40 45Leu Pro Gly Arg Asp Ala Pro Lys Gly Pro Glu Trp Gly Gly Phe Leu
50 55 60Ala Asp Val Asp Cys Phe Asp Pro Glu Phe Phe Gly Ile Ser Pro Arg65 70 75 80Glu Ala Ala Ala Met Asp Pro Gln Gln Arg Leu Ala Leu Glu Leu Ala85 90 95Trp Glu Ala Leu Glu Asp Ala Gly Ile Pro Ala Gly Glu Leu Arg Gly100 105 110Thr Ala Ala Gly Val Phe Met Gly Ala Ile Ser Asp Asp Tyr Ala Ala115 120 125Leu Leu Arg Lys Ser Pro Pro Glu Val Ala Ala Gln Tyr Arg Leu Thr130 135 140Gly Thr His Arg Ser Leu Ile Ala Asn Arg Val Ser Tyr Val Leu Gly145 150 155 160Leu Arg Gly Pro Ser Leu Thr Val Asp Ser Gly Gln Ser Ser Ser Leu165 170 175Val Gly Val His Leu Ala Ser Glu Ser Leu Arg Arg Gly Glu Cys Ala180 185 190Ile Ala Leu Ala Gly Gly Val Asn Leu Asn Leu Ala Ala Glu Ser Asn195 200 205Arg Ala Leu Met Asp Phe Gly Ala Leu Ser Pro Asp Gly Arg Cys Phe210 215 220Thr Phe Asp Ala Arg Ala Asn Gly Tyr Val Arg Gly Glu Gly Gly Gly225 230 235 240Leu Val Val Leu Lys Lys Ala Asp Gln Ala Arg Ala Asp Gly Asp Arg245 250 255Ile Tyr Cys Leu Ile Arg Gly Ser Ala Val Asn Asn Asp Gly Gly Gly260 265 270Ala Gly Leu Thr Ala Pro Ala Ala Asp Ala Gln Ala Glu Leu Leu Arg275 280 285Gln Ala Tyr Arg Asn Ala Gly Val Asp Pro Ala Ala Val Gln Tyr Val290 295 300Glu Leu His Gly Ser Ala Thr Arg Val Gly Asp Pro Val Glu Ala Ala305 310 315 320Ala Leu Gly Ser Val Leu Gly Val Ala Arg Arg Pro Gly Asp Lys Leu325 330 335Arg Val Gly Ser Ala Lys Thr Asn Val Gly His Leu Glu Ala Ala Ala340 345 350Gly Val Thr Gly Leu Leu Lys Thr Ala Leu Ser Ile Trp His Arg Glu355 360 365Leu Pro Pro Ser Leu His Phe Thr Ala Pro Asn Pro Glu Ile Pro Leu
370 375 380Asp Glu Leu Asn Leu Arg Val Gln Arg Asp Leu Arg Pro Trp Pro Glu385 390 395 400Ser Glu Gly Pro Leu Leu Ala Gly Val Ser Ala Phe Gly Met Gly Gly405 410 415Thr Asn Cys His Leu Val Leu Ser Asp Ser Ser Gln Val Glu Arg Arg420 425 430Arg Ser Gly Pro Ala Glu Ala Thr Met Pro Trp Val Leu Ser Ala Arg435 440 445Thr Pro Val Ala Leu Arg Ala Gln Ala Ala Arg Leu His Thr His Leu450 455 460Asn Thr Ala Gly Gln Ser Pro Leu Asp Val Gly Tyr Ser Leu Ala Thr465 470 475 480Thr Arg Ser Ala Leu Pro His Arg Ala Ala Leu Val Ala Asp Asp Val485 490 495Pro Lys Leu Leu Ala Gly Leu Lys Ala Leu Ala Asp Gly Asp Asp Ala500 505 510Pro Thr Leu Cys Thr Gly Thr Thr Ser Gly Glu Arg Ala Thr Val Phe515 520 525Val Phe Pro Gly Gln Gly Ser Gln Trp Ile Gly Met Gly Arg Gln Leu530 535 540Leu Gln Thr Ser Glu Val Phe Ala Ala Ser Met Ala Asp Cys Ala Asp545 550 555 560Ala Leu Ala Pro His Leu Asp Trp Ser Leu Leu Asp Val Leu Arg Asn565 570 575Ala Ala Gly Ala Ser Gln Leu Asp Arg Asp Asp Val Val Gln Pro Ala580 585 590Leu Phe Ala Val Met Val Ser Leu Ala Glu Leu Trp Arg Ser Trp Gly595 600 605Val Arg Pro Glu Ala Val Val Gly His Ser Gln Gly Glu Ile Ala Ala610 615 620Ala Cys Val Ala Gly Ala Leu Ser Val Arg Asp Ala Ala Arg Val Val625 630 635 640Ala Val Arg Ser Arg Leu Leu Ala Ala Leu Ala Gly Arg Gly Ala Met645 650 655Ala Ser Leu Gln His Pro Val Glu Glu Val Arg Gln Ile Leu Leu Pro660 665 670Trp Arg Asp Arg Ile Gly Val Ala Gly Val Asn Gly Pro Ser Ser Thr675 680 685Leu Val Ser Gly Asp Arg Glu Ala Met Ala Glu Leu Leu Ala Glu Cys
690 695 700Ala Arg Arg Glu Leu Arg Met Arg Arg Ile Pro Val Glu Tyr Ala Ser705 710715 720His Ser Pro His Ile Glu Asp Val Arg Asp Glu Leu Leu Ala Leu Leu725 730 735Ala Ser Ile Glu Pro Arg Thr Gly Asn Ile Pro Val Tyr Ser Thr Thr740 745 750Thr Gly Glu Leu Leu Asp Arg Pro Met Asp Ala Asp Tyr Trp Tyr Arg755 760 765Asn Leu Arg Gln Pro Val Leu Phe Glu Ala Ala Val Glu Ala Leu Leu770 775 780Lys Arg Gly His Asn Ala Phe Ile Glu Ile Ser Pro His Pro Val Leu785 790 795 800Thr Ala Ser Ile Gln Glu Thr Ala Ala Arg Ala Gly Arg Glu Val Val805 810 815Ala Leu Gly Thr Leu Arg Arg Gly Glu Gly Gly Leu Arg Gln Ala Leu820 825 830Thr Ser Leu Ala Lys Ala His Val His Gly Val Ala Ala Asn Trp His835 840 845Ala Val Phe Ala Gly Thr Gly Ala Gln Arg Val Asp Leu Pro Thr Tyr850 855 860Ala Phe Gln Arg Gln Arg Tyr Trp Leu Asp Thr Lys Pro Ser Asp Leu865 870 875 880Ala Met Pro Glu Gly Asp Val Ser Thr Ala Leu Arg Glu Lys Leu Arg885 890 895Ser Ser Pro Gly Ala Asp Val Asp Ser Ala Thr Leu Thr Ile Ile Arg900 905 910Ala Gln Ala Ala Val Val Leu Gly His Ser Asp Pro Lys Glu Met Asp915 920 925Ser Asp Arg Thr Phe Lys Asp Leu Gly Phe Asp Ser Ser Thr Val Val930 935 940Glu Leu Cys Asp Arg Leu Asn Ala Ala Thr Gly Leu Arg Leu Ala Pro945 950 955 960Ser Val Val Phe Asp Cys Pro Thr Pro Tyr Lys Leu Ala Arg Gln Val965 970 975Arg Thr Leu Leu Leu Asp Glu Pro Val Pro Thr Thr Ser Pro Arg Thr980 985 990Glu Thr Glu Ala Asp Glu Pro Ile Ala Val Ile Gly Met Gly Cys Arg995 10001005Phe Pro Gly Gly Val Ser Ser Pro Glu Glu Leu Trp Gln Leu Val
101010151020Ala Ala Gly Arg Asp Val Val Ser Glu Phe Pro Ala Asp Arg Gly102510301035Trp Asp Pro Glu Arg Ala Gly Thr Ser His Val Arg Ala Gly Gly104010451050Phe Leu His Gly Ala Thr Asp Phe Asp Pro Gly Phe Phe Gly Ile105510601065Ser Pro Arg Glu Ala Leu Ala Met Asp Pro Gln Gln Arg Leu Leu107010751080Leu Glu Ile Ala Trp Glu Ala Ile Glu Arg Gly Gly Ile Asn Pro108510901095Gln Thr Leu His Gly Ser Gln Thr Gly Val Phe Val Gly Ala Thr110011051110Ser Leu Asp Tyr Gly Pro Arg Leu His Glu Ala Ser Asp Glu Ala111511201125Ala Gly Tyr Val Leu Thr Gly Ser Thr Thr Ser Val Ala Ser Gly113011351140Arg Val Ala Tyr Ser Phe Gly Leu Glu Gly Pro Ala Val Thr Val114511501155Asp Thr Ala Cys Ser Ser Ser Leu Val Ala Leu His Leu Ala Cys116011651170Gln Ser Leu Arg Ser Gly Glu Cys Asp Leu Ala Leu Ala Gly Gly117511801185Val Thr Val Met Ala Thr Pro Gly Met Phe Val Glu Phe Ser Arg119011951200Gln Arg Gly Leu Ala Pro Asp Gly Arg Cys Lys Ser Phe Ala Glu120512101215Ala Ala Asp Gly Thr Gly Trp Ser Glu Gly Ala Gly Leu Val Leu122012251230Leu Glu Arg Leu Ser Asp Ala Arg Arg Asn Gly His Asp Val Leu123512401245Ala Val Val Arg Gly Ser Ala Val Asn Gln Asp Gly Ala Ser Asn125012551260GlV Leu Thr Ala Pro Asn Gly Pro Ser Gln Arg Arg Val Ile Thr126512701275Gln Ala Leu Ala Asn Ala Lys Leu Ser Val Ser Asp Val Asp Ala128012851290Val Glu Ala His Gly Thr Gly Thr Arg Leu Gly Asp Pro Ile Glu129513001305Ala Gln Ala Leu Ile Ala Thr Tyr Gly Gln Gly Arg Gly Pro Glu
131013151320Arg Pro Leu Trp Leu Gly Ser Val Lys Ser Asn Ile Gly His Thr132513301335Gln Ala Ala Ala Gly Val Ala Gly Val Ile Lys Met Val Met Ala134013451350Met Arg Tyr Gly Glu Leu Pro Ala Thr Leu His Val Asp Glu Pro135513601365Ser Ser Gln Val Asp Trp Ser Ala Gly Met Val Gln Val Leu Thr137013751380Glu His Val Pro Trp Pro Asp Asn Ser Arg Pro Arg Arg Val Gly138513901395Val Ser Ser Phe Gly Ile Ser Gly Thr Asn Ala His Val Ile Leu140014051410Glu Gln Ser Pro Thr Ala Ser Ser Glu Phe Val Glu His Ser Gly141514201425Pro Asp Ser Glu Ser Ala Val Asp Val Pro Val Val Pro Trp Val143014351440Val Ser Gly Lys Thr Pro Glu Ala Leu Ser Ala Gln Ala Asp Asn144514501455Leu Val Ser Tyr Leu Asp Asp Arg Pro Asn Val Ser Ala Leu Asn146014651470Val Ala Tyr Ser Leu Ala Ser Glu Arg Ala Ala Leu Asp Glu Arg147514801485Ala Val Val Leu Gly Ala Asp Arg Glu Ala Leu Leu Ser Gly Leu149014951500Lys Ala Leu Ala Ala Gly His Glu Asp Pro Gly Val Ala Ser Gly150515101515Ser Leu Val Ser Gly Gly Val Gly Phe Val Phe Ser Gly Gln Gly152015251530Gly Gln Trp Ser Gly Met Gly Arg Gly Leu Tyr Arg Ala Phe Pro153515401545Val Phe Ala Ala Ala Phe Asp Glu Ala Cys Ala Glu Leu Asp Ala155015551560His Leu Gly Gln Glu Val Gly Val Arg Asp Val Ala Phe Gly Ser156515701575Asp Ala Gln Leu Leu Glu Arg Thr Leu Trp Ala Gln Ser Gly Leu158015851590Phe Ala Leu Gln Val Gly Leu Leu Arg Leu Leu Gly Ser Trp Gly159516001605Val Arg Pro Gly Ala Val Leu Gly His Ser Val Gly Glu Leu Ala
161016151620Ala Ala His Ala Ala Gly Val Leu Ser Leu Pro Asp Ala Ala Arg162516301635Leu Val Ala Gly Arg Ala Arg Leu Met Gln Ala Met Pro Asp Gly164016451650Gly Gly Met Leu Ala Val Ala Thr Ser Glu Thr Gln Val Glu Pro165516601665Met Leu Asp Gly Val Arg Asp Arg Ile Gly Ile Ala Ala Ile Asn167016751680Ala Pro Glu Ser Val Val Leu Ser Gly Asp Arg Glu Leu Leu Ala168516901195Glu Val Ala Asp Gln Leu Asn Asp Gln Gly Cys Arg Thr Arg Trp170017051710Leu Gln Val Ser His Ala Phe His Ser Tyr Arg Met Glu Pro Met171517201725Leu Asp Glu Phe Ala Gln Ile Ala Gly Ser Val Asp Phe Arg Arg173017351740Cys Glu Leu Pro Ile Ile Ser Thr Leu Thr Gly Asn Leu Asp Asp174517501755Val Gly Val Met Ala Thr Pro Glu Tyr Trp Val Arg Gln Val Arg176017651770Glu Pro Val Arg Phe Ala Asp Gly Val Gln Ser Leu Val Glu Gln177517801785Asp Val Ala Thr Val Val Glu Leu Gly Pro Asp Ala Ile Leu Ser179017951800Ala Leu Ile Pro Asp Cys His Ser Trp Gly Asp Gln Thr Val Pro180518101815Ile Pro Leu Leu Arg Lys Asp Arg Ala Glu Pro Glu Thr Val Val182018251830Ala Ala Val Ala Arg Ala His Thr Arg Gly Val Gln Val Asp Trp183518401845Ser Ala Phe Phe Ala Gly Thr Gly Ala Gly Arg Val Glu Leu Pro185018551860Thr Tyr Ala Phe Gln Arg Gln Arg Tyr Trp Leu Glu Ser Ser Val186518701875Ser Gly Asp Val Thr Gly Ile Gly Leu Ala Gly Ala Glu His Pro188018851890Leu Leu Gly Ala Val Val Val Leu Ala Asp Gly Asp Gly Met Val189519001905Leu Thr Gly Arg Leu Ser Val Gly Thr His Arg Trp Leu Ala Glu
191019151920His Arg Val Leu Gly Glu Val Val Val Pro Gly Thr Ala Ile Leu192519301935Glu Met Val Leu His Ala Gly Ala Arg Val Gly Cys Gly Arg Val194019451950Glu Glu Leu Thr Leu Glu Ala Pro Leu Val Val Pro Glu Arg Asp195519601965Ala Ile Glu Ile Gln Leu Leu Val Asn Ala Pro Asp Asp Lys Gly197019751980Arg Arg Ser Val Ser Leu His Ser Arg Pro Ala Gly Gly Ser Gly198519901995Gly Gly Gly Trp Thr Arg His Ala Thr Gly Glu Leu Val Val Ala200020052010Gly Thr Gly Gly Gly Ala Val Thr Gly Trp Ser Thr Glu Gly Ala201520202025Glu Pro Val Ala Leu Gly Glu Phe Tyr Val Val Gln Ala Gly Asn203020352040Gly Phe Glu Tyr Gly Pro Leu Phe Gln Gly Leu Arg Ala Ala Trp204520502055Arg Arg Gly Gly Glu Val Leu Ala Glu Val Ala Leu Pro Ala Ala206020652070Ala Gly Ala Met Ala Gly Phe Leu Ile Asn Pro Ala Leu Leu Asp207520802085Ala Ala Leu Gln Ala Ser Ala Leu Gly Asp Arg Pro Ala Glu Gly209020952100Gly Ala Trp Leu Pro Phe Ser Phe Thr Gly Val Glu Leu Ser Gly210521102115Gln Gly Gly Thr Ile Ser Arg Ala Arg Val Glu Ser Thr Arg Pro212021252130Asp Ala Val Ser Val Ala Val Met Asp Glu Gly Gly Arg Leu Leu213521402145Ala Ser Ile Asp Ser Leu Arg Leu Arg Pro Val Ser Ser Val Arg215021552160Leu Ala Asn Arg Asp Val Val Gly Asp Ala Leu Phe Glu Val Thr216521702175Trp Glu Pro Val Ala Thr Arg Ser Thr Val Ser Gly Arg Trp Ala218021852190Leu Leu Gly Asp Ala Val Gly Gly Met Ala Gly Leu Ile Gly Leu219522002205Ala Pro Gly Ser Val Asp Arg Cys Ala Gly Leu Ala Glu Leu Ala
221022152220Gly Asn Leu Asp Ser Gly Ala Leu Val Ala Asp Val Val Val Tyr222522302235Cys Ala Gly Glu Gln Ala Asp Pro Asp Ala Gly Val Ala Ala Leu224022452250Ala Glu Thr Arg Glu Met Leu Ala Leu Val Gln Ser Trp Leu Ala225522602265Glu Glu Arg Leu Ala Gly Ser Arg Leu Val Val Val Thr Cys Gly227022752280Ala Val Thr Thr Ala Ala Gly Asp Gly Ala Ser Lys Leu Ala His228522902295Ala Pro Leu Trp Gly Leu Leu Arg Ser Ala Gln Ser Glu Asn Pro230023052310Gly Arg Phe Val Leu Val Asp Val Asp Gly Thr Ala Glu Ser Trp231523202325Arg Ala Leu Pro Ser Ala Val Gly Ser Met Gln Pro Gln Leu Ala233023352340Val Arg Lys Gly Val Val Thr Val Pro Arg Val Ala Ser Val Pro234523502355Gly Pro Val Glu Val Pro Ala Val Val Ala Gly Pro Asp Arg Thr236023652370Val Leu Ile Ser Gly Gly Thr Gly Leu Leu Gly Gly Val Val Ala237523802385Arg His Leu Val Ala Glu Arg Gly Val Arg Arg Val Val Leu Thr239023952400Gly Arg Arg Gly Trp Asp Ala Pro Gly Ile Thr Glu Leu Val Gly240524102415Glu Leu Glu Gly Phe Gly Ala Val Val Asp Val Val Ala Cys Asp242024252430Val Ala Asp Arg Ala Gly Leu Glu Gly Leu Leu Ala Ala Val Pro243524402445Ala Glu Phe Pro Leu Cys Gly Val Val His Ala Ala Gly Val Leu245024552460Ala Asp Gly Val Ile Glu Ser Leu Thr Pro Glu Asp Val Gly Ala246524702475Val Phe Gly Pro Lys Ala Ala Gly Ala Trp Asn Leu His Glu Leu248024852490Thr Arg Asp Met Asp Leu Ser Phe Phe Ala Leu Phe Ser Ser Leu249525002505Ser Gly Val Thr Gly Ala Ala Gly Gln Gly Asn Tyr Ala Ala Ala
251025152520Asn Thr Phe Leu Asp Ala Leu Ala His Tyr Arg Arg Ala Gln Gly252525302535Leu Pro Ala Val Ser Leu Ala Trp Gly Leu Trp Glu Gln Ser Ser254025452550Gly Met Thr Gly Arg Leu Ser Asp Val Asp Arg Ser Arg Ile Ala255525602565Arg Ser Ser Pro Pro Leu Ser Thr Lys Asp Gly Leu Arg Leu Phe257025752580Asp Ala Gly Leu Ala Leu Asp Arg Ala Ala Val Val Pro Ala Arg258525902595Leu Asp Arg Ala Phe Leu Ala Glu Gln Ala Arg Ser Gly Thr Leu260026052610Pro Ala Met Leu Thr Ala Leu Val Pro Thr Ile Thr Ser Ile Arg261526202625Arg Ser Ser Gly Thr Asp Leu Ala Asp Glu Asp Ala Leu Leu Gly263026352640Val Val Arg Glu His Ala Ala Arg Val Leu Gly Tyr Ser Gly Ala264526502655Ala Glu Val Gly Val Glu Arg Ala Phe Arg Asp Leu Gly Phe Asp266026652670Ser Leu Ser Gly Val Glu Leu Arg Asn Arg Leu Ala Gly Val Leu267526802685Gly Ala Arg Leu Pro Ala Thr Ala Val Phe Asp Tyr Pro Thr Pro269026952700Arg Ala Leu Ala Arg Phe Leu His Gln Glu Leu Ala Gly Glu Val270527102715Gly Thr Thr Pro Ala Pro Val Thr Thr Thr Thr Ala Ser Val Glu272027252730Asp Asp Leu Val Ala Ile Val Gly Met Gly Cys Arg Tyr Pro Gly273527402745Gly Val Ser Ser Pro Glu Glu Leu Trp Arg Leu Val Ala Gly Gly275027552760Val Asp Ala Val Ala Asp Phe Pro Asp Asp Arg Gly Trp Asp Leu276527702775Ala Gly Leu Phe Asp Pro Asp Pro Asp Arg Phe Gly Thr Ser Tyr278027852790Val Arg Glu Gly Gly Phe Leu Arg Asp Ala Ala Glu Phe Asp Ala279528002805Ala Phe Phe Gly Ile Ser Pro Arg Glu Ala Leu Ala Met Asp Pro
281028152820Gln Gln Arg Leu Leu Leu Glu Leu Ser Trp Glu Ala Val Glu Arg282528302835Ala Gly Ile Asp Pro Gly Ser Leu Arg Gly Ser Arg Thr Gly Val284028452850Phe Ala Gly Leu Met Tyr His Asp Tyr Ala Gly Arg Phe Ala Ala285528602865Gly Val Pro Glu Gly Phe Glu Gly Tyr Leu Gly Asn Gly Ser Ala287028752880Gly Ser Val Ala Ser Gly Arg Val Ala Tyr Ser Phe Gly Phe Glu288528902895Gly Pro Ala Val Thr Val Asp Thr Ala Cys Ser Ser Ser Leu Val290029052910Ala Leu His Leu Ala Gly Gln Ser Leu Arg Ser Gly Glu Cys Asp291529202925Leu Ala Leu Ala Gly Gly Val Thr Val Met Ala Thr Pro Ala Thr293029352940Phe Val Glu Phe Ser Arg Gln Arg Gly Leu Ala Pro Asp Gly Arg294529502955Cys Lys Ser Phe Ala Glu Ala Ala Asp Gly Thr Gly Trp Gly Glu296029652970Gly Ala Gly Leu Val Leu Leu Glu Arg Leu Ser Asp Ala Arg Arg297529802985Asn Gly His Arg Val Leu Ala Val Val Arg Gly Ser Ala Val Asn299029953000Gln Asp Gly Ala Ser Asn Gly Leu Thr Ala Pro Asn Gly Pro Ser300530103015Gln Gln Arg Val Ile Thr Gln Ala Leu Thr Ser Ala Gly Leu Ser302030253030Val Ser Asp Val Asp Ala Val Glu Ala His Gly Thr Gly Thr Arg303530403045Leu Gly Asp Pro Ile Glu Ala Gln Ala Leu Ile Ala Thr Tyr Gly305030553060Arg Asp Arg Asp Pro Asp Arg Pro Leu Trp Leu Gly Ser Met Lys306530703075Ser Asn Ile Gly His Thr Gln Ala Ala Ala Gly Val Ala Gly Val308030853090Ile Lys Met Val Met Ala Met Arg His Gly Glu Lsa Pro Arg Thr309531003105Leu His Val Gly Glu Pro Thr Ser Glu Val Asp Trp Ser Ala Gly
311031153120Ser Val Gln Leu Leu Thr Glu Asn Thr Pro Trp Pro Asp Ser Gly312531303135His Pro Arg Arg Ala Gly Val Ser Ser Phe Gly Ile Ser Gly Thr314031453150Asn Ala His Val Ile Leu Glu Gln Ser Pro Thr Ala Ser Ser Glu315531603165Phe Val Glu His Ser Gly Pro Asp Ser Glu Ser Ala Val Asn Val317031753180Pro Val Val Pro Trp Val Val Ser Gly Lys Thr Pro Glu Ala Leu318531903195Ser Ala Gln Ala Asp Thr Leu Val Ser Tyr Leu Asp Asp Arg Ser320032053210Asp Val Ser Ser Arg Asp Val Gly Tyr Ser Leu Ala Met Thr Arg321532203225Ser Ala Leu Asp Glu Arg Ala Val Val Leu Gly Ser Asp Arg Glu323032353240Thr Leu Leu Ser Gly Leu Lys Ala Leu Ala Ala Gly His Glu Ala324532503255Thr Gly Val Val Thr Gly Ser Val Gly Ser Gly Gly Arg Pro Gly326032653270Phe Val Phe Ala Gly Gln Gly Gly Gln Trp Leu Gly Met Gly Arg327532803285Gly Leu Tyr Arg Ala Phe Pro Val Phe Ala Asp Ala Phe Asp Glu329032953300Ala Cys Ala Gly Leu Asp Ala His Leu Gly Gln Lys Val Gly Val330533103315Arg Asp Val Val Phe Gly Ser Asp Ala Gln Leu Leu Asp Arg Thr332033253330Leu Trp Ala Gln Ser Gly Leu Phe Ala Leu Gln Val Gly Leu Leu333533403345Lys Leu Leu Gly Ser Trp Gly Val Arg Pro Val Val Val Leu Gly335033553360His Ser Val Gly Glu Leu Ala Ala Ala Phe Ala Ala Gly Val Leu336533703375Ser Met Ala Glu Ala Ala Arg Leu Val Ala Gly Arg Ala Arg Leu338033853390Met Gln Ala Leu Pro Ser Gly Gly Ala Met Leu Ala Val Ala Thr339534003405Ser Glu Thr Gln Val Glu Pro Leu Leu Asp Gly Val Arg Asp Arg
34l034153420Ile Asp Ile Ala Ala Ile Asn Ala Pro Glu Ser Ile Val Lau Ser342534303435Gly Asp Arg Glu Leu Leu Thr Glu Ala Ala Asp Gln Leu His Asp344034453450Gln Gly Cys Arg Thr Arg Trp Leu G1n Val Ser His Ala Phe His345534603465Ser Pro Gln Met Asp Pro Met Leu Asp Glu Phe Ala Asp Ile Ala347034753480Arg Thr Val Asp Phe Arg Gly Ser Glu Leu Pro Val Val Ser Thr348534903495Leu Thr Gly Ala Leu Asp Asp Ser Gly Leu Met Ala Thr Pro Glu350035053510Tyr Trp Val Arg Gln Val Arg Glu Pro Val Arg Phe Ala Asp Gly351535203525Val Arg Ala Leu Val Glu His Asp Val Ala Thr Val Val Glu Leu353035353540Gly Pro Asp Gly Ala Leu Ser Ala LeuIle Gln Glu Cys Ala Ala354535503555Glu Phe Asp Gln Ser Arg Arg Val Ala Ala Val Pro Ala Met Arg356035653570Arg Ser Gln Asp Glu Ala Gln Lys Val Met Thr Ala Leu Ala Gln357535803585Val His Val Arg Gly Gly Ala Val Asp Trp Arg Ser Val Phe Ala359035953600Gly Thr Gly Ser Lys Gln Val Glu Leu Pro Thr Tyr Ala Phe Gln360536103615Arg Gln Arg Tyr Trp Leu Asn Ala Val His Glu Ser Ser Ala Gly362036253630Asp Met Gly Arg Arg Ile Glu Thr Glu Phe Trp Ser Ala Val Glu363536403645His Glu Asp Val Thr Ser Leu Ala Asn Ile Leu Gly Ile Val Asp365036553660Asp Gly Ala Ala Val Asp Ser Leu Arg Asn Ala Leu Pro Val Leu366536703675Ala Gly Trp Gln Arg Thr Arg Asn Asp Glu Ser Ile Met Asp Arg368036853690Gln Cys Tyr Arg Ile Gly Trp Arg Gln Val Ala Gly Leu Pro Pro369537003705Arg Gly Thr Val Phe Gly Thr Trp Leu Val Phe Ala Pro His Gly
37l037l53720Trp Ser Gly Glu Pro Gln Val Ala Asn Cys Val Ala Ala Leu Arg372537303735Ala Ser Gly Ala Ser Val Val Ler Val Glu Ala Asp Pro Asp pro374037453750Val Val Phe Gly Asp Arg Val Arg Thr Leu Cys Ser Asp Ser Pro375537603765Asp Leu Val Gly Val Leu Ser Met Leu Cys Leu Glu Glu Ser Ala377037753780Ile Pro Gly Phe Ser Ala Val Ser Arg Gly Phe Ala Leu Thr Val378537903795Glu Leu Val Arg Ala Leu Ala Ala Ala Gly Ala Asp Ala Arg Leu3800380538l0Trp Leu Leu Thr Cys Gly Gly Val Ser Val Gly Asp Val Pro Val38l538203825Arg Pro Glu Gln Ala Leu Val Trp Gly Leu Gly Arg Val Ala Gly383038353840Leu Glu His Pro Asp Trp Trp Gly Gly Leu Ile Asp Ile Pro Val384538503855Leu Phe Asp Glu Asp Ala Gln Glu Arg Leu Ser Ile Val Leu Ala386038653870Gly Leu Gly Glu Glu Glu Val Ala Ile Arg Ser Asp Gly Val Phe387538803885Ala Arg Arg Leu Val Arg His Gly Val Ser Ala Gly Val Lys Lys389038953900Ala Trp Arg Pro Arg Gly Ser Val Leu Val Thr Gly Gly Thr Gly390539l039l5Gly Leu Gly Ala His Ala Ala Arg Trp Leu Ala Asp Ala Gly Ala392039253930Glu His Val Val Met Val Ser Arg Arg Gly Glu Gln Ala Pro Ser393539403945Ala Glu Lys Leu Arg Thr Glu Leu Glu Asp Leu Gly Thr Arg Val395039553960Ser Ile Leu Ser Cys Vap Val Thr Asp Arg Glu Ala Leu Ala Glu396539703975Val Leu Lys Ala Leu Pro Ala Glu Tyr Pro Leu Thr Ala Val Val398039853990His Thr Ala Gly Val Ile Glu Thr Gly Asp Ala Ala Ser Met Ser399540004005Leu Ala Asp Phe Asp Asp Val Leu Ser Ala Lys Val Ala Gly Ala
40l040l54020Ala Asn Leu Asp Ala Leu Leu Ala Asp Val Glu Leu Asp Ala Phe402540304035Val Leu Phe Ser Ser Val Ser Gly Val Trp Gly Ala Gly Gly Gln404040454050Gly Ala Tyr Ala Ala Ala Asn Ala Tyr Leu Asp Ala Leu Ala Glu405540604065Glu Arg Arg Ser Arg Gly Leu Val Ala Thr Ala Val Ala Trp Gly407040754080Pro Trp Ala Gly Glu Gly Met Ala Ala Gly Glu Thr Gly Asp Gln408540904095Leu Arg Arg Tyr Gly Leu Ser Pro Met Gly Pro Gln Tyr Ala Ile410041054110Ala Gly Ile Arg Arg Ala Val Glu Gln Asp GluIle Ser Leu Val411541204125Val Ala Asp Val Asp Trp Ala Arg Phe Ser Ala Gly Phe Leu Ala413041354140Ala Arg Pro Arg Pro LeuLeu Asn Glu Leu Thr Glu Val Lys Glu414541504155Leu Leu Val Asn Ala Gln Ser Glu Val Gly Val Val Ala Glu Ala416041654170Ser Val Ala Trp Arg Gln Arg Leu Ala Ala Ala Pro Arg Pro Ala417541804185Gln Glu Gln Leu Ile Leu Glu Leu Val Arg Gly Glu Thr Ala Leu419041954200Val Leu Gly His Pro Gly Ala Glu Ala Val Ala Pro Glu Arg Ala420542104215Phe Lys Asp Ser Gly Phe Asp Ser Gln Ala Ala Val Glu Leu Arg422042254230Val Arg Leu Asn Arg Ala Thr Gly Leu Gln Leu Pro Ser Thr Ile423542404245Ile Phe Ser His Pro Thr Pro Ala Glu Leu Ala Ala Glu Leu Arg425042554260Ala Arg Leu Leu Pro Glu Ser Ala Gly Val Asp Ile Ser Glu Glu426542704275Asp Glu Ala Arg Ile Arg Ala Ala Leu Thr Ser Ile Pro Phe Ala428042854290Ala Leu Arg Glu Ala Asp Leu Val Asn Arg Leu Leu Ala Leu Ala429543004305Gly His Pro Val Asp Ser Gly Ser Ser Pro Asp Asp Ala Val Ala
431043154320Thr Ser Ile Asp Ala Met Asp Val Ala Asp Leu Val Glu Ala Ala432543304335Leu Gly Glu Arg Glu Ser4340<210>4<211>2149<212>PRT<213>刺糖多胞菌NRRL30141<400>4Val Thr Thr Ser Tyr Glu Glu Val Val Glu Ala Leu Arg Ala Ser Leu1 5 10 15Lys Glu Asn Glu Arg Leu Arg Arg Gly Arg Asp Arg Phe Ala Ala Glu20 25 30Lys Gly Asp Pro Ile Ala Ile Val Ala Met Ser Cys Arg Tyr Pro Gly35 40 45Gln Val Ser Ser Pro Glu Asp Leu Trp Gln Leu Ala Ala Gly Gly Val50 55 60Asp Ala Ile Ser Glu Val Pro Gly Asp Arg Gly Trp Asp Leu Ala Gly65 70 75 80Val Phe Asp Pro Asp Ser Asp Arg Pro Gly Thr Ser Tyr Ala Cys Ala85 90 95Gly Gly Phe Leu Gln Gly Val Ser Glu Phe Asp Ala Gly Phe Phe Gly100 105 110Ile Ser Pro Arg Glu Ala Leu Ala Met Asp Pro Gln Gln Arg Leu Leu115 120 125Leu Glu Val Ala Trp Glu Val Phe Glu Arg Ala Gly Leu Glu Gln Arg130 135 140Ser Thr Arg Gly Ser Arg Val Gly Val Phe Val Gly Thr Asn Gly Gln145 150 155 160Asp Tyr Ala Ser Trp Leu Arg Thr Pro Pro Ser Glu Val Ala Gly His165 170 175Val Leu Thr Gly Gly Ala Ala Ala Ile Leu Ser Gly Arg Val Ala Tyr180 185 190Ser Phe Gly Phe Glu Gly Pro Ala Val Thr Val Asp Thr Ala Cys Ser195 200 205Ser Ser Leu Val Ala Leu His Leu Ala Gly Gln Ala Leu Arg Ala Gly210 215 220Glu Cys Asp Leu Ala Leu Ala Gly Gly Val Thr Val Met Ser Thr Pro225 230 235 240
Lys Ala Phe Leu Glu Phe Ser Arg Gln Arg Gly Leu Ala Ala Asp Gly245 250 255Arg Cys Lys Ser Phe Ala Ala Ala Ala Asp Gly Thr Gly Trp Gly Glu260 265 270Gly Ala Gly Leu Leu Leu Leu Glu Arg Leu Ser Asp Ala Arg Arg Asn275 280 285Gly His Arg Val Leu Ala Val Val Arg Gly Ser Ala Val Asn Gln Asp290 295 300Gly Ala Ser Asn Gly Leu Thr Ala Pro Asn Gly Ser Ser Gln Ala Arg305 310 315 320Val Ile Thr Gln Ala Leu Ala Ser Ala Gly Leu Ser Val Ser Asp Val325 330 335Asp Ala Val Glu Ala His Gly Thr Gly Thr Arg Leu Gly Asp Pro Ile340 345 350Glu Ala Gln Ala Leu Ile Ala Thr Tyr Gly Arg Asp Arg Asp Pro Ala355 360 365Arg Pro Leu Trp Leu Gly Ser Val Lys Ser Asn Ile Gly His Thr Gln370 375 380Ala Ala Ala Gly Val Ala Gly Val Ile Lys Met Val Met Ala Met Arg385 390 395 400His Gly Gln Leu Pro Arg Thr Leu His Val Asp Ala Pro Ser Pro Glu405 410 415Val Asp Trp Ser Ala Gly Thr Val Gln Leu Leu Thr Glu Asn Met Leu420 425 430Trp Pro Glu Ser Gly Arg Val Arg Arg Ala Gly Val Ser Ser Phe Gly435 440 445Ile Ser Gly Thr Asn Ala His Val Ile Leu Glu Gln Pro Thr Gly Glu450 455 460Thr Arg Gln Ser Ala Gly Pro Asp Ser Gly Ser Val Val Asp Val Pro465 470 475 480Val Val Pro Trp Met Val Ser Gly Lys Thr Pro Asp Ala Leu Gly Ala485 490 495Gln Ala Asp Thr Leu Met Ser Tyr Lau Asp Asp Arg Val Asp Val Pro500 505 510Ser Leu Asp Ile Ala Tyr Ser Leu Ala Met Thr Arg Ser Ala Leu Asp515 520 525Glu Arg Ala Val Val Lau Gly Pro Asp Arg Glu Thr Leu Leu Ser Gly530 535 540Leu Lys Ala Leu Ser Ala Gly His Glu Ala Ser Gly Val Val Thr Gly545 550 555 560
Ser Val Gly Thr Gly Gly Arg Ile Gly Phe Val Phe Ser Gly Gln Gly565 570 575Gly Gln Trp Leu Gly Met Gly Arg Gly Leu Tyr Arg Ala Phe Pro Val580 585 590Phe Ala Ala Ala Phe Asp Glu Ala Cys Ala Glu Leu Glu Ala His Leu595 600 605Gly Gln Glu Val Gly Val Arg Asp Val Val Phe Gly Ser Asp Ala Gln610 615 620Leu Leu Asn Arg Thr Leu Trp Ala Gln Ser Gly Leu Phe Ala Leu Gln625 630 635 640Val Gly Leu Leu Lys Leu Leu Asp Ser Trp Gly Val Arg Pro Ser Ala645 650 655Val Leu Gly His Ser Val Gly Glu Leu Ala Ala Ala Phe Ala Ala Gly660 665 670Val Leu Ser Leu Ser Asp Ala Ala Arg Leu Val Ala Gly Arg Ala Arg675 680 685Leu Met Gln Ala Leu Pro Ser Gly Gly Gly Met Leu Ala Val Ala Ala690 695 700Gly Glu Glu Gln Leu Arg Pro Leu Leu Ala Asp His Gly Asp Arg Val705 710 715 720Gly Leu Ala Ala Val Asn Val Ala Glu Ser Val Val Leu Ser Gly Asp725 730 735Arg Asp Val Leu Asp Asp Ile Ala Gly Arg Leu Asp Gly Gln Gly Val740 745 750Arg Thr Arg Trp Leu Arg Val Ser His Ala Phe His Ser Tyr Arg Met755 760 765Asp Pro Met Leu Asp Glu Phe Ala Glu Ile Ala Arg Ala Val Asp Tyr770 775 780Arg Arg Cys Glu Leu Pro Ile Val Ser Thr Leu Thr Gly Lys Leu Asp785 790 795 800Asp Ala Gly Arg Met Ser Gly Pro Asp Tyr Trp Val Arg Gln Val Arg805 810 815Glu Pro Val Arg Phe Ala Asp Gly Ala Gln Ala Leu Val Glu His Asp820 825 830Val Ala Thr Ile Val Glu Ile Gly Pro Asp Gly Ala Leu Ser Ala Leu835 840 845Ile Gln Glu Cys Val Ala Ala Ser Asp GAn Ser Arg Arg Val Ala Ala850 855 860Val Pro Ala Met Arg Arg Asn Arg Asp Glu Ala Gln Asn Leu Thr Thr865 870 875 880
Ala Leu Ala Gln Val His Val Arg Gly Gly Ala Val Asp Trp Arg Ser885 890 895Phe Phe Ala Gly Thr Gly Ala Lys Gln Val Glu Leu Pro Thr Tyr Ala900 905 910Phe Gln Arg Gln Arg Tyr Trp Leu Glu Pro Ser Asp Ser Gly Asp Val915 920 925Thr Gly Ala Gly Leu Ala Gly Ala Glu His Pro Leu Leu Gly Ala Val930 935 940Val Pro Val Ala Gly Gly Asp Glu Val Leu Leu Thr Gly Arg Ile Ser945 950 955 960Val Gly Thr His Pro Tro Leu Ala Glu His Arg Val Leu Gly Glu Val965 970 975Ile Val Pro Gly Thr Ala Leu Leu Glu Ile Ala Leu His Ala Gly Glu980 985 990Arg Leu Gly Cys Glu Arg Val Glu Glu Leu Thr Leu Glu Ala Pro Leu995 10001005Val Leu Pro Glu Arg Gly Ala Met Gln Val Gln Leu Arg Val Gly101010151020Ala Pro Glu Asn Ser Gly Arg Arg Pro Met Val Leu Tyr Ser Arg102510301035Pro Glu Gly Ala Ala Asp His Asp Trp Thr Arg His Ala Thr Gly104010451050Arg Leu Ala Pro Gly Gly Gly Glu Ala Ala Gly Asp Leu Ala Asp105510601065Trp Pro Ala Pro Gly Ala Leu Pro Val Asp Leu Asp Glu Phe Tyr107010751080Arg Asp Leu Ala Glu His Gly Leu Glu Tyr Gly Pro Ile Phe Gln108510901095Gly Leu Lys Ala Ala Trp Arg Gln Gly Asp Glu Val Tyr Ala Glu110011051110Ala Ala Leu Pro Gly Thr Glu Asp Ser Gly Phe Gly Val His Pro111511201125Ala Leu Leu Asp Ala Ala Leu His Ala Thr Ala Val Arg Asp Met113011351140Asp Gly Ala Trp Leu Pro Phe Gln Trp Glu Gly Val Cys Leu His114511501155Ala Arg Ala Ala Ser Ala Leu Arg Val Arg Val Val Pro Ala Gly116011651170Asp Asp Ala Lys Ser Leu Leu Val Cys Asp Gly Thr Gly Arg Pro117511801185
Val Ile Ser Val Agp Arg Leu Val Phe Arg Ser Ala Ala Ala Gly119011951200Arg Thr Gly Ala Arg Arg Gln Ala His Arg Ala Arg Leu Tyr Arg120512101215Leu Gly Trp Pro Thr Val Gln Leu Pro Thr Ser Ala Gln Pro Pro122012251230Ser Cys Val Leu Leu Gly Thr Ser Glu Val Ser Ser Asp Met Gln123512401245Val Tyr Pro Asp Leu Arg Ser Leu Thr Ala Ala Leu Asp Ala Gly125012551260Ala Glu Pro Pro Gly Val Val Ile Ala Pro Thr Pro Pro Gly Gly126512701275Gly Gln Thr Ala Asp Val Arg Glu Ser Thr Arg His Ala Leu Asp128012851290Leu Val Gln Gly Trp Leu Ala Asp Gln Arg Leu Asn Asp Ser Arg129513001305Leu Phe Leu Val Thr Arg Gly Ala Val Ala Val Glu Pro Gly Glu131013151320Pro Val Thr Asp Leu Ala Gln Ala Ala Leu Trp Gly Leu Leu Arg132513301335Ser Thr Gln Thr Glu His Pro Asp Arg Phe Val Leu Val Asp Val134013451350Ala Glu Pro Ala Gln Leu Leu Pro Ala Leu Pro Gly Val Leu Ala135513601365Cys Gly Glu Pro Gln Leu Ala Leu Arg Arg Gly Gly Ala His Ala137013751380Pro Arg Leu Ala Gly Leu Gly Gly Asp Asp Val Leu Pro Val Pro138513901395Asp Ser Met Gly Trp Arg Leu Glu Ala Thr Ser Pro Gly Thr Leu140014051410Asp Gly Leu Ala Leu Leu Asp Glu Pro Ala Ala Thr Ala Ser Leu141514201425Gly Asp Gly Gln Val Arg Ile Ala Met Arg Ala Ala Gly Val Asn143014351440Phe Arg Asp Ala Leu Ile Ala Leu Gly Met Tyr Pro Gly Ala Ala144514501455Ser Leu Gly Gly Glu Gly Ala Gly Val Val Val Glu Thr Gly Pro146014651470Gly Val Thr Gly Leu Ala Pro Gly Asp Arg Val Met Gly Met Ile147514801485
Pro Lys Ala Phe Gly Pro Leu Ala Val Ala Asp His Arg Met Val149014951500Thr Arg Ile Pro Ala Gly Trp Ser Phe Ala Gln Ala Ala Ser Val150515101515Pro Ile Val Phe Leu Thr Ala Tyr Tyr Ala Leu Val Asp Leu Ala15201525I530Gly Leu Arg Pro Gly Glu Ser Leu Leu Val His Ser Ala Ala Gly153515401545Gly Val Gly Met Ala Ala Ile Gln Leu Ala Arg His Leu Gly Ala155015551560Glu Val Tyr Ala Thr Ala Ser Glu Asp Lys Trp Gln Ala Val Glu156515701575Leu Thr Arg Glu Arg Leu Ala Ser Ser Arg Thr Cys Asp Phe Glu158015851590Lys Gln Phe Leu Gly Ala Thr Gly Gly Arg Gly Val Asp Val Val159516001605Leu Asn Ser Leu Ala Gly Asp Phe Ala Asp Ala Ser Leu Arg Met161016151620Leu Pro Arg Gly Gly Arg Phe Leu Glu Leu Gly Lys Thr Asp Val162516301635Arg Asp Pro Val Glu Val Ala Asp Ala His Pro Gly Val Ser Tyr164016451650Gln Ala Phe Asp Thr Val Glu Ala Gly Pro Gln Arg Ile Gly Glu165516601665Met Leu Asp Glu Leu Val Glu Leu Phe Glu Gly Gly Val Leu Glu167016751680Pro Leu Pro Val Thr Ala Trp Asp Val Arg Gln Ala Pro Glu Ala168516901695Leu Arg His Leu Ser Gln Ala Arg His Val Gly Lys Leu Val Leu170017051710Thr Met Pro Pro Ala Trp Asp Thr Ala Gly Thr Val Leu Val Thr171517201725Gly Gly Thr Gly Ala Leu Gly Ala Glu Val Ala Arg His Leu Val173017351740Ile Glu His Gly Val Arg Asn Leu Val Leu Val Ser Arg Arg Gly174517501755Pro Ala Ala Ser Gly Ala Ala Glu Leu Val Ala Gln Leu Thr Ala176017651770Tyr Gly Ala Glu Val Ser Leu Gln Ala Cys Asp Val Ala Asp Arg177517801785
Glu Thr Leu Ala Lys Val Leu Ala Gly Ile Pro Asp Glu His Thr179017951800Leu Thr Ala Val Val His Ala Ala Gly Val Leu Asp Asp Gly Val180518101815Ala Glu Ser Leu Thr Ala Gln Arg Leu Asp His Val Leu Arg Pro182018251830Lys Val Asp Gly Ala Arg Asn Leu His Glu Leu Ile Ala Pro Asp183518401845Val Ala Leu Val Leu Phe Ser Ser Val Ser Gly Val Leu Gly Ser185018551860Gly Gly Gln Gly Asn Tyr Ala Ala Ala Asn Ser Phe Leu Asp Ala186518701875Leu Ala Gln Gln Arg Gln Ser Arg Gly Leu Pro Thr Arg Ser Leu188018851890Ala Trp Gly Pro Trp Ala Glu His Gly Met Ala Ser Thr Leu Arg189519001905Glu Ala Glu Gln Asp Arg Leu Ala Leu Ser Gly Leu Leu Pro Ile191019151920Ser Thr Glu Glu Gly Leu Ser Gln Phe Asp Ala Ala Cys Gly Gly192519301935Ala His Thr Val Val Ala Pro Val Arg Ile Gly Arg Ser Ser Asp194019451950Gly Asn Pro Ile Lys Phe Pro Val Leu Arg Gly Leu Val Glu Pro195519601965His Arg Val Asn Lys Ala Thr Ala Asp Asp Ala Glu Ser Ile Arg197019751980Lys Arg Leu Gly Arg Leu Pro Asp Ala Glu Gln His Arg Ile Leu198519901995Leu Asp Leu Val Arg Thr His Val Ala Ala Val Leu Gly Phe Ala200020052010Gly Pro Gln Glu Ile Thr Ala Asp Gly Thr Phe Lys Ala Leu Gly201520202025Phe Asp Ser Leu Thr Val Val Glu Leu Arg Asn Arg Ile Asn Gly203020352040Ala Thr Gly Leu Arg Leu Pro Ala Thr Leu Val Phe Asn Tyr Pro204520502055Thr Pro Asp Ala Leu Ala Ala His Leu Val Thr Ala Leu Ser Ala206020652070Asp Arg Leu Ala Gly Thr Phe Glu Glu Leu Asp Arg Trp Ala Ala207520802085
Asn Leu Pro Ala Leu Ala Arg Asp Glu Ala Thr Arg Ala Gln Ile209020952100Thr Thr Arg Leu Gln Ala Ile Leu Gln Ser Leu Ala Asp Val Ser210521102115Gly Gly Thr Gly Gly Gly Ser Val Pro Asp Arg Leu Arg Ser Ala212021252130Thr Asp Glu Glu Leu Phe Gln Leu Leu Asp Asn Asp Leu Glu Leu213521402145Pro<210>5<211>3167<212>PRT<213>刺糖多胞菌NRRL30141<400>5Met Ser Asn Glu Glu Lys Leu Arg Glu Tyr Leu Arg Arg Ala Leu Val15 10 15Asp Leu His Gln Ala Arg Glu Arg Leu Asp Glu Ala Glu Ser Gly Glu20 25 30Gln Glu Pro Ile Ala Ile Val Ala Met Gly Cys Arg Tyr Pro Gly Gly35 40 45Val His Asp Pro Glu Gly Leu Trp Lys Leu Val Ala Ser Gly Gly Asp50 55 60Ala Ile Gly Glu Phe Pro Ala Asp Arg Gly Trp His Leu Asp Glu Leu65 70 75 80Tyr Asp Pro Asp Pro Asp Gln Pro Gly Thr Cys Tyr Thr Arg His Gly85 90 95Gly Phe Leu His Glu Ala Gly Glu Phe Asp Ala Gly Phe Phe Asp Ile100 105 110Ser Pro Arg Glu Ala Leu Ala Met Asp Pro Gln Gln Arg Leu Leu Leu115 120 125Glu Ile Ser Trp Glu Thr Val Glu Ser Ala Gly Met Asp Pro Arg Ser130 135 140Leu Arg Gly Ser Arg Thr Gly Val Phe Ala Gly Leu Met Tyr Glu Gly145 150 155 160Tyr Asp Thr Gly Ala His Pro Glu Gly Val Glu Gly Tyr Leu Gly Thr165 170 175Gly Asn Ala Gly Ser Val Ala Ser Gly Arg Val Ala Tyr Ser Phe Gly180 185 190Phe Glu Gly Pro Ala Val Thr Val Asp Thr Ala Cys Ser Ser Ser Leu
195 200 205Val Ala Leu His Leu Ala Cys Gln Ser Leu Arg Gln Gly Glu Cys Asp210 215 220Leu Ala Leu Ala Gly Gly Val Thr Val Met Ala Thr Pro Ala Thr Phe225 230 235 240Val Glu Phe Ser Arg Gln Arg Gly Leu Ala Pro Asp Gly Arg Cys Lys245 250 255Ser phe Ala Ala Ala Ala Asp Gly Thr Gly Trp Gly Glu Gly Ala Gly260 265 270Leu Val Leu Leu Glu Arg Leu Ser Asp Ala Arg Arg Asn Gly His Arg275 280 285Val Leu Ala Val Val Arg Gly Ser Ala Val Asn Gln Asp Gly Ala Ser290 295 300Asn Gly Leu Thr Ala Pro Asn Gly Leu Ala Gln Glu Arg Val Ile Gln305 310 315 320Gln Ala Leu Thr Ser Ala Gly Leu Ser Val Ser Asp Val Asp Val Val325 330 335Glu Ala His Gly Thr Gly Thr Arg Leu Gly Asp Pro Ile Glu Ala Gln340 345 350Ala Leu Ile Ala Thr Tyr Gly Gln Asp Arg Asp Arg Asp Arg Pro Leu355 360 365Trp Leu Gly Ser Val Lys Ser Asn Ile Gly His Thr Gln Ala Ala Ala370 375 380Gly Val Ala Gly Val Ile Lys Met Val Met Ala Met Arg Arg Gly Glu385 390 395 400Leu Pro Arg Thr Leu His Val Asp Glu Pro Asn Ser His Val Asp Trp405 410 415Ser Ala Gly Ala Val Arg Leu Leu Thr Glu Asn Ile Arg Trp Pro Gly420 425 430Thr Gly Thr Arg Arg Val Gly Val Ser Ser Phe Gly Val Ser Gly Thr435 440 445Asn Ala His Val Ile Leu Glu His Asp Pro Leu Ala Leu Thr Glu Asn450 455 460Glu Asn Ala Ala Val Ser Pro Ala Pro Gly Ile Val Pro Trp Ala Leu465 470 475 480Ser Gly Arg Ser Ser Thr Ala Leu Arg Ala Gln Ala Glu Arg Leu Ser485 490 495Glu Leu Cys Glu Gln Thr Asp Pro Asp Pro Val Asp Val Gly Phe Ser500 505 510Leu Ala Thr Thr Arg Thr Ala Trp Glu His Arg Ala Val Val Leu Gly
515 520 525Gly Asp Ser Ala Thr Leu Arg Ser Gly Leu Gly Val Val Ala Ser Gly530 535 540Glu Pro Ala Val Asp Val Val Gln Gly Ser Val Leu Gly Gly Glu Val545 550 555 560Val Phe Val Phe Pro Gly Gln Gly Trp Gln Trp Ala Gly Met Ala Val565 570 575Asp Leu Leu Asp Ala Ser Pro Thr Phe Ala Arg His Met Asp Glu Cys580 585 590Ala Thr Ala Leu Arg Lys Tyr Val Asp Trp Ser Leu Val Asp Val Leu595 600 605Arg Gly Ala Glu Asn Ala Pro Pro Leu Asp Arg Val Asp Val Leu Gln610 615 620Pro Val Ser Phe Ala Val Met Val Ser Leu Ala Glu Val Trp Arg Ser625 630 635 640Tyr Gly Val Arg Pro Ala Ala Val Val Gly His Ser Gln Gly Glu Ile645 650 655Ala Ala Ala Cys Ala Ala Gly Val Leu Pro Leu Glu Asp Ala Ala Arg660 665 670Leu Val Ala Leu Arg Ser Arg Ala Leu Lys Ala Leu Ser Gly Arg Gly675 680 685Gly Met Ala Ser Leu Ala Cys Ser Ala Asp Glu Ala Ala Ala Leu Phe690 695 700Ala Gly Leu Gly Gly Arg Leu Glu Ile Ala Ala Ile Asn Gly Pro Arg705 710715 720Ser Val Val Val Ser Gly Asp Leu Glu Ala Val Glu Glu Leu Leu Ala725 730 735Glu Cys Ala Glu Arg Asp Met Arg Ala Arg Arg Ile Pro Val Asp Tyr740 745 750Ala Ser His Ser Ala His Val Glu Val Val Arg Ser Pro Val Leu Ala755 760 765Ala Ala Ala Gly Val Arg His Arg Asp Gly Gln Val Pro Trp Trp Ser770 775 780Thr Val Ile Gly Asp Trp Leu Asp Pro Ala Gly Leu Asp Gly Glu Tyr785 790 795 800Trp Tyr Arg Asn Leu Arg Gln Pro Val Arg Phe Glu His Ala Val Gln805 810 815Gly Leu Val Glu Arg Gly Phe Gly Leu Phe Ile Glu Met Ser Ala His820 825 830Pro Val Leu Thr Met Ala Val Glu Glu Thr Ser Ala Glu Ser Glu Ser
835 840 845Ala Val Ala Ala Val Gly Thr Leu Arg Arg Asp Ser Gly Gly Arg Arg850 855 860Arg Leu Leu Gln Ser Leu Ala Glu Ala Tyr Val Arg Gly Ala Thr Val865 870 875 880Asp Trp Ala Val Ala Phe Gly Gly Val Gly Arg Arg Leu Asp Leu Pro885 890 895Thr Tyr Pro Phe Gln Arg Arg Arg Tyr Trp Leu Asp Arg Gly Ala Ala900 905 910Ser Glu Glu Ala Arg Ala Phe Ser Asp Pro Ala Ala Asp Trp Phe Trp915 920 925Gln Ala Val Glu Arg Gln Asp Leu Lys Gly Val Ala Asp Ala Leu Asp930 935 940Leu Asp Ala Asp Ala Pro Leu Ser Ala Thr Leu Pro Ala Leu Ser Val945 950 955 960Trp His Arg Gln Glu Arg Glu Lys Val Leu Val Asp Gly Trp Arg Tyr965 970 975Arg Val Asp Trp Val Pro Val Ala Pro Gln Pro Ile Arg Arg Thr Arg980 985 990Glu Thr Trp Leu Leu Val Val Pro Ala Gly Gly Ile Glu Glu Ala Leu995 10001005Val Glu Arg Leu Thr Asp Ala Leu Asn Thr Arg Gly Ile Ser Thr101010151020Leu Arg Leu Asp Val Pro Pro Thr Ala Thr Ser Gly Glu Leu Ala102510301035Thr Gly Leu Arg Ala Ala Val Gly Gly Asp Pro Val Lys Gly Ile104010451050Leu Ser Lau Thr Ala Leu Asp Glu Arg Thr His Pro Glu Arg Lys105510601065Ala Val Pro Ser Gly Ile Ala Leu Leu Leu Asn Leu Val Lys Ala107010751080Leu Gly Glu Gly Asp Leu Arg Val Pro Leu Trp Thr Ile Thr Arg108510901095Gly Ala Val Lys Ala Asp Pro Ala Asp Arg Leu Leu Arg Pro Met110011051110Gln Ala Gln Ala Trp Gly Leu Gly Arg Val Ala Ala Leu Glu His111511201125Pro Glu Arg Trp Gly Gly Leu Ile Asp Leu Pro Glu Ser Leu Asp113011351140Gly Asp Val Leu Thr Arg Leu Gly Glu Ala Leu Ile Asn Gly Leu
114511501155Ala Glu Asp Gln Leu Ala Ile Arg Gln Ser Gly Val Leu Ala Arg116011651170Arg Leu Val Pro Ala Pro Ala Asn Gln Pro Ala Gly Arg Lys Trp117511801185Arg Pro Arg Gly Ser Ala Leu Ile Thr Gly Gly Leu Gly Ala Val119011951200Gly Ala Gln Val Ala Arg Trp Leu Ala Glu Ser Gly Ala Glu Arg120512101215Ile Val Leu Thr Ser Arg Arg Gly Lys Glu Ala Pro Gly Ala Ala122012251230Glu Leu Glu Ala Glu Leu Arg Ala Leu Gly Ala Gln Val Ser Ile123512401245Val Ala Cys Asp Val Thr Asp Arg Ala Glu Met Ser Ala Leu Leu125012551260Ala Glu Phe Gly Val Thr Ala Val Phe His Ala Ala Gly Val Gly126512701275Arg Leu Leu Pro Leu Ala Glu Thr Glu Gln Asn Asp Leu Ala Glu128012851290Ile Cys Thr Ala Lys Val His Gly Ala Gln Val Leu Asp Glu Leu129513001305Cys Asp Ser Thr Asp Leu Asp Ala Phe Val Leu Phe Ser Ser Gly131013151320Ala Gly Val Trp Gly Gly Gly Gly Gln Gly Ala Tyr Gly Ala Ala132513301335Asn Ala Phe Leu Asp Thr Leu Ala Glu Gln Arg Arg Ala Arg Gly134013451350Leu Pro Ala Thr Ala Ile Ser Trp Gly Ser Trp Gly Gly Gly Met135513601365Ala Asp Gly Ala Ala Gly Glu Leu Leu Arg Arg Arg Gly Ile Arg137013751380Pro Met Pro Ala Ala Ser Ala Ile Leu Ala Leu Gln Glu Val Leu138513901395Asp Gln Asp Glu Thr Cys Val Ser Ile Ala Asp Val Asp Trp Asp140014051410Arg Phe Val Pro Thr Phe Ala Ala Thr Arg Ala Thr Arg Leu Leu141514201425Asp Glu Leu Pro Ala Val Arg Lys Ala Met Ser Ala Asn Gly Pro143014351440Ala Glu Pro Gly Gly Ser Pro Phe Ala Arg Asn Leu Ala Glu Leu
144514501455Pro Glu Ala Gln Arg Arg His Glu Leu Val Asp Leu Val Ser Ala146014651470Gln Val Ala Ala Val Leu Gly His Gly Ser Arg Glu Glu Val Gln147514801485Pro Glu Arg Ala Phe Arg Ala Leu Gly Phe Asp Ser Leu Met Ala149014951500Val Asp Leu Arg Asn Arg Leu Thr Thr Ala Thr Gly Leu Arg Leu150515101515Pro Thr Thr Thr Val Phe Asp Tyr Pro Asn Pro Ala Ala Leu Ala152015251530Ala His Leu Leu Glu Glu Leu Val Gly Asp Val Ala Ser Ala Ala153515401545Val Thr Thr Ala Ile Ala Pro Ser Thr Asp Glu Pro Val Ala Ile155015551560Val Ala Met Ser Cys Arg Phe Pro Gly Gly Ala His Ser Pro Glu156515701575Asp Leu Trp Arg Leu Val Ala Ser Gly Ala Glu Val Ile Gly Glu158015851590Phe Pro Ser Asp Arg Gly Trp Asp Ala Glu Ser Leu Tyr Asp Pro159516001605Asp Ala Ser Lys Pro Gly Thr Thr Tyr Ala Arg Met Ala Gly Phe161016151620Leu Tyr Asp Ala Gly Glu Phe Asp Ala Gly Leu Phe Gly Ile Ser162516301635Pro Arg Glu Ala Leu Ala Met Asp Pro Gln Gln Arg Leu Val Leu164016451650Glu Ile Ala Trp Glu Ala Leu Glu Arg Ala Gly Ile Asp Pro Leu165516601665Ser Leu Lys Gly Ser Gly Val Gly Thr Tyr Ile Gly Ala Gly Ser167016751680Arg Gly Tyr Ala Thr Asp Val Arg Gln Phe Pro Glu Glu Ala Glu168516901695Gly Tyr Leu Leu Thr Gly Thr Ser Ala Ser Val Leu Ser Gly Arg170017051710Val Ala Tyr Ser Phe Gly Phe Glu Gly Pro Ala Val Thr Val Asp171517201725Thr Ala Cys Ser Ser Ser Leu Val Ala Leu His Leu Ala Cys Gln173017351740Ser Leu Arg Ser Gly Glu Cys Asp Leu Ala Leu Ala Gly Gly Val
174517501755Thr Val Met Ser Thr Pro Glu Met Phe Val Glu Phe Ser Arg Gln176017651770Arg Gly Leu Ala Pro Asp Gly Arg Cys Lys Ser Phe Ala Glu Ser177517801785Ala Asp Gly Thr Gly Trp Gly Glu Gly Ala Gly Leu Leu Leu Leu179017951800Glu Arg Leu Ser Asp Ala His Arg Asn Gly His Arg Val Leu Ala180518101815Val Val Arg Gly Ser Ala Val Asn Gln Asp Gly Ala Ser Asn Gly182018251830Leu Ala Ala Pro Asn Gly Pro Ser Gln Gln Arg Val Ile Lys Gln183518401845Ala Leu Ala Asn Ala Gly Leu Ser Ala Ser Asp Val Asp Ala Val185018551860Glu Ala His Gly Thr Gly Thr Arg Leu Gly Asp Pro Ile Glu Ala186518701875Gln Ala Leu Ile Ala Thr Tyr Gly Gln Gly Arg Glu Arg Asp Arg188018851890Pro Leu Trp Leu Gly Ser Val Lys Ser Asn Ile Gly His Thr Gln189519001905Ala Ala Ala Gly Val Ala Gly Val Ile Lys Met Val Met Ser Met191019151920Arg Asn Asp Glu Leu Pro Ala Thr Leu His Val Gly Ala Pro Thr192519301935Ser Gln Val Asp Trp Ser Ala Gly Ala Val Arg Leu Leu Thr Glu194019451950Gln Val Pro Trp Pro Glu Ser Asp Arg Val Arg Arg Val Gly Val195519601965Ser Ser Phe Gly Ile Ser Gly Thr Ash Ala His Val Ile Leu Glu197019751980Gln Ser Thr Asn Ala Pro Asp Ser Pro Ala Ala Thr Asp Lys Ser198519901995Gly Ser Gly Ser Thr Val Asp Ile Pro Val Val Pro Trp Leu Val200020052010Ser Gly Gln Thr Ser Asp Ser Leu Arg Gly Gln Ala Glu Arg Val201520202025Leu Ser Gln Val Glu Ser Arg Pro Glu Gln Arg Pro Leu Asp Val203020352040Ala Tyr Ser Leu Ala Ser Gly Arg Ala Ala Leu Asp Glu Arg Ala
204520502055Val Val Leu Gly Ala Asp Arg Asn Glu Leu Val Ala Gly Leu Val206020652070Ala Leu Ala Ala Gly His Glu Ala Ser Gly Val Ile Thr Gly Thr207520802085Arg Ala Ser Ala Arg Phe Gly Phe Val Phe Ser Gly Gln Gly Gly209020952100Gln Trp Leu Gly Met Gly Arg Glu Leu Tyr Ser Lys Phe Pro Val210521102115Phe Ala Ala Ala Phe Asp Glu Ala Cys Ala Glu Leu Asp Ala His212021252130Leu Ser Glu Asp Leu Arg Val Arg Asp Val Val Phe Gly Ser Asp213521402145Ala Gln Leu Leu Asp Gln Thr Leu Trp Ala Gln Ser Gly Leu Phe215021552160Ala Leu Gln Val Gly Leu Leu Gly Leu Leu Gly Ser Trp Gly Val216521702175Arg Pro Asp Val Val Met Gly His Ser Val Gly Glu Leu Ala Ala218021852190Ala Phe Ala Ala Gly Val Leu Ser Leu Arg Asp Ala Ala Arg Leu219522002205Val Ala Ala Arg Ala Arg Leu Met Gln Ala Leu Pro Ser Asp Gly221022152220Ala Met Lau Ala Val Ala Ala Gly Glu Asp Leu Ile Arg Pro Leu222522302235Leu Ala Gly Arg Glu Ala Ser Val Asn Val Ala Ala Leu Asn Ala224022452250Pro Gly Ser Val Val Leu Ser Gly Asp Arg Asp Val Leu Ala Asp225522602265Ile Ala Gly Arg Leu Asn Glu Leu Gly Val Arg Thr Arg Arg Leu227022752280Arg Val Ser His Ala Phe His Ser His Arg Met Asp Pro Met Leu228522902295Gly Glu Phe Ala Gln Ile Ala Glu Ser Ala Glu Phe Gly Arg Pro230023052310Thr Thr Pro Leu Val Ser Thr Leu Thr Gly Glu Leu Asp Arg Ala231523202325Gly Glu Met Ser Thr Pro Gly Tyr Trp Val Arg Gln Val Arg Glu233023352340Pro Val Arg Phe Ala Asp Gly Val Arg Ala Leu Ala Ala Gln Gly
234523502355Val Asp Thr Val Val Glu Leu Gly Pro Asp Gly Ala Leu Ser Ala236023652370Leu Val Gln Glu Cys Ala Thr Gly Phe Asp Arg Val Gly Arg Ile237523802385Ser Pro Val Pro Leu Met Arg Arg Glu Arg Asp Glu Thr Arg Ser239023952400Val Met Thr Ala Leu Ala His Leu His Thr Arg Gly Gly Glu Leu240524102415Asp Trp Gln Ala Phe Phe Ser Gly Thr Gly Ala Arg Gln Val Glu242024252430Leu Pro Thr Tyr Ala Phe Gln Arg Arg His Tyr Trp Ile Glu Ser243524402445Ser Ala Arg Thr Ala Arg Asp Arg Ala Asp Ile Gly Glu Val Ala245024552460Glu Gln Phe Trp Thr Ala Val Glu Gln Gly Asp Leu Glu Ala Leu246524702475Val Ser Ala Leu Glu Leu Gly Ala Asp Asp Asp Thr Cyg Ala Ser248024852490Leu Ser Asp Val Leu Pro Ala Leu Ser Ser Trp Arg Ser Gly Leu249525002505Arg Asn Arg Ser Leu Val Asp Ser Cys Arg Tyr Arg Ile Asn Trp251025152520His Ser Ser Arg Glu Ala Pro Ala pro Lys Ile Ser Gly Thr Trp252525302535Leu Leu Val Val Pro Gly Asp Ala Asp Asp Gly Leu Ala Thr Ala254025452550Leu Thr Ser Ser Leu Val Glu Gly Gly Ala Glu Val Val Arg Ile255525602565Asp Leu Ser Glu Glu Asp Leu His Arg Glu Asp Leu Ala Gln Arg257025752580Leu Ala Asn Ala Leu Thr Asp Val Gly Arg Leu Gly Gly Val Leu258525902595Ser Leu Leu Gly Leu Asp Asp Ser Ala Val Gly Glu Phe Ser Cys260026052610Leu Thr Arg Gly Phe Ala Leu Thr Val Gln Leu Val Arg Ala Leu261526202625Arg Asn Ala Glu Leu Glu Ala Pro Leu Trp Ala Val Thr Arg Gly263026352640Gly Val Ser Leu Glu Asp Val Ser Val Ser Pro Glu Gln Ala Leu
264526502655Ile Trp Gly Leu Leu Arg Val Ala Gly Leu Glu His Pro Glu Phe266026652670Trp Gly Gly Leu Ile Asp Leu Pro Ser Asp Trp Asp Asp Arg Leu267526802685Gly Ala Arg Leu Val Gly Val Leu Ala Asp Gly Gly Glu Asp Gln269026952700Val Ala Ile Arg Arg Gly Gly Val Phe Val Arg Arg Leu Glu Arg270527102715Ala Gly Ala Ser Gly Ala Gly Ser Val Trp Arg Pro Arg Gly Thr272027252730Val Leu Val Thr Gly Gly Thr Gly Gly Leu Gly Ala His Val Ala273527402745Arg Trp Leu Ala Gly Ala Gly Ala Glu His Val Val Leu Thr Ser275027552760Arg Arg Gly Ala Glu Ala Pro Gly Ala Gly Glu Leu Arg Ala Glu276527702775Leu Glu Ala Leu Gly Ala Arg Val Ser Ile Val Pro Cys Asp Val278027852790Ala Asp Arg Asp Ala Val Ala Gly Val Leu Ala Gly Ile Gly Gly279528002805Glu Cys Pro Leu Thr Ala Val Val His Ala Ala Gly Val Gly Glu281028152820Ala Gly Gly Val Val Glu Met Ala Leu Ala Asp Phe Ala Glu Val282528302835Leu Ser Ala Lys Val Arg Gly Ala Ala Asn Leu Asp Glu Lau Leu284028452850Ala Asp Ser Glu Leu Asp Ala Phe Val Leu Phe Ser Ser Val Ser285528602865Gly Val Trp Gly Ala Gly Gly Gln Gly Ala Tyr Ala Ala Ala Asn287028752880Ala Tyr Leu Asp Ala Leu Ala Glu Gln Arg Arg Ala Ser Gly Leu288528902895Ala Gly Thr Ala Val Ala Trp Gly Pro Trp Ala Gly Asp Gly Met290029052910Ala Ala Gly Glu Thr Gly Ala Gln Leu His Arg Met Gly Leu Val291529202925Ser Met Glu Pro Arg Ala Ala Leu Leu Ala Leu Gln Gly Ala Leu293029352940Asp Arg Asp Glu Thr Ser Leu Val Val Ala Asp Val Asp Trp Ala
294529502955Arg phe Ala Pro Ala Phe Thr Ser Ala Arg Arg Arg Pro Leu Leu296029652970Asp Thr Ile Asp Glu Ala Arg Ala Ala Leu Glu Thr Thr Ser Glu297529802985Lys Ala Gly Thr Gly Lys Pro Val Glu Leu Lys His Arg Leu Ala299029953000Gly Leu Ser Arg Lys Glu Arg Asp Asp Ala Val Leu Asp Leu Val300530103015Arg Ala Glu Thr Ala Ala Val Leu Gly Arg Asp Asp Ala Thr Ala302030253030Leu Ala Pro Ser Arg Pro Phe Gln Glu Leu Gly Phe Asp Ser Leu303530403045Met Ala Val Glu Leu Arg Asn Arg Leu Asn Thr Ala Thr Gly Ile305030553060Gln Lau Pro Ala Ser Thr Ile Phe Asp Tyr Pro Asn Ala Glu Ser306530703075Leu Ser Arg His Leu Cys Ala Gly Leu Phe Pro Thr Glu Thr Thr308030853090Val Asp Ser Ala Leu Ala Glu Leu Asp Arg Ile Glu Gln Gln Leu309531003105Ser Met Phe Thr Glu Glu Ala Arg Ala Arg Asp Arg Ile Ala Thr311031153120Arg Leu Arg Ala Leu His Ala Lys Trp Asn Ser Ala Ser Glu Ala312531303135Pro Thr Gly Ala Asp Val Leu Asn Thr Leu Asp Ser Ala Thr His314031453150Asp Glu Ile Phe Glu Phe Ile Asp Asn Glu Leu Asp Leu Ser315531603165<210>6<211>4933<212>PRT<213>刺糖多胞菌NRRL30141<400>6Val Glu Ile Thr Met Ala Asn Glu Glu Lys Leu Phe Gly Tyr Leu Lys1 5 10 15Lys Val Thr Ala Asp Leu His Gln Thr Arg Gln Arg Leu Leu Ala Ala20 25 30Glu Ser Arg Ser Gln Glu Pro Ile Val Ser Ala Ser Cys Arg Leu Pro35 40 45
Gly Gly Val Asp Ser Pro Glu Ala Leu Trp Gln Leu Val Arg Thr Gly50 55 60Thr Asp Ala Ile Ser Glu Phe Pro Ala Asp Arg Gly Trp Asp Leu Asp65 70 75 80Arg Leu Tyr Asp Pro Asp Pro Asp His Gln Gly Thr Ser Tyr Thr Arg85 90 95Ala Gly Gly Phe Leu Ala Asp Ala Gly Asp Phe Asp Pro Ala Met Phe100 105 110Gly Ile Ser pro Arg Glu Ala Leu Ala Met Asp Pro Gln Gln Arg Leu115 120 125Leu Leu Glu Leu Thr Trp Glu Ala Leu Glu Arg Ala Gly Ile Asp Pro130 135 140Thr Ser Leu Arg Gly Ser Lys Thr Gly Val Phe Gly Gly Val Thr Pro145 150 155 160Gln Glu Tyr Gly Pro Pro Leu Pro Glu Met Ser Arg Asn Ser Gly Gly165 170 175Phe Gly Leu Thr Gly Arg Met Val Ser Val Ala Ser Gly Arg Val Ala180 185 190Tyr Ser Phe Gly Phe Glu Gly Pro Ala Val Thr Val Asp Thr Ala Cys195 200 205Ser Ser Ser Leu Val Ala Leu His Leu Ala Cys Gln Ser Leu Arg Ser210 215 220Gly Glu Cys Asp Leu Ala Leu Ala Gly Gly Val Thr Val Met Ala Thr225 230 235 240Pro Ala Thr Phe Val Glu Phe Ser Arg Gln Arg Gly Leu Ala Pro Asp245 250 255Gly Arg Cys Lys Ser Phe Ala Ala Ala Ala Asp Gly Thr Gly Trp Gly260 265 270Glu Gly Ala Gly Leu Val Leu Leu Glu Arg Leu Ser Asp Ala Arg Arg275 280 285Asn Gly His Lys Val Leu Ala Val Val Arg Gly Ser Ala Val Asn Gln290 295 300Asp Gly Ala Ser Asn Gly Leu Thr Ala Pro Asn Gly Pro Ser Gln Gln305 310 315 320Arg Val Ile Thr Gln Ala Leu Ser Asn Ala Gly Leu Ser Val Ser Asp325 330 335Val Asp Ala Val Glu Ala His Gly Thr Gly Thr Arg Leu Gly Asp Pro340 345 350Ile Glu Ala Gln Ala Leu Ile Ala Thr Tyr Gly Gln Gly Arg Glu Lys355 360 365
Asp Arg Pro Leu Trp Leu Gly Ser Val Lys Ser Asn Ile Gly His Thr370 375 380Gln Ala Ala Ala Gly Val Ala Gly Val Ile Lys Met Val Leu Ala Met385 390 395 400Arg His Gly Gln Leu Pro Ala Thr Leu His Val Asp Asp Pro Thr Ser405 4l0 4l5Ala Val Asp Trp Ser Ala Gly Ser Val Arg Leu Leu Thr Glu Asr Thr420 425 430Pro Trp Pro Asp Ser Gly Arg Pro Cys Arg Val Gly Val Ser Ser Phe435 440 445Gly Ile Ser Gly Thr Asn Ala His Val Ile Leu Glu Gln Ser Pro Val450 455 460Glu Gln Gly Glu Pro Thr Gly Pro Val Glu Gly Glu Arg Glu Pro Glu465 470 475 480Ala Ala Ile Pro Val Val Pro Trp Met Val Ser Gly Lys Thr Pro Glu485 490 495Ala Ala Arg Ala Gln Ala Glu Arg Val Leu Ser His Ile Glu Asp Arg500 505 510Pro Glu Leu Ser Pro Val Asp Val Ala Tyr Ser Leu Gly Met Thr Arg515 520 525Ala Ala Leu Asp Glu Arg Ala Val Met Leu Gly Ser Asp Arg Asp Thr530 535 540Leu Leu Thr Gly Leu Arg Ala Phe Ala Asp Gly Cys Asp Val Pro Glu545 550 555 560Val Val Ser Gly Ser Val Gly Asn Gly Gly Arg Val Gly Phe Val Phe565 570 575Ala Gly Gln Gly Gly Gln Trp Pro Gly Met Gly Arg Gly Leu Tyr Ser580 585 590Val Phe Pro Gly Phe Ala Asp Ala Phe Asp Glu Ala Cys Ala Glu Leu595 600 605Asp Thr His Leu Gly Gln Glu Leu Gly Val Arg Asp Val Val Phe Gly610 615 620Ser Asp Ala Arg Leu Val Asp Arg Thr Val Trp Ala Gln Ser Gly Leu625 630 635 640Phe Ala Leu Gln Val Gly Leu Leu Arg Leu Leu Gly Ser Trp Gly Val645650 655Arg Pro Asp Val Val Leu Gly His Ser Val Gly Glu Leu Ala Ala Val660 665 670His Ala Ala Gly Val Leu Ser Leu Pro Glu Ala Ala Arg Leu Val Ala675 680 685
Gly Arg Ala Arg Leu Met Gln Ala Leu Pro Ser Gly Gly Ala Met Leu690 695 700Ala Val Ala Ala Ser Glu Ala Gln Val Glu Pro Leu Leu Asp Arg Val705 710 715 720Arg Gly Arg Val Glu Ile Ala Ala Ile Asn Gly Pro Gly Ser Val Val725 730 735Leu Ser Gly Asp Arg Glu Leu Leu Thr Glu Ile Ala Asp Arg Leu His740 745 750Asp Gln Gly Cys Arg Thr Arg Trp Leu Arg Val Ser His Ala Phe His755 760 765Ser Pro His Met Glu Pro Met Leu Glu Glu Phe Ala Gln Ile Ala Arg770 775 780Ser Arg Glu Tyr Gln Ala Pro Glu Leu Pro Ile Ile Ser Thr Leu Thr785 790 795 800Gly Glu Leu Asp Gly Gly Arg Val Met Gly Thr Pro Glu Tyr Trp Val805 810 815Arg Gln Val Arg Glu Pro Val Arg Phe Ala Glu Gly Val Gln Ala Leu820 825 830Val Gly Gln Gly Ala Asp Thr Ile Val Glu Phe Gly Pro Asp Gly Ala835 840 845Leu Ser Thr Leu Val Glu Glu Cys Leu Ala Glu Ser Gly Arg Val Ala850 855 860Gly Ile Pro Leu Met Arg Lys Asp Arg Asp Glu Ala Arg Thr Val Leu865 870 875 880Ala Ala Leu Ala Gln Ile His Thr Arg Gly Gly Glu Val Glu Trp Gln885 890 895Ser Phe Phe Ala Gly Thr Gly Ala Lys Gln Val Glu Leu Pro Thr Tyr900 905 910Ala Phe Gln Arg Gln Arg Tyr Trp Leu Ala Ser Thr Gly Gly Ala Gly915 920 925Asp Val Thr Ala Ala Gly Leu Ala Glu Ala Asp His Pro Leu Leu Gly930 935 940Ala Val Val Ala Leu Ala Asp Gly Glu Gly Val Val Leu Thr Gly Arg945 950 955 960Leu Thr Ala Asp Ser His Pro Trp Leu Ser Asp His Arg Val Leu Gly965 970 975Glu Ile Val Val Pro Gly Thr Ala Ile Val Glu Leu Ala Trp His Val980 985 990Gly Glu Arg Leu Gly Cys Gly Arg Val Glu Glu Leu Ala Leu Glu Ala995 10001005
Pro Leu Ile Leu Pro Asp His Gly Ala Val Gln Val Gln Val Leu101010151020Val Gly Pro Pro Gly Glu Ser Gly Ala Arg Ser Val Ala Leu Tyr102510301035Ser Arg Pro Gly Asp Ala Thr Glu Ser Glu Trp Lys Lys His AIa104010451050Thr Gly Val Leu Leu Pro Pro Val Ala Ala Glu Asn His Glu Leu105510601065Pro Ala Trp Pro Pro Glu Asn Ala Thr Glu Ile Asp Ala Asp Glu107010751080Val Tyr Glu Phe Leu Glu Gly His Gly Phe Ala Tyr Gly Pro Ala108510901095Phe Arg Cys Leu Arg Gly Ala Trp Arg Arg Gly Gly Glu Val Phe110011051110Ala Glu Val Ala Leu Pro Asp Gly Met Gln Val Gly Val Asp Arg111511201125Phe Gly Val His Pro Ala Leu Leu Asp Ala Val Leu His Ala Ala113011351140Ala Ala Glu Thr Ser Val Val Gln Ser Glu Ala Arg Val Pro Phe114511501155Ser TIp Arg Gly Val Glu Leu Arg Ala Thr Glu Thr Ala Val Val116011651170Arg Ala Arg Ile Ser Leu Thr Ala Asp Asp Glu Leu Ser Leu Val117511801185Ala Val Asp Pro Val Gly Gly Phe Val Ala Ser Val Asp Ser Leu119011951200Val Thr Arg Pro Ile Ser Arg Gln Gln Val Arg Ser Gly A1a Ile120512101215Gly Asp Cys Leu Phe Glu Val Glu Trp His Arg Arg Ala Leu Leu122012251230Glu Thr Ala Ala Asp Asp Gly Leu Ala Ile Val Gly Asp Gly Ala123512401245Ser Trp Pro Glu Ser Val Arg Ala Thr Ala Arg Phe Ala Thr Leu125012551260Asp Glu Leu Arg Ser Ala Ala Asp Ser Asp Val Pro Ala Pro Gly126512701275Pro Val Leu Val Ala Ala Met Ser Ala Glu Glu Val Glu Ser Glu128012851290Ser Leu Pro Ser Arg Ala Gln Glu Ser Thr Ser Asp Leu Leu Ala129513001305
Leu Val Gln Ser Trp Leu Ala Asp Glu Gln Phe Ala Glu Ser Gln131013151320Leu Val Val Val Thr Arg Ala Ala Val Ser Ala Asp Ser Asp Thr132513301335Asp Val Ala Asp Leu Val Ser Ala Ser Ser Trp Gly Leu Leu Arg134013451350Ser Ala Gln Ser Glu Asn Pro Gly Arg Phe Val Leu Val Asp Val135513601365Asp Gly Thr Pro Glu Ser Trp Gln Ala Leu Pro Thr Ala Val Arg137013751380Ala Gly Glu Pro Gln Leu Ala Leu Arg Arg Gly Val Ala Leu Val138513901395Pro Arg Leu Ala Arg Leu Lys Ala His Gly Glu Gly Ser Ser Pro140014051410Arg Leu Asp Thr Asp Gly Thr Val Leu Ile Thr Gly Gly Thr Gly141514201425Ala Leu Gly Gly Val Val Ala Arg His Leu Val Ala Glu His Gly143014351440Ile Arg Arg Leu Val Leu Ala Gly Arg Arg Gly Trp Asn Ala Pro144514501455Gly Val His Asp Leu Val Asp Glu Leu Ala Arg Ser Gly Ala Val146014651470Val Asp Val Val Ala Cys Asp Val Gly Asn Arg Thr Asp Leu Glu147514801485Gln Ala Leu Ala Ala Ile Pro Val Asp Arg Pro Leu Arg Gly Ile149014951500Val His Thr Ala Gly Val Leu Ala Asp Gly Val Leu Gly Ser Leu150515101515Ser Ala Ala Asp Val Asp Thr Val Phe Ala Pro Lys Val Ala Gly152015251530Ala Trp His Leu His Glu Leu Thr Arg Glu Leu Asp Leu Ser Phe153515401545Phe Val Leu Phe Ser Ser Phe Ser Gly Ile Ala Gly Ala Ala Gly155015551560Gln Ala Asn Tyr Ala Ala Ala Asn Thr Phe Leu Asp Ala Leu Ala156515701575Gly Tyr Arg Arg Ala Arg Gly Leu Pro Gly Leu Ser Leu Ala Trp158015851590Gly Lau Trp Ala Gln Pro Gly Gly Met Thr Ser Gly Leu Asp Ala159516001605
Ala Ser Val Glu Arg Leu Ala Arg Thr Gly Ile Ala Glu His Ser161016151620Thr Glu Asp Gly Leu Arg Leu Phe Asp Ala Ala Ile Ala Lys Asp162516301635Arg Ala Cys Val Val Pro Ala Arg Leu Asp Arg Ala Leu Leu Val164016451650Glu His Ala Arg Ser His Ala Ile Pro Ala Leu Met Thr Ala Leu165516601665Ala Pro Ala Arg Gly Gly Val Ala Arg Arg Ala Thr Asn Ser Gln167016751680Ala Ala Asp Glu Asp Ala Leu Leu Gly Leu Val Arg Asp His Val168516901695Ser Ala Val Leu Gly Tyr Ser Gly Ala Val Glu Val Gly Gly Asp170017051710Arg Ala Phe Arg Asp Leu Gly Phe Asp Ser Leu Ser Gly Val Glu171517201725Leu Arg Asn Arg Leu Ala Gly Val Leu Gly Val Arg Leu Pro Ala173017351740Thr Ala Val Phe Asp Tyr Pro Thr Pro Arg Ala Leu Ala Arg Phe174517501755Leu His Gln Glu Leu Ala Gly Glu Val Gly Ser Met Ser Thr Pro176017651770Val Thr Arg Ala Ala Ser Val Glu Glu Asp Leu Ile Ala Ile Val177517801785Gly Met Gly Cys Arg Phe Pro Gly Gly Val Ser Ser Pro Glu Glu179017951800Leu Trp Arg Leu Val Ala Gly Gly Val Asp Ala Val Ala Gly Phe180518101815Pro Asp Asp Arg Gly Trp Asp Leu Ala Gly Leu Phe Asp Pro Asp182018251830Pro Asp His Leu Gly Thr Ser Tyr Val Cys Glu Gly Gly Phe Leu183518401845Arg Asp Ala Ala Glu Phe Asp Ala Asp Met Phe Gly Val Ser Pro185018551860Arg Glu Ala Leu Ala Met Asp Pro Gln Gln Arg Leu Leu Leu Glu186518701875Val Ala Trp Glu Thr Leu Glu Arg Ala Gly Ile Asp Pro Phe Ser188018851890Leu His Gly Ser Arg Thr Gly Val Phe Ala Gly Leu Met Tyr His189519001905
Asp Tyr Gly Ala Arg Phe Ile Thr Arg Ala Pro Glu Gly Phe Glu191019151920Gly His Leu Gly Thr Gly Asn Ala Gly Ser Val Leu Ser Gly Arg192519301935Val Ala Tyr Ser Phe Gly Phe Glu Gly Pro Ala Val Thr Val Asp194019451950Thr Ala Cys Ser Ser Ser Leu Val Ala Leu His Leu Ala Gly Gln195519601965Ala Leu Arg Ala Gly Glu Cys Glu Leu Ala Leu Ala Gly Gly Val197019751980Thr Val Met Ser Thr Pro Thr Thr Phe Val Glu Phe Ser Arg Gln198519901995Arg Gly Leu Ala Pro Asp Gly Arg Cys Lys Ser Phe Ala Ala Ala200020052010Ala Asp Gly Thr Gly Trp Gly Glu Gly Ala Gly Leu Val Leu Leu201520202025Glu Arg Leu Ser Asp Ala Arg Arg Asn Gly His Lys Val Leu Ala203020352040Val Val Arg Gly Ser Ala Val Asn Gln Asp Gly Ala Ser Asn Gly204520502055Leu Thr Ala Pro Asn Gly Pro Ser Gln Gln Arg Val Ile Thr Gln206020652070Ala Leu Thr Ser Ala Gly Leu Ser Leu Ser Asp Val Asp Ala Val207520802085Glu Ala His Gly Thr Gly Thr Arg Leu Gly Asp Pro Ile Glu Ala209020952100Gln Ala Leu Ile Ala Thr Tyr Gly Arg Asp Arg Asp Pro Gly Arg210521102115Pro Leu Trp Leu Gly Ser Val Lys Ser Asn Ile Gly His Thr Gln212021252130Ala Ala Ala Gly Val Ala Gly Val Ile Lys Met Val Met Ala Met213521402145Arg His Gly Glu Leu Pro Arg Thr Leu His Val Asp Glu Pro Ser215021552160Ala Gln Val Asp Trp Ser Ala Gly Thr Val Gln Leu Leu Thr Glu216521702175Asn Thr Pro Trp Pro Asp Ssr Gly Arg Leu Arg Arg Ala Gly Val218021852190Ser Ser Phe Gly Ile Ser Gly Thr Asn Ala His Leu Ile Leu Glu219522002205
Gln Pro Pro Arg Glu Thr His Arg Ala Thr Glu Pro Asp Ser Ser221022152220Ser Val Leu Asp Val Pro Val Val Pro Trp Met Val Ser Gly Lys222522302235Thr Pro Glu Ala Leu Ser Ala Gln Ala Asp Ala Leu Met Ser Tyr224022452250Leu Asn Asn Arg Val Asp Val Ser Pro Arg Asp Ile Gly Tyr Ser225522602265Leu Ala Val Thr Arg Pro Ala Leu Asp His Arg Ala Val Val Leu227022752280Gly Ala Asp Arg Glu Ala Leu Leu Pro Gly Leu Lys Ala Leu Ala228522902295Ala Ser His Asp Ala Ala Glu Val Ile Thr Gly Thr Arg Ala Ala230023052310Gly Pro Val Gly Phe Val Phe Ser Gly Gln Gly Gly Gln Trp Pro231523202325Gly Met Gly Ser Gly Leu Tyr Ser Ala Phe Pro Val Phe Ala Asp233023352340Ala Phe Asp Glu Ala Cys Gly Glu Leu Asp Ala His Leu Gly Gln234523502355Lys Ala Arg Val Arg Asp Val Met Ser Gly Ser Asp Lys Gln Leu236023652370Lau Asp Gln Thr Leu Trp Ala Gln Ser Gly Leu Phe Ala Leu Gln237523802385Val Gly Leu Trp Glu Leu Leu Gly Ser Trp Gly Val Arg Pro Gly239023952400Val Val Leu Gly His Ser Val Gly Glu Leu Ala Ala Ala Phe Ala240524102415Ala Gly Val Leu Ala Leu Pro Asp Ala Ala Arg Leu Val Ala Gly242024252430Arg Ala Arg Leu Met Gln Ala Leu Pro Pro Gly Gly Ala Met Leu243524402445Ala Ala Ala Ala Gly Glu Lys Glu Leu Arg Pro Leu Leu Ala Asp245024552460Arg Ala Asp Arg Val Gly Ile Ala Ala Val Asn Ala Pro Glu Ser246524702475Val Val Leu Ser Gly Asp Arg Asp Ala Leu Asp Asp Ile Ala Gly248024852490Arg Leu Asp Gly Gln Gly Val Arg Ser Arg Trp Leu Arg Val Ser249525002505
His Ala Phe His Ser His Arg Met Asp Pro Met Leu Glu Glu Phe251025152520Ala Glu Ile Ala Arg Ser Val Asp Tyr Arg Ser Pro Gly Leu Pro252525302535Ala Val Ser Thr Leu Thr Gly Glu Leu Asp Glu Val Gly Met Met254025452550Ala Thr Pro Glu Tyr Trp Val Arg Gln Val Arg Glu Pro Val Arg255525602565Phe Ala Asp Gly Val Ala Ala Leu Ala Ala His Gly Val Ser Ser257025752580Ile Val Glu Val Gly Pro Asp Gly Val Leu Ser Ala Leu Val Gln258525902595Glu Cys Ala Ala Gly Ser Asp Gln Gly Gly Arg Val Ala Ala Val260026052610Pro Leu Met Arg Ser Asn Cys Asp Glu Ala Gln Lys Val Ile Thr261526202625Ala Leu Ala Gln Val His Ala Arg Gly Ala Glu Val Asp Trp Arg263026352640Ser Phe Phe Ala Gly Thr Gly Ala Lys Gln Val Glu Leu Pro Thr264526502655Tyr Ala Phe Gln Arg Gln Arg Tyr Trp Leu Asp Ser Pro Ser Glu266026652670Pro Val Gly Gln Ser Ala Asp Leu Ala Pro Gln Ser Gly Phe Trp267526802685Glu Leu Val Glu Gln Glu Asp Val Ser Ala Leu Ser Ala Ala Leu269026952700Asn Ile Thr Gly Asp Pro Asp Val Gln Ala Ser Leu Glu Ser Val270527102715Val Pro Val Leu Ser Ser Trp His Arg Arg Ile Arg Asn Glu Ser272027252730Leu Val His Gln Trp Arg Tyr Arg Ile Ser Trp His Glu Arg Ala273527402745Asp Leu Pro Asp Arg Ser Leu Ser Gly Thr Trp Leu Val Val Val275027552760Pro Glu Gly Trp Ser Thr Ser Gln Gln Val Leu Arg Phe Arg Glu276527702775Met Phe Glu Glu Arg Gly Cys Ala Ala Val Leu Phe Glu Leu Ala278027852790Gly His Asp Glu Glu Ala Leu Val Gln Arg Phe Arg Ser Leu Pro279528002805
Val Ala Ser Gly Gly Ile Ser Gly Val Leu Ser Leu Leu Ala Leu281028152820Asp Glu Ser Pro Ser Ser Ser Asn Ala Ala Leu Pro Asn Gly Ala282528302835Leu Asn Ser Leu Val Leu Leu Arg Ala Leu Arg Thr Ala Asp Val284028452850Pro Ala Pro Leu Trp Leu Ala Thr Cys Gly Gly Val Ala Val Gly285528602865Asp Val Pro Val Asn Pro Gly Gln Ala Leu Met Trp Gly Leu Gly287028752880Arg Val Val Gly Leu Glu Asn Pro Asp Trp Trp Gly Gly Leu Val288528902895Asp Val Pro Asp Leu Leu Asp Lys Asp Ala Gln Glu Arg Leu Ser290029052910Val Val Leu Ala Gly Leu Gly Glu Asp Glu Ile Ala Val Arg Pro291529202925Asp Gly Val Phe Val Arg Arg Leu Glu Arg Ala Asp Leu Pro Asp293029352940Met Gly Ser Ala Trp Arg Pro Arg Gly Thr Val Leu Val Thr Gly294529502955Gly Thr Gly Gly Leu Gly Ala His Val Ala Arg Trp Leu Ala Gly296029652970Ala Gly Ala Glu His Val Val Leu Thr Ser Arg Arg Gly Ala Glu297529802985Ala Pro Gly Ala Gly Asp Leu Arg Ala Glu Leu Glu Ala Leu Gly299029953000Ala Arg Val Ser Ile Arg Ser Cys Asp Val Ala Asp Arg Asp Ala300530103015Leu Ala Glu Val Leu Ala Thr Ile Pro Asp Asp Cys Pro Leu Thr302030253030Ala Val Met His Ala Ala Gly Val Val Glu Val Gly Asp Val Ala303530403045Ser Met Cys Leu Thr Asp Phe Ile Gly Val Leu Ser Ala Lys Val305030553060Gly Gly Ala Ala Asn Leu Asp Glu Leu Leu Ala Asp Val Glu Leu306530703075Asp Ala Phe Val Leu Phe Ser Ser Val Ser Gly Val Trp Gly Ala308030853090Gly Gly Gln Gly Ala Tyr Ala Ala Ala Asn Ala Tyr Leu Asp Ala309531003105
Leu Ala Gln Gln Arg Arg Ala Arg Gly Leu Ala Gly Thr Ala Val311031153120Ala Trp Gly Pro Trp Ala Gly Asp Gly Met Ala Ala Gly Glu Gly312531303135Gly Ala Gln Leu Arg Arg Thr Gly Leu Val Pro Met Ala Ala Asp314031453150Arg Ala Leu Leu Ala Leu Gln Gly Ala Leu Asp Arg Asp Glu Thr315531603165Ser Leu Val Val Ala Asp Met Ala Trp Glu Arg Phe Ala Pro Val317031753180Phe Ala Met Ser Arg Arg Arg Pro Leu Leu Asp Glu Leu Pro Glu318531903195Ala Gln Gln Ala Leu Ala Asp Ala Glu Asn Thr Thr Gly Ala Ala320032053210Asp Ser Ala Gly Pro Leu Gln Arg Ile Val Gly Met Ala Ala Ala321532203225Glu Arg Arg Arg Ala Met Met Glu Leu Val Leu Ala Glu Thr Ser323032353240Ile Val Leu Gly His Asn Gly Ser Asp Ala Val Ser Pro Asp Arg324532503255Ala Phe Gln Glu Leu Gly Phe Asp Ser Leu Met Ala Val Glu Leu326032653270Arg Asn Arg Leu Gly Glu Ala Thr Gly Leu Ser Leu Pro Thr Thr327532803285Leu Ile Phe Asp Tyr Pro Ser Pro Ser Ala Leu Ala Glu Gln Leu329032953300Val Gly Glu Leu Val Gly Ala Gln Pro Ala Thr Thr Val Val Ala330533103315Gly Ala Asp Pro Val Asp Asp Pro Val Val Val Val Ala Met Gly332033253330Cys Arg Tyr Pro Gly Asp Val Cys Ser Pro Glu Glu Leu Trp Gln333533403345Leu Val Ser Ala Gly Arg Asp Ala Val Ser Thr Phe Pro Thr Asp335033553360Arg Gly Trp Asp Cys Asp Ala Leu Phe Asp Pro Asp Pro Asp Arg336533703375Ala Gly Arg Thr Tyr Val Arg Glu Gly Ala Phe Leu Thr Gly Ala338033853390Asp Arg Phe Asp Ala Gly Phe Phe Gly Ile Ser Pro Arg Glu Ala339534003405
Arg Ala Met Asp Pro Gln Gln Arg Leu Leu Leu Glu Val Ala Trp341034153420Glu Val Phe Glu Arg Ala Gly Ile Ala Pro Leu Ser Leu Arg Gly342534303435Ser Arg Thr Gly Val Phe Ala Gly Thr Asn Gly Gln Asp His Gly344034453450Ala Lys Val Ala Ala Ala Pro Glu Ala Ala Gly His Leu Leu Thr345534603465Gly Asn Ala Ala Ser Val Met Ala Gly Arg Ile Ser Tyr Thr Phe347034753480Gly Leu Glu Gly Pro Ala Val Ala Val Asp Thr Ala Cys Ser Ser348534903495Ser Leu Val Ala Leu His Leu Ala Cys Gln Ser Leu Arg Ser Gly350035053510Glu Cys Asp Met Ala Leu Ala Gly Gly Val Thr Val Met Ser Thr351535203525Pro Leu Ala Phe Leu Glu Phe Ser Arg Gln Arg Gly Leu Ala Pro353035353540Asp Gly Arg Cys Lys Ser Phe Ala Ala Ala Ala Asp Gly Thr Gly354535503555Trp Gly Glu Gly Ala Gly Leu Val Leu Leu Glu Arg Leu Ser Asp356035653570Ala Arg Arg Asn Gly His Arg Val Leu Ala Val Val Arg Gly Ser357535803585Ala Val Asn Gln Asp Gly Ala Ser Asn Gly Leu Thr Ala Pro Asn359035953600Gly Pro Ser Gln Gln Arg Val Ile Arg Gln Ala Leu Ala Asn Ala360536103615Gly Leu Ser Ala Ser Asp Val Asp Val Val Glu Ala His Gly Thr362036253630Gly Thr Gly Leu Gly Asp Pro Ile Glu Ala Gln Ala Leu Ile Ala363536403645Ala Tyr Gly Gln Gly Arg Asp Pro Glu Arg Ala Leu Trp Leu Gly365036553660Ser Ile Lys Ser Asn Ile Gly His Thr Gln Ala Ala Ala Gly Val366536703675Ala Gly Val Ile Lys Met Val Gln Ala Met Arg His Gly Glu Leu368036853690Pro Ala Thr Leu His Val Asp Lys Pro Thr Pro Gln Val Asp Trp369537003705
Ser Ala Gly Ala Val Arg Leu Leu Thr Gly Asn Thr Pro Trp Pro371037153720Glu Ser Gly Arg Pro Arg Arg Ala Gly Val Ser Ser Phe Gly Ile372537303735Ser Gly Thr Asn Ala His Leu Ile Leu Glu Gln Pro Pro Ser Glu374037453750Pro Ala Glu Ile Asp Arg Ser Asn Arg Arg Val Thr Ala His Pro375537603765Ala Val Ile Pro Trp Met Leu Ser Ala Arg Ser Leu Thr Ala Leu377037753780Gln Ala Gln Ala Ala Ala Leu Gln Gly Arg Leu Asp Arg Val Pro378537903795Gly Ala Ser Pro Leu Asp Leu Gly Tyr Ser Leu Ala Thr Thr Arg380038053810Ser Val Leu Asp Glu Arg Ala Val Val Trp Gly Ala Asp Arg Glu381538203825Thr Leu Leu Ser Arg Leu Ala Ala Leu Ala Asp Gly Arg Thr Ala383038353840Pro Gly Val Val Thr Gly Ala Ala Asn Ser Gly Gly Arg Ile Gly384538503855Phe Val Phe Ser Gly Gln Gly Ser Gln Trp Leu Gly Met Gly Lys386038653870Ala Leu Cys Ala Ala Phe Pro Ala Phe Ala Asp Ala Phe Glu Glu387538803885Ala Cys Asp Ala Leu Gly Ala His Leu Gly Ala His Leu Gly Ala389038953900Asp Leu Gly Val Asp Val Arg Gly Val Leu Phe Gly Ala Asp Glu390539103915Gln Val Leu Asp Arg Thr Leu Trp Ala Gln Pro Gly Ile Phe Ala392039253930Val Gln Val Gly Leu Leu Gly Leu Leu Arg Ser Trp Gly Val Arg393539403945Pro Asp Ala Val Leu Gly His Ser Val Gly Glu Leu Ala Ala Ala395039553960His Ala Ala Gly Val Leu Ser Leu Pro Asp Ala Ala Arg Leu Val396539703975Ala Ala Arg Ala Ser Leu Met Gln Ala Leu Pro Thr Gly Gly Ala398039853990Met Leu Ala Val Ala Thr Ser Glu Ala Ala Val Glu Pro Leu Leu399540004005
Ala Gly Met Cys Asp Arg Val Ser Ile Ala Ala Ile Asn Gly Pro401040154020Glu Ser Val Val Leu Ser Gly Asp Arg Asp Val Leu Ala Glu Val402540304035Ala Gly Glu Leu Asp Ala Arg Gly Leu Arg Thr Lys Trp Leu Arg404040454050Val Ser His Ala Phe His Ser His Arg Met Gln Pro Ile Leu Asp405540604065Glu Tyr Ala Glu Thr Ala Gly Cys Val Glu Phe Gly Glu Pro Val407040754080Val Pro Ile Val Ser Ala Ala Thr Gly Ala Leu Asp Thr Ala Gly408540904095Leu Met Cys Ala Ala Gly Tyr Trp Val Arg Gln Val Arg Asp Pro410041054110Val Arg Phe Gly Asp Gly Val Gln Ala Leu Val Asp Gln Gly Val411541204125Asp Thr Ile Val Glu Phe Gly Pro Asp Gly Ala Leu Ser Ala Leu413041354140Val Gln Gln Cys Leu Ala Gly Ser Asp Gln Ala Gly Arg Val Ala414541504155Ala Ile Pro Leu Met Arg Arg Asp Arg Asp Glu Val Glu Thr Ala416041654170Val Ala Ala Leu Ala His Val His Val Arg Gly Gly Ala Val Asp417541804185Trp Ser Ala Cys Phe Ala Gly Thr Gly Ala Arg Thr Val Glu Leu4l904l954200Pro Thr Tyr Ala Phe Gln Arg Gln Arg Tyr Trp Leu Ala Gly Gln420542104215Ala Asp Gly Arg Gly Gly Asp Val Val Ala Asp Pro Val Asn Ala422042254230Arg Phe Trp Glu Leu Val Glu Arg Ala Asp Pro Glu Pro Leu Val423542404245Asp Glu Leu Cys Ile Asp Arg Asp Gln Pro Phe Arg Glu Val Leu425042554260Pro Val Leu Ala Ser Trp Arg Glu Lys Gln Arg Gln Lys Ala Val426542704275Thr Asp Ser Trp Arg Tyr Gln Val Arg Trp Arg Ser Val Glu Val428042854290Gln Ser Ala Ala Ser Leu Arg Gly Val Trp Leu Val Val Leu Pro429543004305
Ala Asp Gly Leu Arg Asp Gln Pro Ala Ala Val Ile Asp Ala Leu431043154320Ile Ala Arg Gly Ala Glu Val Ala Val Leu Glu Leu Thr Glu Gln432543304335Asp Phe Gln Arg Gly Ala Leu Val Asp Lys Val Arg Ala Val Ile434043454350Ala Asp Arg Thr Glu Val Thr Gly Val Leu Ser Leu Leu Ala Met435543604365Asp Gly Met Pro Cys Ala Glu His Pro His Leu Ser Arg Gly Val437043754380Ala Ala Thr Val Ile Leu Thr Gln Val Leu Gly Asp Ala Gly Val438543904395Ser Ala Pro Leu Trp Leu Ala Thr Thr Gly Gly Val Glu Val Gly440044054410Thr Glu Asp Gly Pro Ala Asp Pro Asp His Gly Leu Ile Trp Gly441544204425Leu Gly Arg Val Val Gly Leu Glu His Pro Gln Arg Trp Gly Gly443044354440Leu Ile Asp Leu Pro Ala Thr Leu Asp Glu Thr Ser Arg Asn Gly444544504455Leu Val Ala Ala Leu Ala Gly Thr Ala Ala Glu Asp Gln Leu Ala446044654470Val Arg Ser Ser Gly Leu Phe Val Arg Arg Val Val Arg Ala Ala447544804485Gln Asn Ser Arg Ser Gly Thr Trp Arg Ser Arg Gly Thr Val Leu449044954500Ile Thr Gly Gly Thr Gly Ala Leu Gly Ala Glu Val Ala Arg Trp450545104515Leu Ala Arg Arg Gly Ala Glu His Leu Val Leu Ile Ser Arg Arg452045254530Gly Pro Glu Ala Pro Gly Ala Ala Asp Leu Gln Ala Glu Leu Thr453545404545Glu Leu Gly Val Lys Val Thr Val Val Ala Cys Asp Val Thr Asp455045554560Gly Asp Glu Leu Arg Ala Val Leu Ala Ala Val Pro Thr Glu His456545704575Pro Leu Ser Ala Val Val His Thr Ala Gly Val Gly Thr Pro Ala458045854590Asn Leu Ala Glu Thr Thr Leu Ala Gln Phe Ala Asp Val Leu Ser459546004605
Ala Lys Val Val Gly Ala Ala Asn Leu Asp Arg Leu Leu Gly Gly461046154620Gln Pro Leu Asp Ala Phe Val Leu Phe Ser Ser Ile Ser Gly Val462546304635Trp Gly Ala Gly Gly Gln Gly Ala Tyr Ser Ala Ala Asn Ala Tyr464046454650Leu Asp Ala Leu Ala Glu Arg Arg Arg Ala Cys Gly Arg Pro Ala465546604665Thr Cys Val Ala Trp Gly Pro Trp Ala Gly Ala Gly Met Ala Val467046754680Gln Glu Gly Asn Glu Ala His Leu Arg Arg Arg Gly Leu Val Pro468546904695Met Glu Pro Gln Ser Ala Leu Ser Ala Leu Gln Gln Ala Leu Ser470047054710Arg Arg Glu Thr Ala Ile Thr Val Ala Asp Val Asp Trp Glu Arg471547204725Phe Ala Ala Thr Phe Thr Ala Ala Arg Pro Arg Pro Leu Leu Asp473047354740Glu Ile Val Asp Leu Arg Pro Asn Thr Glu Thr Ala Glu Lys His474547504755Gly Ala Gly Glu Leu Gly Gln Gln Leu Ala Ala Leu Pro Ala Ala476047654770Glu Arg Gly His Leu Leu Leu Glu Val Val Leu Ala Glu Thr Ala477547804785Asn Thr Leu Gly His Asp Ser Ala Glu Ala Val Gln Pro Asp Arg479047954800Thr Phe Ala Glu Leu Gly Phe Asp Ser Leu Thr Ala Val Glu Leu480548104815Arg Asn Arg Lau Asn Ala Val Thr Gly Leu Arg Leu Pro Pro Thr482048254830Leu Val Phe Asp His Pro Thr Pro Leu Ala Val Ser Glu Gln Leu483 548404845Val Pro Ala Leu Val Ala Glu Pro Gly Asp Gly Ile Glu Ser Leu485048554860Leu Ala Glu Leu Asp Arg Leu Asp Thr Thr Leu Ala Gln Arg Pro486548704875Ser Ile Pro Pro Glu Asp Gln Ala Lys Val Ala Glu Arg Leu Gln488048854890Ala Leu Ile Ala Lys Trp Asp Gly Ala Arg Asp Gly Thr Ala Lys489549004905
Val Thr Ser Pro Gln Ser Leu Thr Ala Ala Thr Asp Asp Glu Ile491049154920Phe Asp Leu Ile Asp Arg Lys Phe Arg Arg49254930<210>7<211>5564<212>PRT<213>刺糖多胞菌NRRL30141<400>7Met Ala Asr Glu Glu Lys Leu Arg Glu Tyr Leu Lys Arg Val Val Val1 5 10 15Glu Leu Glu Glu Ala His Glu Arg Leu His Glu Leu Glu Arg Gln Glu20 25 30His Asp Pro Ile Ala Ile Val Ser Met Gly Cys Arg Tyr Pro Gly Gly35 40 45Val Ser Thr Pro Glu Glu Leu Trp Arg Leu Val Val Asp Gly Gly Asp50 55 60Ala Ile Ala Asn Phe Pro Glu Asp Arg Gly Trp Asn Leu Gly Glu Leu65 70 75 80Phe Asp Pro Asp Pro Gly Arg Ala Gly Thr Ser Tyr Val Arg Glu Gly85 90 95Gly Phe Leu Arg Gly Val Ala Asp Phe Asp Ala Gly Leu Phe Gly Ile100 105 110Ser Pro Arg Glu Ala Gln Ala Met Asp Pro Gln Gln Arg Leu Leu Leu115 120 125Glu Ile Ser Trp Glu Val Leu Glu Arg Ala Gly Ile Asp Pro Phe Ser130 135 140Leu Arg Gly Thr Lys Thr Ser Val Phe Ala Gly Leu Ile Tyr His Asp145 150 155 160Tyr Ala Ser Arg Phe Ser Lys Thr Pro Ala Glu Phe Glu Gly Tyr Phe165 170 175Ala Thr Gly Asn Ala Gly Ser Val Ala Ser Gly Arg Val Ala Tyr Thr180 185 190Phe Gly Leu Glu Gly Pro Ala Val Thr Val Asp Thr Ala Cys Ser Ser195 200 205Ser Leu Val Ala Leu His Leu Ala Cys Gln Ser Leu Arg Leu Gly Glu210 215 220Cys Asp Leu Ala Leu Ala Gly Gly Ile Ser Val Met Ala Thr Pro Gly225 230235 240Ala Phe Val Glu Phe Ser Arg Gln Arg Ala Leu Ala Ser Asp Gly Arg
245 250 255Cys Lys Pro Phe Ala Asp Ala Ala Asp Gly Thr Gly Trp Gly Glu Gly260 265 270Ala Gly Met Leu Leu Leu Glu Arg Leu Ser Asp Ala Arg Arg Asr Gly275 280 285His Pro Val Leu Ala Ala Val Val Gly Ser Ala Ile Asn Gln Asp Gly290 295 300Met Ser Asn Gly Leu Thr Ala Pro Ser Gly Pro Ala Gln Gln Arg Val305 310 315 320Ile Arg Gln Ala Leu Thr Asn Ala Gly Leu Ser Pro Ala Glu Val Asp325 330 335Val Val Glu Ala His Gly Thr Gly Thr Ala Leu Gly Asp Pro Ile Glu340 345 350Ala Arg Ala Leu Ile Ala Thr Tyr Gly Ala Asn Arg Ser Ala Asp His355 360 365Pro Leu Leu Leu Gly Ser Leu Lys Ser Asn Ile Gly His Thr Gln Ala370 375 380Ala Ala Gly Val Ala Gly Val Ile Lys Ser Val Met Ala Ile Arg His385 390 395 400Arg Glu Met Pro Arg Ser Leu His Ile Asp Gln Pro Ser Arg His Val405 410 415Asp Trp Ser Ala Gly Ala Val Arg Leu Leu Thr Asp Ser Val Asp Trp420 425 430Ala Asp Pro Gly Arg Pro Arg Arg Ala Gly Val Ser Ser Phe Gly Met435 440 445Ser Gly Thr Asn Ala His Leu Ile Val Glu Glu Val Ser Asp Glu Pro450 455 460Val Ser Gly Ser Thr Glu Pro Thr Gly Ala Leu Pro Trp Pro Leu Ser465 470 475 480Gly Lys Thr Glu Thr Ala Leu Arg Glu Gln Ala Ala Glu Leu Leu Ser485 490 495Ala Val Thr Ala His Pro Glu Pro Gly Leu Gly Asn Val Gly Tyr Ser500 505 510Leu Ala Thr Gly Arg Ala Ala Met Glu His Arg Ala Val Val Val Ala515 520 525Glu Asp Arg Asp Ser Phe Val Ala Gly Leu Thr Ala Leu Ala Ala Gly530 535 540Val Pro Ala Ala Asn Val Val Gln Gly Ala Ala Asp Cys Lys Gly Lys545 550 555 560Val Ala Phe Val Phe Pro Gly Gln Gly Ser His Trp Gln Gly Met Ala
565 570 575Arg Glu Leu Phe Glu Ser Ser Pro Val Phe Arg Arg Lys Leu Glu GIu580 585 590Cys Ala Ala Ala Thr Ala Pro Tyr Val Asp Trp Ser Leu Leu Gly Val595 600 605Leu Arg Gly Asp Pro Asp Ala Pro Ala Leu Asp Arg Asp Asp Val Ile610 615 620Gln Phe Ala Leu Phe Ala Met Met Val Ser Leu Ala Glu Leu Trp Arg625 630 635 640Ser Cys Gly Val Glu Pro Ala Ala Val Val Gly His Ser Gln Gly Glu645 650 655Ile Ala Ala Ala His Val Ala Gly Ala Leu Ser Leu Thr Asp Ala Val660 665 670Arg Ile Val Ala Ala Arg Cys Asn Ala Val ser Val Leu Ala Gly Lys675 680 685Gly Gly Met Leu Ala Ile Ala Leu Pro Glu Ser Ala Val Val Lys Arg690 695 700Ile Ala Gly Leu Pro Glu Leu Thr Val Ala Ala Val Asn Gly Pro Gly705 710 715 720Ser Thr Val Val Ser Gly Glu Pro Ser Ala Leu Glu Arg Leu Gln Thr725 730 735Glu Leu Ser Ala Glu Asn Val Gln Ala Arg Arg Val Arg Ile Asp Tyr740 745 750Ala Ser His Ser Ala Gln Ile Ala Gln Val Gln Gly Arg Leu Leu Asp755 760 765Arg Leu Gly Glu Val Gly Ser Glu Pro Ala Glu Ile Ala Phe Tyr Ser770 775 780Thr Val Thr Gly Glu Arg Thr Asp Thr Gly Arg Leu Asp Ala Asp Tyr785 790 795 800Trp Tyr Gln Asn Leu Arg Gln Pro Val Arg Phe Gln Gln Thr Val Ala805 810 815Arg Met Ala Asp Gln Gly Tyr Arg Phe Phe Val Glu Val Ser Pro His820 825 830Pro Leu Leu Thr Ala Gly Ile Gln Glu Thr Leu Glu Ala Ala Asp Ala835 840 845Asp Ala Gly Gly Val Val Val Gly Ser Leu Arg Gly Gly Glu Gly Gly850 855 860Ser Arg Arg Trp Leu Thr Ser Leu Ala Glu Cys Gln Val Arg Gly Leu865 870 875 880Pro Val Asn Trp Glu Gln Val Phe Leu Asp Thr Gly Ala Arg Arg Val
885 890 895Pro Leu Pro Thr Tyr Pro Phe Gln Arg Gln Arg Tyr Trp Leu Glu Ser900905 910Ala Glu Tyr Asp Ala Gly Asp Leu Gly Ser Val Gly Leu Arg Ser Ala915 920 925Glu His Pro Leu Leu Gly Ala Ala Val Thr Leu Ala Asp Ala Gly Gly930 935 940Phe Leu Leu Thr Gly Lys Leu Ser Val Lys Thr Gln Pro Trp Leu Ala945 950 955 960Asp His Ala Val Arg Gly Ala Ile Leu Leu Pro Gly Thr Ala Phe Val965 970 975Glu Met Leu Ile Arg Ala Ala Asp Gln Val Gly Cys Asp Leu Ile Glu980 985 990Glu Leu Ser Leu Thr Thr Pro Leu Val Leu Pro Ala Thr Gly Ala Val995 10001005Gln Val Gln Ile Ala Val Gly Gly Pro Asp Glu Ala Gly Arg Arg101010151020Ser Val Arg Val His Ser Cys Arg Asp Asp Ser Val Pro Gln Asp102510301035Ser Trp Thr Cys His Ala Thr Gly Thr Leu Thr Thr Ser Glu His104010451050Arg Asp Ala Gly Gln Ala Arg Asp Gly Ile Trp Pro Pro Asn Asp105510601065Ala Val Ala Val Pro Leu Asp Ser Phe Tyr Ala Arg Ala Ala Glu107010751080Arg Gly Phe Asp Phe Gly Pro Ala Phe Gln Gly Leu Gln Ala Val108510901095Trp Lys Arg Gly Asp Glu Ile Phe Ala Glu Val Gly Leu Pro Ala110011051110Ala Gln Arg Glu Asp Ala Gly Arg Phe Gly Val His Pro Ala Leu111511201125Leu Asp Ala Ala Leu Gln Ala Leu Gly Ala Ala Glu Glu Asp Pro113011351140Asp Glu Gly Trp Leu Pro Phe Ala Trp Gln Gly Val Ser Leu Lys114511501155Ala Thr Gly Ala Leu Ser Leu Arg Val His Ile Val Pro Ala Gly116011651170Ala Asn Ala Val Ser Val Phe Thr Thr Asp Ala Thr Gly Gln Ala117511801185Val Leu Ser Ile Asp Ssr Leu Val Leu Arg Lys Ile Ser Asp Glu
119011951200Gln Leu Ala Ala Val Arg Ala Met Asp His Glu Ser Leu Phe Arg120512101215Val Asp Trp Arg Arg Ile Ser Pro Gly Ala Ala Lys Pro Val Ser122012251230Trp Ala Val Ile Gly Asn Asp Glu Leu Ala Arg Ala Cys Gly Ser123512401245Ala Leu Gly Thr Glu Leu His Pro Asp Leu Thr Gly Leu Ala Asp125012551260Pro Pro Pro Asp Val Val Val Val Pro Cys Gly Ala Phe His Gln126512701275Asp Leu Glu Val Ala Ser Glu Ala Arg Ala Ala Thr Gln Arg Val128012851290Leu Asp Leu Ile Gln Gly Trp Leu Ala Ala Glu Arg Phe Ala Gly129513001305Ser Arg Leu Val Val Val Thr Cys Gly Ala Val Ser Thr Gly Pro131013151320Ala Glu Gly Val Ser Asp Leu Val His Ala Ala Ser Trp Gly Leu132513301335Leu Arg Ser Ala Gln Ser Glu Asn Pro Asn Arg Phe Val Leu Val134013451350Asp Val Asp Ala Thr Ala Glu Ser Trp Arg Ala Leu Ala Ala Ala135513601365Val Arg Ser Gly Glu Pro Gln Leu Ala Leu Arg Ala Gly Glu Val137013751380Arg Val Pro Arg Leu Thr Arg Cys Val Ala Ala Glu Asp Ser Arg138513901395Ile Pro Val Pro Gly Ala Asp Gly Thr Val Leu Ile Ser Gly Gly140014051410Thr Gly Leu Leu Gly Gly Leu Val Ala Arg His Leu Val Ala Glu141514201425Arg Gly Val Arg Arg Leu Val Leu Ala Gly Arg Arg Gly Trp Ser143014351440Ala Pro Gly Val Thr Glu Leu Val Asp Glu Leu Val Gly Leu Gly144514501455Ala Val Val Glu Val Ala Ser Cys Asp Val Gly Asp Arg Ala Gln146014651470Leu Asp Arg Leu Leu Thr Thr Ile Ser Ala Glu Phe Pro Leu Arg147514801485Gly Val Val His Ala Ala Gly Ala Leu Ala Asp Gly Val Val Glu
149014951500Ser Leu Thr Pro Glu His Val Ala Lys Val Phe Gly Pro Lys Val150515101515Ala Gly Ala Trp His Leu His Glu Leu Thr Arg Glu Leu Asp Leu152015251530Ser Phe Phe Val Leu Phe Ser Ser Phe Ser Gly Val Val Gly Ala153515401545Ala Gly Gln Gly Asn Tyr Ala Ala Ala Asn Ala Phe Leu Asp Gly155015551560Leu Ala Gln His Arg Arg Thr Ala Gly Leu Pro Ala Val Ser Leu156515701575Ala Trp Gly Leu Trp Glu Pro Thr Ser Gly Met Thr Gly Ala Leu158015851590Asp Ala Ala Asp Arg Ser Arg Ile Ser Arg Thr Asn Pro Pro Met159516001605Ser Ala Glu Asp Gly Leu Arg Leu Phe Glu Met Ala Phe His Val161016151620Pro Gly Glu Ser Leu Leu Val Pro Val His Ile Asp Leu Asn Ala162516301635Leu Arg Ala Asp Ala Ala Asp Gly Gly Val Pro Ala Leu Leu His164016451650Asp Leu Val Pro Ala Pro Val Arg Arg Ser Ala Val Asn Glu Ser165516601665Glu Asp Val Thr Gly Leu Val Gly Arg Leu Arg Arg Leu Pro Asp167016751680Leu Asp Gln Glu Thr Leu Leu Leu Gly Leu Val Arg Glu His Val168516901695Ser Ala Val Leu Gly Tyr Ser Gly Ala Val Glu Val Gly Val Glu170017051710Arg Ala Phe Arg Asp Leu Gly Phe Asp Ser Leu Ser Gly Val Glu171517201725Leu Arg Asn Arg Leu Gly Gly Val Leu Gly Val Arg Leu Pro Ala173017351740Thr Ala Val Phe Asp Tyr Pro Thr Pro Arg Ala Leu Val Arg Phe174517501755Leu Arg Asp Lys Leu Ile Gly Gly Val Glu Ala Arg Asn Ser Ala176017651770Pro Ala Val Val Glu Ala Ala Ser Gly Asp Asp Pro Val Val Ile177517801785Val Gly Met Gly Cys Arg Phe Pro Gly Gly Val Ser Ser Pro Glu
179017951800Glu Leu Trp Arg Leu Val Ala Gly Gly Leu Asp Ala Val Ala Glu180518101815Phe Pro Asp Asp Arg Gly Trp Asp Gln Ala Gly Leu Phe Asp Pro18201825183 0Asp Pro Asp Arg Leu Gly Thr Ser Tyr Val Cys Glu Gly Gly Phe183518401845Leu Arg Asp Ala Ala Glu Phe Asp Ala Gly Phe Phe Gly Ile Ser185018551860Pro Arg Glu Ala Leu Ala Met Asp Pro Gln Gln Arg Leu Leu Leu186518701875Glu Ile Ala Trp Glu Thr Leu Glu Arg Ala Gly Ile Asp Pro Leu188018851890Ser Leu Arg Gly Ser Arg Thr Gly Val Phe Ala Gly Leu Met His189519001905His Asp Tyr Gly Ala Arg Phe Val Thr Arg Ala Pro Glu Gly Phe191019151920Glu Gly Tyr Leu Gly Asn Gly Ser Ala Gly Gly Val Phe Ser Gly192519301935Arg Val Ala Tyr Ser Phe Gly Phe Glu Gly Pro Ala Val Thr Val194019451950Asp Thr Ala Cys Ser Ser Ser Leu Val Ser Met His Leu Ala Gly195519601965Gln Ala Leu Arg Ser Gly Glu Cys Asp Leu Ala Leu Ala Gly Gly197019751980Val Thr Val Met Ala Thr Pro Gly Met Phe Val Glu Phe Ser Arg198519901995Gln Arg Gly Leu Ala Ala Asp Gly Arg Cys Lys Ser Phe Ala Ala200020052010Ala Ala Asp Gly Thr Gly Trp Gly Glu Gly Ala Gly Leu Val Leu201520202025Leu Glu Arg Leu Ser Asp Ala Arg Arg Asn Gly His Ala Val Leu203020352040Ala Val Val Arg Gly Ser Ala Val Asn Gln Asp Gly Ala Ser Asn204520502055Gly Leu Thr Ala Pro Asn Gly Pro Ser Gln Gln Arg Val Ile Thr206020652070Gln Ala Leu Ala Ser Ala Gly Leu Ser Val Ser Asp Val Asp Ala207520802085Val Glu Ala His Gly Thr Gly Thr Arg Leu Gly Asp Pro Ile Glu
209020952100Ala Gln Ala Leu Ile Ala Thr Tyr Gly Gln Glu Arg Asp Arg Asp210521102115Arg Pro Leu Trp Leu Gly Ser Val Lys Ser Asn Ile Gly His Thr212021252130Gln Ala Ala Ala Gly Val Ala Gly Val Ile Lys Met Val Met Ala213521402145Met Arg His Glu Gln Leu Pro Ala Thr Leu His Val Asp Glu Pro215021552160Thr Pro Glu Val Asp Trp Ser Ala Gly Glu Val Gln Leu Leu Thr216521702175Glu Asn Thr Pro Trp Pro Asp Ser Gly His Pro Arg Arg Ala Gly218021852190Val Ser Ser Phe Gly Ile Ser Gly Thr Asn Ala His Val Ile Leu219522002205Glu Gln Ala Ser Asn Thr Pro Asp Glu Ile Ala Gln Ser Asn Gly221022152220Pro Glu Ser Glu Ser Thr Val Asp Ile Pro Ala Val Pro LeuIle222522302235Val Ser Gly Arg Thr Pro Glu Ala Leu Ser Ala Gln Ala Ser Ala224022452250Leu Met Ser Tyr Leu Asp Asn Arg Pro Asp Ile Ser Ser Leu Asp225522602265Ala Ala Phe Ser Leu Ala Ser Ser Arg Ala Ala Leu Glu Glu Arg227022752280Ala Val Val Leu Gly Ala Asp Arg Glu Ala Leu Leu Ser Gly Leu228522902295Glu Ala Leu Ala Ala Gly Arg Asp Ala Ser Gly Val Val Ser Gly230023052310Ser Leu Ile Ser Gly Gly Val Gly Phe Val Phe Ser Gly Gln Gly231523202325Gly Gln Trp Leu Gly Met Gly Arg Gly Leu Tyr Ser Ala Phe Pro233023352340Val Phe Ala Asp Ala Phe Asp Glu Ala Cys Ala Gly Leu Asp Ala234523502355His Leu Gly Gln Gln Val Gly Val Arg Asp Val Val Phe Gly Ser236023652370Asp Gly Ser Leu Leu Asp Arg Thr Leu Trp Ala Gln Ser Gly Leu237523802385Phe Ala Leu Gln Val Gly Leu Leu Arg Leu Leu Gly Ser Trp Gly
239023952400Val Arg Pro Gly Val Val Met Gly His Ser Val Gly Glu Phe Ala240524102415Ala Ala Phe Ala Ala Gly Val Leu Ser Leu Pro Asp Ala Ala Arg242024252430Leu Val Ala Gly Arg Ala Arg Leu Met Gln Ala Leu Pro Asp Gly243524402445Gly Ala Met Leu Ala Val Ala Ala Gly Glu Glu Gln Leu Arg Pro245024552460Leu Leu Ala Ala Arg Gly Glu Gly Val Gly Ile Ala Ala Val Asn246524702475Ala Ser Glu Ser Val Val Leu Ser Gly Asp Arg Glu Val Leu Glu248024852490Asp Ile Ala Gly Gly Leu Asp Gly Gln Gly Val Arg Trp Arg Trp249525002505Leu Arg Val Ser His Ala Phe His Ser Tyr Arg Met Asp Pro Met251025152520Leu Gln Glu Phe Thr Asp Ile Ala Gly Ser Val Asp Tyr Arg Arg252525302535Cys Asp Leu Pro Val Val Ser Thr Leu Thr Gly Glu Leu Asp Thr254025452550Ala Gly Met Leu Ala Thr Pro Gly Tyr Trp Val Arg Gln Val Arg255525602565Glu Pro Val Arg Phe Ala Asp Gly Val Arg Ala Leu Ala Gln Gln257025752580Gly Val Gly Thr Ile Phe Glu Leu Gly Pro Asp Ala Ile Leu Ser258525902595Ala Leu Ile Pro Asp Cys His Ser Trp Gly Asp Gln Thr Val Pro260026052610Ile Pro Leu Leu Arg Lys Asp Arg Ala Glu Pro Glu Thr Val Val261526202625Ala Ala Val Ala Arg Ala His Thr Arg Gly Val Gln Val Asp Trp263026352640Ser Ala Phe Phe Ala Gly Thr Gly Ala Gly Arg Val Glu Leu Pro264526502655Thr Tyr Ala Phe Gln Arg Gln Arg Tyr Trp Leu Glu Ser Ser Val266026652670Ser Gly Asp Val Thr Gly Ile Gly Leu Ala Gly Ala Glu His Pro267526802685Leu Lau Gly Ala Val Val Val Leu Ala Asp Gly Asp Gly Met Val
269026952700Leu Thr Gly Arg Leu Ser Val Gly Thr His Arg Trp Leu Ala Glu270527102715His Arg Val Leu Gly Glu Val Val Val Pro Gly Thr Ala Ile Leu272027252730Glu Met Val Leu His Ala Gly Ala Arg Val Gly Cys Gly Arg Val273527402745Glu Glu Leu Thr Leu Glu Ala Pro Leu Val Val Pro Glu Arg Asp275027552760Ala Ile Glu Ile Gln Leu Leu Val Asn Ala Pro Asp Asp Lys Gly276527702775Arg Arg Ser Val Ser Leu His Ser Arg Pro Ala Gly Gly Ser Gly278027852790Gly Gly Gly Trp Thr Arg His Ala Thr Gly Glu Leu Val Val Ala279528002805Gly Thr Gly Gly Gly Ala Val Thr Gly Trp Ser Thr Glu Gly Ala281028152820Glu Pro Val Ala Leu Gly Glu Phe Tyr Val Val Gln Ala Gly Asn282528302835Gly Phe Glu Tyr Gly Pro Leu Phe Gln Gly Leu Arg Ala Ala Trp284028452850Arg Arg Gly Gly Glu Val Leu Ala Glu Val Ala Leu pro Ala Ala285528602865Ala Gly Ala Met Ala Gly Phe Leu Ile Asn Pro Ala Leu Leu Asp287028752880Ala Ala Leu Gln Ala Ser Ala Leu Gly Asp Arg Pro Ala Glu Gly288528902895Gly Ala Trp Leu Pro Phe Ser Phe Thr Gly Val Glu Leu Ser Gly290029052910Gln Gly Gly Thr Ile Ser Arg Ala Arg Val Glu Ser Thr Arg Pro291529202925Asp Ala Val Ser Val Ala Val Met Asp Glu Gly Gly Arg Leu Leu293029352940Ala Ser Ile Asp Ser Leu Arg Leu Arg Pro Val Ser Ser Val Arg294529502955Leu Ala Asn Arg Asp Val Val Gly Asp Ala Leu Phe Glu Val Thr296029652970Trp Glu Pro Val Ala Thr Arg Ser Thr Val Ser Gly Arg Trp Ala297529802985Leu Leu Gly Asp Ala Val Gly Gly Met Ala Gly Leu Ile Gly Leu
299029953000Ala Pro Gly Ser Val Asp Arg Cys Ala Gly Leu Ala Glu Leu Ala300530103015Gly Asn Leu Asp Ser Gly Ala Leu Val Ala Asp Val Val Val Tyr302030253030Cys Ala Gly Glu Gln Ala Asp Pro Asp Ala Gly Val Ala Ala Leu303530403045Ala Glu Thr Arg Glu Met Leu Ala Leu Val Gln Ser Trp Leu Ala305030553060Glu Glu Arg Leu Ala Gly Ser Arg Leu Val Val Val Thr Cys Gly306530703075Ala Val Thr Thr Ala Ala Gly Asp Gly Ala Ser Lys Leu Ala His308030853090Ala Pro Leu Trp Gly Leu Leu Arg Ser Ala Gln Ser Glu Asn Pro309531003105Gly Arg Phe Val Leu Val Asp Val Asp Gly Thr Ala Glu Ser Trp311031153120Arg Ala Leu Pro Ser Ala Val Gly Ser Met Gln Pro Gln Leu Ala312531303135Val Arg Lys Gly Val Val Thr Val Pro Arg Val Ala Ser Val Pro314031453150Gly Pro Val Glu Val Pro Ala Val Val Ala Gly Pro Asp Arg Thr315531603165Val Leu Ile Ser Gly Gly Thr Gly Leu Leu Gly Gly Val Val Ala317031753180Arg His Leu Val Ala Glu Arg Gly Val Arg Arg Val Val Leu Thr318531903195Gly Arg Arg Gly Trp Asp Ala Pro Gly Ile Thr Glu Leu Val Gly320032053210Glu Leu Glu Gly Phe Gly Ala Val Val Asp Val Val Ala Cys Asp321532203225Val Ala Asp Arg Ala Gly Leu Glu Gly Leu Leu Ala Ala Val Pro323032353240Ala Glu Phe Pro Lsu Cys Gly Val Val His Ala Ala Gly Val Leu324532503255Ala Asp Gly Val Ile Glu Ser Leu Thr Pro Glu Asp Val Gly Ala326032653270Val Phe Gly Pro Lys Ala Ala Gly Ala Trp Asn Leu His Glu Leu327532803285Thr Arg Asp Met Asp Leu Ser Phe Phe Ala Leu Phe Ser Ser Leu
329032953300Ser Gly Val Thr Gly Ala Ala Gly Gln Gly Asn Tyr Ala Ala Ala330533103315Asn Thr Phe Leu Asp Ala Leu Ala His Tyr Arg Arg Ala Gln Gly332033253330Leu Pro Ala Val Ser Leu Ala Trp Gly Leu Trp Glu Gln Ser Ser333533403345Gly Met Thr Gly Arg Leu Ser Asp Val Asp Arg Ser Arg Ile Ala335033553360Arg Ser Ser Pro Pro Leu Ser Thr Lys Asp Gly Leu Arg Leu Phe336533703375Asp Ala Gly Leu Ala Leu Asp Arg Ala Ala Val Val Pro Ala Arg338033853390Leu Asp Arg Ala Phe Leu Ala Glu Gln Ala Arg Ser Gly Thr Leu339534003405Pro Ala Met Leu Thr Ala Leu Val Pro Thr Ile Thr Ser Ile Arg341034153420Arg Ser Ser Gly Thr Asp Leu Ala Asp Glu Asp Ala Leu Leu Gly342534303435Val Val Arg Glu His Ala Ala Arg Val Leu Gly Tyr Ser Gly Ala344034453450Ala Glu Val Gly Val Glu Arg Ala Phe Arg Asp Leu Gly Phe Asp345534603465Ser Leu Ser Gly Val Glu Leu Arg Asn Arg Leu Ala Gly Val Leu347034753480Gly Ala Arg Leu Pro Ala Thr Ala Val Phe Asp Tyr Pro Thr Pro348534903495Arg Ala Leu Ala Arg Phe Leu His Gln Glu Leu Ala Gly Glu Val350035053510Gly Thr Thr Pro Ala Pro Val Thr Thr Thr Thr Ala Ser Val Glu351535203525Asp Asp Leu Val Ala Ile Val Gly Met Gly Cys Arg Tyr Pro Gly353035353540Gly Val Ser Ser Pro Glu Glu Leu Trp Arg Leu Val Ala Gly Gly354535503555Val Asp Ala Val Ala Asp Phe Pro Asp Asp Arg Gly Trp Asp Leu356035653570Ala Gly Leu Phe Asp Pro Asp Pro Asp Arg Phe Gly Thr Ser Tyr357535803585Val Arg Glu Gly Gly Phe Leu Arg Asp Ala Ala Glu Phe Asp Ala
359035953600Ala Phe Phe Gly Ile Ser Pro Arg Glu Ala Leu Ala Met Asp Pro360536103615Gln Gln Arg Leu Leu Leu Glu Leu Ser Trp Glu Ala Val Glu Arg362036253630Ala Gly Ile Asp Pro Gly Ser Leu Arg Gly Ser Arg Thr Gly Val363536403645Phe Ala Gly Leu Met Tyr His Asp Tyr Ala Gly Arg Phe Ala Ala365036553660Gly Val Pro Glu Gly Phe Glu Gly Tyr Leu Gly Asn Gly Ser Ala366536703675Gly Ser Val Ala Ser Gly Arg Val Ala Tyr Ser Phe Gly Phe Glu368036853690Gly Pro Ala Val Thr Val Asp Thr Ala Cys Ser Ser Ser Leu Val369537003705Ala Leu His Leu Ala Gly Gln Ser Leu Arg Ser Gly Glu Cys Asp371037153720Leu Ala Leu Ala Gly Gly Val Thr Val Met Ala Thr Pro Ala Thr372537303735Phe Val Glu Phe Ser Arg Gln Arg Gly Leu Ala Pro Asp Gly Arg374037453750Cys Lys Ser Phe Ala Glu Ala Ala Asp Gly Thr Gly Trp Gly Glu375537603765Gly Ala Gly Leu Val Leu Leu Glu Arg Leu Ser Asp Ala Arg Arg377037753780Asn Gly His Arg Val Leu Ala Val Val Arg Gly Ser Ala Val Asn378537903795Gln Asp Gly Ala Ser Ash Gly Leu Thr Ala Pro Asn Gly Pro Ser380038053810Gln Gln Arg Val Ile Thr Gln Ala Leu Thr Ser Ala Gly Leu Ser38l538203825Val Ser Asp Val Asp Ala Val Glu Ala His Gly Thr Gly Thr Arg383038353840Leu Gly Asp Pro Ile Glu Ala Gln Ala Leu Ile Ala Thr Tyr Gly384538503855Arg Asp Arg Asp Pro Asp Arg Pro Leu Trp Leu Gly Ser Met Lys386038653870Ser Asn Ile Gly His Thr Gln Ala Ala Ala Gly Val Ala Gly Val387538803885Ile Lys Met Val Met Ala Met Arg His Gly Glu Leu Pro Arg Thr
389038953900Leu His Val Gly Glu Pro Thr Ser Glu Val Asp Trp Ser Ala Gly390539103915Ser Val Gln Leu Leu Thr Glu Asn Thr Pro Trp Pro Asp Ser Gly392039253930His Pro Arg Arg Ala Gly Val Ser Ser Phe Gly Ile Ser Gly Thr393539403945Asn Ala His Val Ile Leu Glu Gln Ser Pro Thr Ala Ser Ser Glu395039553960Phe Val Glu His Ser Gly Pro Asp Ser Glu Ser Ala Val Asn Val396539703975Pro Val Val Pro Trp Val Val Ser Gly Lys Thr Pro Glu Ala Leu398039853990Ser Ala Gln Ala Asp Thr Leu Val Ser Tyr Leu Asp Asp Arg Ser399540004005Asp Val Ser Ser Arg Asp Val Gly Tyr Ser Leu Ala Met Thr Arg401040154020Ser Ala Leu Asp Glu Arg Ala Val Val Leu Gly Ser Asp Arg Glu402540304035Thr Leu Leu Ser Gly Leu Lys Ala Leu Ala Ala Gly His Glu Ala404040454050Thr Gly Val Val Thr Gly Ser Val Gly Ser Gly Gly Arg Pro Gly405540604065Phe Val Phe Ala Gly Gln Gly Gly Gln Trp Leu Gly Met Gly Arg407040754080Gly Leu Tyr Arg Ala Phe Pro Val Phe Ala Asp Ala Phe Asp Glu408540904095Ala Cys Ala Gly Leu Asp Ala His Leu Gly Gln Glu Val Gly Val410041054110Arg Asp Val Val Phe Gly Ser Asp Ala Gln Leu Leu Asp Arg Thr411541204125Leu Trp Ala Gln Ser Gly Leu Phe Ala Leu Gln Val Gly Leu Leu413041354140Lys Leu Leu Gly Ser Trp Gly Val Arg Pro Val Val Val Leu Gly414541504155His Ser Val Gly Glu Leu Ala Ala Ala Phe Ala Ala Gly Val Leu416041654170Ser Met Ala Glu Ala Ala Arg Leu Val Ala Gly Arg Ala Arg Leu417541804185Met Gln Ala Leu Pro Ser Gly Gly Ala Met Leu Ala Val Ala Ala
419041954200Thr Glu Asp Arg Ile Ser Pro Leu Leu Asp Gly Val Arg Asp Arg420542104215Val Gly Val Ala Ala Val Asn Ala Pro Gly Ser Ala Val Leu Ser422042254230Gly His Arg Asp Val Leu Glu Asp Val Val Gly Arg Leu Asp Gly423542404245Leu Gly Val Arg Trp Arg Trp Leu Arg Val Ser His Ala Phe His425042554260Ser Tyr Arg Met Asp Pro Met Leu Asp Glu Phe Ala Asp Ile Ala426542704275Arg Ser Val Asp Tyr Arg Ser Pro Gly Leu Pro Ile Val Ser Thr428042854290Leu Thr Gly Asn Leu Asp Asp Val Gly Val Met Ala Thr Pro Glu429543004305Tyr Trp Val Arg Gln Val Arg Glu Pro Val Arg Phe Ala Asp Gly431043154320Val Gln Ala Leu Val Asn Gln Gly Val Asp Thr Ile Val Glu Leu432543304335Gly Pro Asp Gly Val Leu Ser Ser Leu Val His Glu Cys Val Ser434043454350Glu Ser Gly Arg Val Thr Gly Ile Pro Leu Val Arg Lys Asp Arg435543604365Asp Glu Val Pro Thr Val Leu Ala Ala Leu Ala Gln Ile His Thr437043754380Arg Gly Gly Ala Val Asp Trp Gly Ser Phe Phe Ala Gly Thr Gly438543904395Ala Lys Gln Val Glu Leu Pro Thr Tyr Ala Phe Gln Arg Arg Arg440044054410Tyr Trp Leu Glu Pro Ser Asp Ser Gly Asp Val Thr Gly Ala Gly441544204425Leu Thr Gly Ala Glu His Pro Leu Leu Gly Ala Val Val pro Val443044354440Ala Gly Ala Asp Glu Val Leu Leu Thr Gly Arg Leu Ser Val Gly444544504455Thr His Pro Trp Leu Ala Asp His Arg Val Leu Gly Glu Val Val446044654470Val Pro Gly Thr Ala Leu Leu Glu Met Ala Trp Arg Ala Gly Ser447544804485Gln Val Gly Cys Glu Arg Val Glu Glu Leu Thr Leu Glu Ala Pro
449044954500Leu Val Leu Pro Glu Arg Gly Ala Ala Ala Val Gln Leu Ala Val450545l04515Gly Ala Pro Asp Glu Ala Gly Arg Arg Ser Leu Gln Leu Tyr Ser452045254530Arg Gly Ala Asp Glu Asp Gly Asp Trp Arg Arg Ile Ala Ser Gly453545404545Leu Leu Ala Gln Ala Ser Val Val Pro Pro Ala Asp Ser Thr Ala455045554560Trp Pro Pro Asp Gly Ala Val Gln Val Asp Leu Ala Glu Phe Tyr456545704575Glu Arg Leu Ala Glu Arg Gly Leu Thr Tyr Gly Pro Val Phe Gln458045854590Gly Leu Arg Ala Ala Trp Arg Tyr Gly Asp Asp Ile Phe Ala Glu459546004605Leu Ala Val Ser Pro Asp Ala Ala Gly Phe Gly Ile His Pro Ala461046l54620Leu Leu Asp Ala Ala Leu His Ala Met Ala Leu Gly Ala Ser Pro462546304635Asp Ser Glu Ala Arg Leu Pro Phe Ser Trp Ser Gly Ala Gln Leu464046454650Tyr Arg Ala Gly Gly Ala Ala Leu Arg Val Arg Leu Ser Pro Leu465546604665Gly Thr Gly Ala Val Ser Leu Thr Leu Met Asp Ala Ala Gly Gly467046754680Gln Val Ala Ala Val Glu Ser Leu Ser Thr Arg Pro Val Ser Ala468546904695Asp Gln Ile Gly Ala Gly Arg Gly Asp His Glu Arg Leu Leu His470047054710Val Glu Trp Val Arg Pro Ala Glu Ser Ala Gly Met Ser Leu Thr471547204725Ser Cys Ala Val Val Gly Leu Asp Glu Pro Glu Trp His Ala Ala473047354740Leu Lys Ala Thr Gly Val Gln Val Glu Ser His Ala Asp Leu Ala474547504755Ser Leu Ala Thr Glu Val Ala Lys Arg Gly Ser Ala Pro Gly Ala476047654770Val Ile Val Pro Cys Pro Arg Pro Gln Ala Met Glu Glu Leu Pro477547804785Thr Ala Ala Arg Arg Ala Thr Gln Gln Ala Met Ala Leu Leu Gln
479047954800Glu Trp Leu Ala Asp Asp Arg Phe Val Ser Thr Arg Leu Ile Leu480548104815Leu Thr His Arg Ala Val Ala Ala Val Ala Gly Glu Asp Val Phe482048254830Asp Leu Val His Ala Pro Leu Trp Gly Leu Val Arg Ser Ala Gln483548404845Ala Glu His Pro Asp Arg Phe Ala Leu Ile Asp Val Asp Glu Ala485048554860Glu Ala Ser Arg Ala Ala Leu Ala Glu Ala Leu Thr Ala Gly Glu486548704875Ala Gln Leu Ala Val Arg Ser Gly Val Val Leu Val Pro Arg Leu488048854890Gly Gln Val Lys Ala Ser Gly Gly Glu Ala Phe Arg Trp Asp Glu489549004905Gly Thr Val Leu Val Thr Gly Gly Thr Gly Gly Leu Gly Ala Leu491049154920Leu Ala Arg His Leu Val Ser Ala His Gly Val Arg His Leu Leu492549304935Leu Ala Ser Arg Arg Gly Leu Ala Ala Pro Gly Ala Asp Glu Leu494049454950Val Ala Glu Leu Glu Gln Ser Gly Ala Asp Val Ala Val Val Ala495549604965Cys Asp Ala Ala Asp Arg Asp Ser Leu Ala Arg Leu Val Ala Ser497049754980Val Pro Ala Glu Asn Pro Leu Arg Ala Val Val His Ala Ala Gly498549904995Val Leu Asp Asp Gly Val Leu Met Ser Met Ser Pro Glu Arg Leu500050055010Asp Ala Val Leu Arg Ser Lys Val Asp Ala Ala Trp Tyr Leu His501550205025Glu Leu Thr Arg Glu Leu Gly Leu Ser Ala Phe Val Leu Phe Ser503050355040Ser Val Ala Gly Leu Leu Gly Gly Ala Gly Gln Ser Asn Tyr Ala504550505055Ala Gly Asn Ala Phe Leu Asp Ala Leu Ala His Cys Arg Gln Ala506050655070Gln Gly Leu Pro Ala Leu Ser Leu Ala Ser Gly Leu Trp Ala Ser507550805085Ile Asp Gly Met Ala Gly Asp Leu Ala Ala Ala Asp Val Glu Arg
509050955l00Leu Ser Arg Ala Gly Ile Ala Pro Leu Ser Ala Pro Gly Gly Leu510551105115Ala Leu Phe Asp Ala Ala Ile Arg Ser Asp Glu Pro Leu Leu Ala512051255130Pro Val Arg Leu Asp Val Glu Ala Leu Arg Val Gln Ala Arg Ser513551405145Ala Glu Thr Arg Ile Pro Glu Met Leu His Gly Met Ala Met Gly515051555160Pro Ser Arg Arg Thr Ser Phe Ser Ser Arg Val Glu Pro Leu Gln516551705175Glu Arg Leu Ala Gly Leu Ser Glu Asp Glu Arg Arg Gln Gln Val518051855190Leu Gln Arg Val Arg Ala Asp Ile Ala Val Val Leu Gly His Gly519552005205Lys Ser Asn Asp Val Asp Thr Glu Lys Pro Leu Ala Glu Leu Gly521052155220Phe Asp Ser Leu Thr Ala Ile Glu Leu Arg Asn Arg Leu Ala Thr522552305235Ala Thr Gly Leu Arg Leu Pro Ala Thr Leu Ala Phe Asp His Gly524052455250Thr Ala Ala Ala Leu Ala Trp His Val Cys Ala Gln Leu Gly Thr525552605265Ala Thr Val Pro Ala Pro Arg Arg Thr Asp Asp Asn Asp Ser Ala527052755280Glu Pro Val Arg Ser Leu Phe Gln Gln Ala Tyr Ala Ala Gly Arg528552905295Ile Leu Asp Gly Met Asp Leu Val Lys Val Ala Ala Gln Leu Arg530053055310Pro Val Phe Gly Ser Pro Gly Glu Leu Glu Ser Leu Pro Lys Pro531553205325Val Gln Leu Ser Arg Gly Pro Lys Glu Pro Ala Leu Val Cys Met533053355340Pro Ala Leu Ile Gly Met Pro Pro Ala Gln Gln Tyr Ala Arg Ile534553505355Ala Ala Gly Phe Arg Asp Val Arg Asp Val Ser Val Val Pro Met536053655370pro Gly Phe Val Ala Gly Glu Pro Leu Pro Ser Ala Ile Glu Val537553805385Ala Val Arg Thr Gln Ala Glu Ala Val Leu Gln Glu Phe Ala Gly
539053955400Asp Ser Phe Val Leu Val Gly His Ser Ser Gly Gly Trp Leu Ala540554105415His Glu Val Ala Gly Val Leu Glu Arg Arg Gly Val Leu Pro Ala542054255430Gly Val Val Leu Leu Asp Thr Tyr Ile Pro Gly Glu Ile Thr Pro543554405445Arg Phe Ser Ala Ala Met Ala His Arg Thr Tyr Glu Lys Leu Ala545054555460Thr Phe Thr Asp Met Gln Asp Ile Ala Ile Thr Ala Met Gly Gly546554705475Tyr Phe Arg Met Phe Thr Glu Trp Thr Pro Thr Pro Ile Gly Thr548054855490Pro Thr Leu Phe Val Arg Thr Glu Asp Cys Val Ala Asp Pro Glu549555005505Gly Arg Pro Trp Thr Asp Asp Ser Trp Arg Pro Gly Trp Thr Leu55l055155520Ala Asp Ala Thr Val Gln Val Pro Gly Asp His Phe Ser Met Met552555305535Asp Glu His Ser Gly Ser Thr Ala Gln Ala Val Ala Ser Trp Leu554055455550Glu Lys Leu Ser Gln Arg Thr Ala Arg Gln Arg55555560<210>8<211>275<212>PRT<213>刺糖多胞菌NRRL30141<400>8Val Leu Pro Gly Gly Val Pro Thr Ser Gln Gln Val Gly Gln Met Tyr1 5 10 15Asp Leu Val Thr Pro Leu Leu Asn Ser Val Ala Gly Gly Pro Cys Ala20 25 30Ile His His Gly Tyr Trp Glu Asn Asp Gly Arg Thr Ser Trp Gln Gln35 40 45Ala Ala Asp Arg Leu Thr Asp Leu Val Ala Glu Arg Thr Ala Leu Asp50 55 60Gly Gly Asn Arg Leu Leu Asp Val Gly Cys Gly Thr Gly Gln Pro Ala65 70 75 80Leu Arg Val Ala Arg Asp Asn Ala Ile Arg Ile Thr Gly IIe Thr Val85 90 95
Ser Gln Val Gln Ala Ala Ile Ala Val Asp Cys Ala Arg Glu Arg Gly100 105 110Leu Ser His Gln Val Asp Phe Ser Cys Val Asp Ala Met Ssr Leu Pro115 120 125Tyr Pro Asp Asn Ala Phe Asp Ala Ala Trp Ala Ile Gln Ser Leu Leu130 135 140Glu Met Ser Glu Pro Asp Arg Ala Ile Arg Glu Ile Val Arg Val Leu145 150 155 160Lys Pro Gly Gly Ile Leu Gly Val Thr Glu Val Val Lys Arg Glu Ile165 170 175Gly Ser Gly Ile Pro Val Ser Trp Asp Met Trp Pro Thr Gly Leu Arg180 185 190Ile Cys Leu Ala Glu Gln Leu Leu Glu Ser Leu Cys Ala Ala Gly Phe195 200 205Glu Ile Leu Ala Cys Asp Asp Val Ser Ser Arg Thr Arg Tyr Phe Met210 215 220Pro Gln Phe Ala Glu Ala Leu Ala Ala His Gln His Gly Ile Ala Glu225 230 235 240Arg Tyr Gly Pro Ala Val Ala Asp Trp Ala Ala Ala Val Cys Asp Tyr245 250 255Glu Lys Tyr Ala Asp Asp Met Gly Tyr Ala Ile Leu Thr Ala Arg Lys260 265 270Pro Val Gly275<210>9<2ll>390<212>PRT<213>刺糖多胞菌NRRL30141<400>9Met Arg Val Leu Val Val Pro Leu Pro Tyr Pro Thr His Leu Met Ala15 10 15Met Val Pro Leu Cys Trp Ala Leu Arg Ala Ser Gly His Glu Val Leu20 25 30Val Ala Ala Pro Pro Glu Leu Gln Ala Thr Ala His Gly Ala Gly Leu35 40 45Thr Thr Ala Glu Ile Arg Gly Asn Asp Lys Thr Arg Asp Thr Gly Ser50 55 60Thr Thr Arg Leu Arg Phe Pro Asn Pro Ala Phe Gly Gln Arg Asp Thr65 70 75 80Glu Thr Gly Arg Gln Leu Trp Glu Gln Thr Ala Ser Tyr Val Val Gln85 90 95
Ser Ser Leu Asp Gln Leu Pr0 Glu Tyr Leu Arg Leu Ala Glu Ala Trp100 105 110Arg Pro Ser Val Leu Leu Val Asp Val Cys Ala Leu Ile Gly Arg Val115 120 125Leu Gly Gly Leu Leu Asp Leu Pro Val Val Leu His Arg Trp Gly Val130 135 140Asp Pro Thr Ala Gly Pro Phe Ser Asp Arg Ala His Glu Leu Leu Asp145 150 155 160Pro Val Cys Arg His His Gly Leu Ala Gly Leu Pro Thr Pro Glu Leu165 170 175Ile Leu Asp Pro Cys Pro Pro Ser Leu Gln Ala Ser Asp Ala Pro Arg180 185 190Gly Val Pro Val Gln Tyr Val Pro Tyr Asn Gly Ser Gly Glu Leu Pro195 200 205Ala Trp Gly Ala Ala Arg Thr Ser Ala Arg Arg Val Cys Ile Cys Met210 215 220Gly Arg Met Val Leu Asn Ala Thr Gly Pro Ala Pro Leu Leu Arg Ala225 230 235 240Val Ala Ala Ala Thr Gly Leu Pro Gly Val Glu Ala Val Ile Ala Val245 250 255Pro Pro Glu His Arg Ala Leu Leu Thr Asp Leu Pro Asp Asn Ala Arg260 265 270Ile Ala Glu Ser Val Pro Leu Asn Leu Phe Leu Arg Thr Cys Glu Leu275 280 285Val Ile Cys Ala Gly Gly Ser Gly Thr Ala Phe Thr Ala Thr Arg Leu290 295 300Gly Ile Pro Gln Leu Val Leu Pro Gln Tyr Phe Asp Gln Phe Asp Tyr305 310 315 320Ala Arg Asn Leu Thr Ala Ala Gly Ala Gly Ile Cys Leu Pro Asp Glu325 330 335Gln Ala Gln Ser Asp His Glu Gln Phe Thr Gly Ser Ile Ala Thr Val340 345 350Leu GLy Asp Thr Gly Phe Ala Ala Ala Ala Thr Lys Leu Ser Asp Glu355 360 365Ile Thr Ala Met Pro Asn Pro Ala Glu Leu Val Arg Thr Leu Glu Ser370 375 380Ser Ala AlaIle Gly Ala385390<210>10
<211>250<212>PRT<213>刺糖多胞菌NRRL30141<400>10Met Pro Ser Gln Asn Ala Leu Tyr Leu Asp Leu Leu Lys Lys Val Leu1 5 10 15Thr Asn Thr Ile Tyr Gly Asp Arg Pro His Thr Asn Val Trp Gln Asp20 25 30Asn Thr Asp Tyr Arg Gln Ala Ala Arg Ala Lys Gly Thr Asp Trp Pro35 40 45Thr Val Ala His Thr Met Ile Gly Leu Glu Arg Leu Asp Asn Leu Gln50 55 60His Cys Val Glu Ala Val Leu Ala Asp Gly Val Pro Gly Asp Phe Ala65 70 75 80Glu Thr Gly Val Trp Arg Gly Gly Ala Cys Ile Phe Met Arg Ala Val85 90 95Leu Gln Ala Phe Gly Asp Thr Gly Arg Thr Val Trp Val Val Asp Ser100 105 110Phe Gln Gly Met Pro Glu Ser Ser Ala Gln Asp His Glu Ser Asp Gln115 120 125Ala Met Ala Leu His Glu Tyr Asn Asp Val Leu Gly Val Pro Leu Glu130 135 140Thr Val Arg Gln Asn Phe Ala Arg Tyr Gly Leu Leu Asp Glu Gln Val145 150 155 160Arg Phe Leu Pro Gly Trp Phe Arg Asp Thr Leu Pro Thr Ala Pro Ile165 170 175Gln Glu Leu Ala Val Leu Arg Leu Asp Gly Asp Leu Tyr Glu Ser Thr180 185 190Met Asp Ser Leu Arg Asn Leu Tyr Pro Lys Leu Ser Pro Gly Gly Phe195 200 205Val Ile Ile Asp Asp Tyr Val Leu Pro Ser Cys Gln Asp Ala Val Lys2l0 215 220Gly Phe Arg Ala Glu Leu Gly Ile Thr Glu Pro Ile His Asp Ile Asp225 230 235 240Gly Thr Gly Ala Tyr Trp Arg Arg Ser Trp245 250<210>11<211>395<212>PRT<213>刺糖多胞菌NRRL30141<400>11
Met Gly Glu Ile Ala Val Ala Pro Trp Ser Val Val Glu His Leu Leu1 5 10 15Leu Ala Ala Gly Ala Gly Thr Glu Arg Leu Gln Glu Ala Val Gln Val20 25 30Ala Gly Leu Glu Ala Val Ala Asp Ala Ile Val Asp Glu Leu Val Val35 40 45Arg Cys Asp Pro Leu Ser Leu Asp Glu Ser Val Arg Ile Gly Leu Glu50 55 60Ile Thr Ser Gly Ala Gln Leu Val Arg Arg Thr Val Glu Leu Asp His65 70 75 80Ala Gly Leu Arg Leu Ala Ala Val Ala Glu Ala Pro Ala Val Leu Arg85 90 95Phe Asp Ala Val Asp Leu Leu Glu GIy Leu Phe Gly Pro Val Asp Gly100 105 110Arg Arg His Asn Ser Arg Glu Val Arg Trp Ser Asp Ser Met Thr Gln115 120 125Phe Ser Pro Asp Gln Gly Leu Ala Gly Ala Gln Arg Leu Leu Ala Phe130 135 140Arg Asn Lys Val Ser Thr Ala Val His Ala Val Leu Ala Ala Ala Ala145 150 155 160Thr Arg Cys Ser Asp Leu Gly Glu Leu Ala Val Arg Tyr Gly Ser Asp165 170 175Lys Trp Ala Asp Leu His Trp Tyr Thr Glu His Tyr Glu His His Phe180 185 190Ser Arg Phe Gln Asp Val Pro Val Arg Val Leu Glu Ile Gly Ile Gly195 200 205Gly Tyr His Ala Pro Glu Leu Gly Gly Ala Ser Leu Arg Met Trp Gln210 215 220Arg Tyr Phe Arg Arg Gly Leu Val Tyr Gly Leu Asp Ile Phe Glu Lys225 230 235 240Ala Gly Asn Glu Gly His Arg Val Arg Lys Leu Arg Gly Asp Gln Ser245 250 255Asp Ala Glu Phe Leu Ala Asp Met Ala Gly Lys Ile Gly Pro Phe Asp260 265 270Ile Val Ile Asp Asp Gly Ser His Val Asn Asp His Val Lys Lys Ser275 280 285Phe His Ala Leu Phe Pro His Val Arg Pro Gly Gly Leu Tyr Val Ile290 295 300Glu Asp Leu Gln Thr Ser Tyr Trp Pro Gly Tyr Gly Gly Arg Asp Thr305 310 315 320
Glu Pro Ala Ala Gln Arg Thr Ser Ile Asp Met Leu Lys Glu Leu Ile325 330 335Asp Gly Leu His Tyr Gln Glu Arg Glu Ser Arg Arg Gly Thr Glu Pro340 345 350Cys Tyr Thr Glu Arg Asn Val Ala Ala Leu His Phe Tyr His Asn Leu355 360 365Val Phe Val Glu Lys Gly Leu Asn Ala Glu Pro Ala Ala Pro Gly Phe370 375 380Val Pro Arg Gln Ala Leu Gly Val Glu Asp Ser385 390 395<210>12<211>539<212>PRT<213>刺糖多胞菌NRRL30141<400>12Met Ile Ser Ala Glu Gly Glu Gln Ser Gly Pro Val Ser Lys Gly Gly1 5 10 15Ala Val Pro Asp Phe His Asp Pro Ala Thr Met Asn Arg Arg Thr Pro20 25 30Gly Thr Glu Ile Thr Val Glu Pro Gly Asp Pro Arg Tyr Pro Asp Leu35 40 45Val Val Gly His Asn Pro Arg Phe Thr Gly Lys Pro Glu Arg Ile His50 55 60Ile Ala Gly Ser Thr Glu Asp Val Val His Ala Val Ala Glu Ala Val65 70 75 80Arg Thr Gly Arg Arg Val Gly Val Arg Ser Gly Gly His Cys Phe Glu85 90 95Asn Leu Val Ala Asp Pro Ala Ile Arg Val Leu Val Asp Leu Ser Glu100 105 110Leu Asr Arg Val Tyr Phe Asp Ser Thr Arg Gly Ala Phe Ala Ile Glu115 120 125Ala Gly Ala Ala Leu Gly Gln Val Tyr Arg Thr Leu Phe Lys Asn Trp130 135 140Gly Val Thr Ile Pro Thr Gly Ala Cys Pro Gly Val Gly Ala Gly Gly145 150 155 160His Ile Pro Gly Gly Gly Tyr Gly Pro Leu Ser Arg Arg Phe Gly Ser165 170 175Val Val Asp Tyr Leu Gln Gly Val Glu Val Val Val Val Asp Arg Ala180 185 190Gly Glu Val His Ile Val Glu Val Asp Arg Asn Ser Ile Gly Ala Gly195 200205
His Asp Leu Trp Trp Ala His Thr Gly Gly Gly Gly Gly Asn Phe Gly210 215 220Val Val Thr Arg Phe Trp Leu Arg Ala Pro Asp Val Val Ser Thr Asp225 230 235240Pro Ser Glu Leu Leu Pro Arg Pro Pro Ala Thr Val Leu Leu Arg Ser245 250 255Phe His Trp Pro Trp Cys Glu Leu Thr Glu Gln Ser Phe Ala Leu Leu260 265 270Leu Arg Asn Phe Gly Thr Trp Tyr Glu Gln His Ser Ala Pro Glu Ser275 280 285Thr Gln Leu Gly Leu Phe Ser Thr Leu Val Cys Ala His Arg Gln Ala290 295 300Gly Tyr Val Thr Leu Asn Ile His Leu Asp Gly Thr Asp Pro Asn Ala305 310 315 320Glu Arg Thr Leu Ala Glu His Leu Ser Ala Ile Asn Asp Gln Val Gly325 330 335Val Thr Pro Ala Glu Gly Leu Arg Glu Thr Leu Pro Trp Leu Arg Ser340 345 350Thr Gln Val Ser Gly Ser Leu Ala Glu Gly Gly Glu Pro Ser Gly Gln355 360 365Arg Thr Lys Val Lys Ala Ala Tyr Leu Arg Thr Gly Leu Ser Glu Ala370 375 380Gln Leu Ala Thr Val Tyr Arg Arg Leu Thr Asp Ser Gly Tyr Asp Asn385 390 395 400Pro Ala Ala Ala Leu Leu Leu Leu Gly Tyr Gly Gly Arg Ala Asn Ala405 410 415Val Ala Pro Ser Ala Thr Ala Leu Ala Gln Arg Asp Ser Val Leu Lys420 425 430Ala Leu Phe Val Thr Asn Trp Ser Glu Pro Ala Glu Asp Glu Arg His435 440 445Leu Thr Trp Ile Arg Gly Phe Tyr Arg Glu Met Tyr Ala Glu Thr Gly450 455 460Gly Val Pro Val Pro Gly Thr Arg Val Asp Gly Ser Tyr Ile Asr Tyr465 470 475 480Pro Asp Thr Asp Leu Ala Asp Pro Leu Trp Asn Thr Ser Gly Val Ala485 490 495Trp His Asp Leu Tyr Tyr Lys Asp Asn Tyr Pro Arg Leu Gln Arg Ala500 505 510Lys Ala Arg Trp Asp Pro Gln Asn Ile Phe Gln His Gly Leu Ser Ile515 520 525
Lys Pro Pro Glu Arg Leu Ser Pro Gly Gln Pro530 535<210>13<211>397<212>PRT<213>刺糖多胞菌NRRL30141<400>13Met Ser Ala Thr His Glu Ile Glu Thr Val Glu Arg Ile Ile Leu Ala1 5 10 15Ala Gly Ser Ser Ala Ala Ser Leu Ala Glu Leu Thr Thr Glu Leu Gly20 25 30Leu Ala Arg Ile Ala Pro Val Leu Ile Glu Glu Ile Leu Phe Arg Ala35 40 45Glu Pro Ala Pro Asp Ile Glu Pro Thr Glu Val Ala Val Gln Ile Thr50 55 60His Gly Val Glu Thr Val Asp Phe Val Leu Lys Leu Gln Ser Gly Glu65 70 75 80Leu Ile Lys Ala Glu Gln Arg Pro Val Gly Asp Val Pro Leu Arg Ile85 90 95Gly Tyr Glu Leu Thr Asp Leu Ile Ala Glu Leu Phe Gly Pro Gly Ala100 105 110Pro Arg Ala Val Gly Ala Arg Ser Thr Asi Phe Leu Arg Thr Thr Thr115 120 125Ser Gly Ser Ile Pro Gly Pro Ser Glu Leu Ser Asp Gly Phe Gln Ala130 135 140Ile Ser Ala Val Val Ala Gly Cys Gly His Arg Arg Pro Asp Leu Asp145 150 155 160Gln Leu Ala Ser His Tyr Arg Thr Asp Lys Trp Gly Gly Leu His Trp165 170 175Phe Thr Pro Leu Tyr Glu Arg His Leu Gly Glu Phe Arg Asp Arg Pro180 185 190Val Arg Ile Leu Glu Ile Gly Val Gly Gly Tyr Asn Phe Asp Gly Gly195 200 205Gly Gly Glu Ser Leu Lys Met Trp Lys Arg Tyr Phe His Arg Gly Leu210 215 220Val Phe Gly Met Asp Val Phe Asp Lys Ser Phe Leu Asp Gln Gln Arg225 230 235 240Leu Tyr Thr Val Arg Ala Asp Gln Ser Lys Pro Glu Glu Leu Ala Ala245 250 255Val Asp Asp Glu Tyr Gly Pro Phe Asp Ile Ile Ile Asp Asp Gly Ser
260 265 270His Ile Asn Gly His Val Arg Thr Ser Leu Glu Thr Leu Phe Pro Arg275 280 285Leu Arg Ser Gly Gly Val Tyr Val Ile Glu Asp Leu Trp Thr Thr Tyr290 295 300Ala Pro Gly Phe Gly Gly Gln Ala Gln Ser Pro Ala Ala Pro Gly Thr305 310 315 320Thr Val Ser Leu Leu Lys Asn Leu Leu Glu Gly Val Gln His Glu Glu325 330 335Gln Pro His Ala Gly Ser Tyr Glu Pro Ser Tyr Leu Glu Arg Asn Val340 345 350Val Gly Leu His Val Tyr His Asn Ile Ala Phe Leu Glu Lys Gly Val355 360 365Asn Ala Glu Gly Ala Val Pro Ala Trp Val Pro Arg Ser Leu Asp Asp370 375 380Ile Leu His Leu Ala Asp Val Asn Ser Ala Glu Asp Lys385 390 395<210>14<211>283<212>PRT<213>刺糖多胞菌NRRL30141<400>14Val Glu Ser Ile Phe Asp Ala Leu Ala Gln Gly Arg Ala Leu His His1 5 10 15Gly Tyr Trp Ala Gly Gly Tyr Arg Glu Asp Ala Gly Ala Thr Pro Trp20 25 30Ser Asp Ala Ala Asp His Leu Thr Asp Leu Phe Ile Asp Lys Ala Ala35 40 45Leu Arg Pro Gly Ala His Leu Phe Asp Leu Gly Cys Gly Asn Gly Gln50 55 60Pro Val Val Arg Ala Ala Arg Thr Lys Gly Val Arg Val Thr Gly Ile65 70 75 80Thr Val Asn Ala Glu His Leu Ala Ala Ala Thr Arg Leu Ala Asn Glu85 90 95Thr Gly Leu Ala Asp Ser Leu Arg Phe ASp Leu Val Asp Gly Ala Arg100 105 110Leu Pro Tyr Pro Glu Gly Ser Phe His Ala Ala Trp Ala Met Gln Ser115 120 125Val Val Gln Ile Val Asp Gln Ala Ala Ala Ile Arg Glu Val His Arg130 135 140
Ile Leu Glu Pro Gly Gly Gln Phe Val Leu Gly Asp Ile Ile Thr Arg145 150 155 160Ala Arg Leu Pro Glu Glu Tyr Ala Ala Val Trp Thr Gly Thr Thr Ala165 170 175His Thr Leu Asn Ser Leu Thr Ala Leu Val Ser Glu Ala Gly Phe Glu180 185 190Ile Leu Glu Val Thr Asp Leu Thr Ala Gln Thr Arg Cys Met Val Ser195 200 205Trp Tyr Val Asp Glu Leu Leu Arg Glu Leu Asp Glu Leu Ala Gly Val210 215 220Glu Pro Ala Ala Val Gly Thr Tyr Gln Gln Arg Tyr Leu Gly Asp Ile225 230 235 240Ala Ala Lys His Gly Pro Gly Pro Ala Gln Leu Ile Ala Ala Val Ala245 250 255Glu Tyr Arg Lys His Pro Asp Tyr Ala Arg Asn Glu Glu Ser Met Gly260 265 270Phe Met Leu Leu Gln Ala Arg Lys Lys Gln Ser275 280<210>15<211>310<212>PRT<213>刺糖多胞菌NRRL30141<400>15Val Pro Asn Ile Pro Trp Pro Gly Glu Asp Arg Pro Ile Ile Thr Phe1 5 10 15Ala Val Gly Thr His Gly Leu Gly Ser Gln Val Ala Pro Ser Tyr Leu20 25 30Leu Arg Thr Gly Thr Glu Pro Glu Thr Glu Leu Ile Ala Val Ala Leu35 40 45Asp Arg Gly Trp Ala Val Val Ile Thr Asp Tyr Glu Gly Leu Gly Thr50 55 60Pro Gly Thr His Thr Tyr Thr Val Gly Arg Pro Gln Gly His Ala Met65 70 75 80Leu Asp Ala Ala Arg Ala Ala Gln Arg Leu Pro Gly Ser Gly Leu Gly85 90 95Thr Asp Cys Pro Val Gly Ile Trp Gly Tyr Ala Gln Gly Gly Gln Ala100105 110Ser Ala Phe Ala Gly Glu Leu His Pro Thr Tyr Ala Pro Glu Leu Pro115 120 125Ile Arg Ala Ala Ala Ala Gly Ala Val Pro I1e Asp Leu Leu Asp Ile130 135 140
Leu His Arg Asn Asp Gly Val Phe Thr G1y Pro Val Leu A1a Gly Leu145 150 155 160Val Gly His Ala Ala Ala Tyr Pro Asp Leu Pro Phe Asp Glu Leu Leu165 170 175Thr Asp Ala Gly Arg I1e Ala Val Asp Gln Val Arg Glu Leu G1y Ala180185 190Pro Glu Leu Val Thr Arg Phe Leu Gly Arg Glu Leu Ser Asp Phe Leu195 200 205Asp Thr Ser Gly Leu Phe Glu His Pro Arg Trp Arg Ala Arg Leu Val210 215 220Glu Ser Val Ala Gly Arg Asn Gly Gly Pro Val Val Pro Thr Leu Val225 230 235 240Tyr His Ser Thr Asp Asp Glu Ile Val Pro Phe Ala Phe Gly Glu Arg245 250 255Leu Arg Asp Ser Tyr Arg Ala Ala Gly Thr Pro Val Arg Trp His Pro260 265 270Leu Ser Gly Leu Ala His Phe Pro Ala Ala Leu Ala Ser Ser Arg Val275 280 285Val Val Ser Trp Phe Asp Glu His Phe Ser Gly Pro Ser Ala Ile Ser290 295 300Gly Pro Arg Asp Asp Gly305 310<210>16<211>332<212>PRT<213>刺糖多胞菌NRRL30141<400>16Met Arg Lys Pro Val Arg 1le Gly Val Leu Gly Cys Ala Ser Phe Ala1 5 10 15Trp Arg Arg Met Leu Pro Ala Met Cys Asp Val Ala Glu Thr Glu Val20 25 30Val Ala Val Ala Ser Arg His Pro Ala Lys Ala Glu Arg Phe Ala Ala35 40 45Arg Phe Glu Cys Glu Ala Val Leu Gly Tyr Gln Arg Leu Leu Glu Arg50 55 60Pro Asp Ile Asp Ala Val Tyr Val Pro Leu Pro Pro Gly Met His Ala65 70 75 80Glu Trp Ile Gly Lys Ala Leu Glu Ala Gly Lys His Val Leu Ala Glu85 90 95Lys Pro Leu Thr Thr Thr Ala Ser Glu Thr Ala Arg Leu Val Gly Leu
100 105 1l0Ala Arg Arg Lys His Leu Leu Leu Arg Glu Asn Tyr Leu Phe Leu His115 120 125His Gly Arg His Asp Val Val Arg Asp Leu Leu Gln Ser Glu Glu Ile130 135 140Gly Glu Leu Arg Glu Phe Thr Ala Val Phe Gly Ile Pro Pro Leu Ser145 150 155 160Asp Thr Asp Ile Arg Tyr Arg Thr Glu Leu Gly Gly Gly Ala Leu Leu165 170 175Asp Ile Gly Val Tyr Pro Ala Arg Ala Ala Arg Leu Phe Leu Leu Gly180 185 190Pro Leu Thr Val Ala Gly Ala Ser Ser His Glu Ala His Glu Ser Gly195 200 205Val Asp Leu Ser Gly Ser Val Leu Leu Gln Ser Glu Gly Gly Ala Val210 215 220Ala His Leu Gly Tyr Gly Phe Val His His Tyr Arg Ser Ala Tyr Glu225 230 235 240Leu Trp Gly Ser Arg Gly Arg Ile Val Ile Asp Arg Ala Phe Thr Pro245 250 255Pro Ala Glu Trp Gln Ala Val Ile Arg Ile Glu Arg Lys Gly Val Val260 265 270Asp Glu Leu Ser Leu Pro Ala Glu Asp Gln Val Arg Lys Ala Val Thr275 280 285Ala Phe Ala Arg Asp Ile Arg Ala Glu Ala Gly Val Asp Glu Pro Ala290 295 300Val Ala Gly Asp Ser Gly Glu Ser Met Ile Gln Gln Ala Ala Leu Val305 310 315 320Glu Ala Ile Gly Gln Ala Cys Arg Cys Gly Ser Thr325 330<210>17<21l>486<212>PRT<213>刺糖多胞菌NRRL30141<400>17Met Ser Ser Phe Ala Glu Ala Glu Ala Ser Ala Ala Ala Pro Leu Ser1 5 10 15Ser Asn Asn Thr Arg Arg Phe Val Asp Ser Ala Leu Ser Ala Cys Asn20 25 30Gly Arg Phe Pro Thr Thr Arg Phe His Cys Trp Leu Ala Asp Arg Leu35 40 45
Gly Glu Asn Ser Phe Glu Thr Thr Arg Ile Pro Phe Asp Arg Leu Ser50 55 60Lys Trp Lys Phe Asp Ala Ser Thr Glu Asn Leu Val His Ala Asp Gly65 70 75 80Arg Phe Phe Thr Val Glu Gly Leu Gln Val Glu Thr Asn Tyr Gly Ala85 90 95Ala Thr Cys Trp His Gln Pro Ile Ile Asn Gln Ala Glu Val Gly Ile100 105 110Leu Gly Ile Leu Val Lys Glu Ile Asp Gly Val Leu His Cys Leu Met115 120 125Ser Ala Lys Met Glu Pro Gly Asn Val Asn Val Leu Gln Leu Ser Pro130 135 140Thr Val Gln Ala Thr Arg Ser Asn Tyr Thr Gln Ala His Arg Gly Ser145 150 155 160Val Pro Pro Tyr Val Asp Tyr Phe Leu Gly Arg Gly Arg Ser Arg Val165 170 175Leu Val Asp Val Leu Gln Ser Glu Gln Gly Ala Trp Phe Tyr Arg Lys180 185 190Arg Asn Arg Asn Met Val Val Glu Val Asp Glu Glu Val Pro Val Leu195 200 205Pro Asp Phe Cys Trp Leu Thr Leu Gly Gln Val Leu Asp Leu Leu Arg210 215 220Gln Asp Asn Ile Val Asn Met Asp Thr Arg Thr Val Leu Ser Cys Ile225 230 235 240Pro Phe His Asp Ser Ala Thr Gly Pro Gly Leu Ala Ala Ser Ala Glu245 250 255Pro Phe Arg Gln Ala Val Ala Arg Ser Leu Ser His GLy Ile Asp Ser260 265 270Ala Ser Ile Thr Glu Ala Val Gly Trp Phe Glu Glu Ala Lys Ala Arg275 280 285Tyr Ser Leu Arg Ala Thr Arg Val Pro Leu Ser Arg Val Asp Lys Trp290 295 300Tyr Arg Thr Asp Thr Glu Ile Ala His Gln Asp Gly Lys Tyr Phe Ser305 310 315 320Val Ile Ala Val Ser Val Ser Ala Thr Asn Arg Glu Val Ser Ser Trp325 330 335Thr Gln Pro Met Ile Glu Pro Arg Glu Pro Gly Glu Ile Ala Leu Leu340 345 350Val Lys Arg Ile Gly Gly Val Leu His Gly Leu Val Arg Ala Arg Val355 360 365
Glu Ala Gly Tyr Lys Ser Thr Ala Glu Ile Ala Pro Thr Val Gln Cys370 375 380Ser Val Ala Asu Tyr Gln Ser Thr Pro Arg Asn Asp Trp Pro Pro Phe385 390 395 400Val Asp Asp Val Leu Thr Ala Asp Pro Glu Thr Val Arg Tyr Glu Ser405 410 415Ile Leu Ser Glu Glu Gly Gly Arg Phe Tyr Gln Ala Gln Asn Arg Tyr420 425 430Arg Ile Ile Glu Val His Glu Asp Phe Ala Ala Arg Pro Pro Ser Asp435 440 445Phe Arg Trp Met Thr Leu Gly Gln Leu Gly Glu Leu Leu Arg Ser Thr450 455 460His Ser Leu Asn Ile Gln Ala Arg Ser Leu Val Ala Ser Leu His Ser465 470 475 480Leu Trp Ala Leu Gly Arg485<210>18<211>437<212>PRT<213>刺糖多胞菌NRRL30141<400>18Met Arg Val Leu Phe Thr Pro Leu Pro Ala Ser Ser His Phe Phe Asn1 5 10 15Leu Val Pro Leu Ala Trp Ala Leu Arg Ala Ala Gly His Glu Val Arg20 25 30Val Ala Ile Cys Pro Asn Met Val Ser Met Val Thr Gly Ala Gly Leu35 40 45Thr Ala Val Pro Val Gly Asp Glu Leu Asp Leu Ile Ser Leu Ala Ala50 55 60Arg Asn Lys Leu Val Leu Gly Asn Gly Val Ala Phe Asp Glu Gly Arg65 70 75 80Arg Pro Glu Leu Phe Asp Glu Leu Leu Ser Ile Asn Ser Gly Arg Asp85 90 95Met Asp Ala Val Glu Gln Leu His Leu Val Asp Asp Arg Ser Leu Asp100 105 110Asp Leu Met Gly Phe Ala Glu Lys Trp Gln Pro Asp Leu Val Val Trp115 120 125Asp Ala Met Val Cys Ser Gly Pro Val Val Ala Gln Ala Leu Gly Val130 135 140Arg His Val Arg Met Leu Val Ala Leu Asp Val Ser Gly Trp Leu Arg145 150 155 160
Ser Gly Phe Leu Glu Tyr Leu Glu Ser Lys Pro Pro Glu Gln Arg Val165 170 175Asp Pro Leu Gly Ala Trp Leu Gly Ala Lys Leu Ser Lys Phe Gly Ala180 185 190Thr Phe Asp Glu Glu Ile Val Thr Gly Gln Ala Thr Ile Asp Pro Val195 200 205Ser Ser Trp Met Arg Leu Pro Val Asp Leu Asp Tyr Ile Ser Met Arg210 215 220Phe Val Pro Tyr Asn Gly Pro Ala Val Val Pro Glu Trp Leu Arg Glu225 230 235 240Pro Pro Thr Lys Pro Arg Val Cys Val Thr Arg Gly Leu Thr Lys Arg245 250 255Gln Gln Ser Arg Val Ala Glu Gln Trp Glu Gly Glu Ala Gln Glu Gln260 265 270Ala Met Val Glu Thr Leu Leu Arg Gly Ala Ala Gly Leu Asp Val Glu275 280 285Val Ile Ala Thr Leu Ser Gly Gly Glu Val Arg Glu Met Gly Glu Leu290 295 300Pro Pro Asn Val Arg Val His Glu Tyr Val Pro Leu Asn Glu Leu Leu305 3l0 315 320Glu Ser Cys Ser Ala Ile Ile His His Gly Ser Thr Thr Thr Gln Glu325 330 335Thr Ala Thr Val Asn Gly Val Pro Gln Leu Ile Leu Pro Gly Thr Phe340 345 350Trp Asp Glu Ser Arg Arg Ala Glu Leu Leu Ala Asp Arg Gly Ala Gly355 360 365Leu Val Leu Asp Arg Ala Thr Phe Thr Glu Asp Asp Val Arg Arg Gln370 375 380Leu Ala Arg Leu Leu Asp Glu Pro Ser Phe Ala Ala Asn Ala Ala Leu385 390 395 400Ile Arg Gly Glu Ile Glu Glu Asn Pro Ser Pro His Asp Ile Val Ala405 410 415Arg Leu Glu Lys Leu Val Ala Glu Gly Lys Asn Arg Arg Ala Gly Lys420 425 430Ser Asp Gly His Leu435<210>19<211>447<212>PRT<213>刺糖多胞菌NRRL30141
<400>19Val Thr Ser Cys Asp Asp Thr Cys Ala Thr Ala Thr Glu Met Thr Pro1 5 10 15Asp Ala Lys Asp Arg Ile Leu Ala Ser Val Arg Asp Tyr His Arg Glu20 25 30Gln Lys Ser Ser Ile Phe Val Ala Gly Ser Thr Pro Ile Arg Pro Ser35 40 45Gly Ala Val Leu Asp Glu Asp Asp Arg Val Ala Leu Val Glu Ala Ala50 55 60Leu Glu Leu Arg Ile Ala Ala Gly Gly Asn Ala Arg Arg Phe Glu Ser65 70 75 80Glu Phe Ala Arg Phe Phe Gly Leu Arg Lyg Ala His Leu Thr Asn Ser85 90 95Gly Ser Ser Ala Asn Leu Leu Ala Leu Ser Ser Leu Thr Ser Pro Asn100 105 110Leu Gly Glu Ala Arg Leu Arg Pro Gly Asp Glu Val Ile Thr Ala Ala115 120 125Val Gly Phe Pro Thr Thr Ile Asn Pro Ala Val Gln Asn Gly Leu Val130 135 140Pro Val Phe Val Asp Val Glu Leu Gly Thr Tyr Asn Ala Thr Pro Asp145 150 155 160Arg Ile Lys Ala Ala Val Ser Glu Arg Thr Arg Ala Ile Met Leu Ala165 170 175His Thr Leu Gly Asn Pro Phe Ala Ala Asp Glu Ile Ala Glu Ile Ala180 185 190Arg Glu His Glu Leu Phe Leu Ile Glu Asp Asn Cys Asp Ala Val Gly195 200 205Ser Thr Tyr Arg Gly Arg Leu Thr Gly Thr Phe Gly Asp Leu Thr Thr210 215 220Val Ser Phe Tyr Pro Ala His His Ile Thr Ser Gly Glu Gly Gly Cys225 230 235 240Val Leu Thr Gly Ser Leu Glu Leu Ala Arg Ile Ile Glu Ser Leu Arg245 250 255Asp Trp Gly Arg Asp Cys Trp Cys Glu Pro Gly Val Asp Asn Thr Cys260 265 270Arg Lys Arg Phe Asp Tyr Gln Leu Gly Thr Leu Pro Ala Gly Tyr Asp275 280 285His Lys Tyr Thr Phe Ser His Val Gly Tyr Asn Leu Lys Thr Thr Asp290 295 300Leu Gln Ala Ala Leu Ala Leu Ser Gln Leu Ser Lys Ile Ser Glu Phe
305 310 315 320Gly Ser Ala Arg Arg Arg Asn Trp Arg Arg Leu Arg Glu Gly Leu Ser325 330 335Gly Val Pro Gly Leu Leu Leu Pro Val Pro Thr Pro His Ser Asp Pro340 345 350Ser Trp Phe Gly Phe Ala Ile Thr Val Ser Ala Asp Ala Gly Phe Thr355 360 365Arg Ala Ala Leu Val Asn Phe Leu Glu Ser Arg Asn Ile Gly Thr Arg370 375 380Leu Leu Phe Gly Gly Asn Ile Thr Arg His Pro Ala Phe Gln His Val385 390 395 400Arg Tyr Arg Ile Ala Asp Ala Leu Thr Asn Ser Asp Ile Val Thr Asp405 410 415Arg Thr Phe Trp Val Gly Val Tyr Pro Gly Ile Thr Asp Gln Met Ile420 425 430Asp Tyr Val Ala Glu Ser Ile Ala Glu Phe Val Ala Lys Asn Ser435 440 445<210>20<211>378<212>PRT<313>刺糖多胞菌NRRL30141<400>20Val Ile Asn Leu His Gln Pro Thr Leu Gly Ala Glu Glu Leu Asp Ala1 5 10 15Ile Ala Glu Val Phe Ala Ser Asn Trp Ile Gly Leu Gly Pro Arg Thr20 25 30Arg Thr Phe Glu Ala Asp Phe Ala His His Leu Gly Val Asp Pro Asp35 40 45Gln Ile Val Phe Val Agn Ser Gly Thr Ala Ala Leu Phe Leu Thr Val50 55 60Gln Val Leu Asp Leu Gly Pro Gly Asp Asp Val Val Leu Pro Ser Ile65 70 75 80Ser Phe Val Ala Ala Ala Asn Ala Ile Ala Ser Ser Gly Ala Arg Pro85 90 95Val Phe Cys Asp Val Asp Pro Arg Thr Leu Asn Pro Thr Leu Asp Asp100 105 110Val Ala Lys Ala Ile Thr Pro Thr Thr Lys Ala Val Leu Leu Leu His115 120 125Tyr Gly Gly Ser Pro Gly Glu Val Thr Glu Ile Ala Gly Phe Cys Arg130 135 140
Glu Lys Gly Leu Val Leu Ile Glu Asp Thr Ala Cys Ala Val Ala Ser145 150 155 160Ser Val His Gly Thr Ala Cys Gly Thr Phe Gly Asp Leu Ala Thr Trp165 170 175Ser Phe Asp Ala Met Lys Ile Leu Val Thr Gly Asp Gly Gly Met Phe180 185 190Tyr Ala Ala Asp Arg Glu Leu Ala His Arg Ala Arg Arg Leu Ala Tyr195 200 205His Gly Leu Glu Gln Met Ser Gly Phe Asp Ser Ala Lys Ser Ser Asn210 215 220Arg Trp Trp Asp Ile Cys Val Glu Asp Ile Gly His Arg Leu Ile Gly225 230 235 240Asn Asp Met Thr Ala Ala Leu Gly Ser Val Gln Leu Arg Lys Leu Pro245 250 255Asp Phe Val Ser Arg Arg Arg Glu Ile Ala Thr Gln Tyr Asp Arg Leu260 265 270Leu Ser Asp Val Pro Gly Val His Leu Pro Pro Thr Leu Pro Asp Gly275 280 285His Val Ser Ser His Tyr Phe Tyr Trp Val Gln Leu Ala Pro Glu Ile290 295 300Arg Asp Arg Val Ala Gln Gln Met Leu Glu Arg Gly Ile Tyr Thr Ser305 310 315 320Phe Arg Tyr Pro Pro Leu His Lys Val Pro Ile Tyr Arg Ala Asp Cys325 330 335Lys Leu Pro Ser Ala Glu His Ala Cys Arg Arg Thr Leu Leu Leu Pro340 345 350Leu His Pro Ser Leu Asp Asp Ala Glu Val Arg Thr Val Ala Asp Glu355 360 365Phe Arg Lys Ala Val Glu Gln His Ile Ser370 375<210>21<211>249<212>PRT<213>刺糖多胞菌NRRL30141<400>21Met Ser Arg Val Ser Gly Thr Phe Glu Glu Leu Ser Ser Val Tyr Ser1 5 10 15Pro Asp His Ala Asp Ile Tyr Asp Ala Ile His Ser Ala Arg Gly Arg20 25 30Asp Trp Ala Thr Glu Ala Glu Glu Ile Ile Gln Leu Ile Arg Thr Arg35 40 45
Leu Pro Glu Ala Gln Ser Leu Leu Asp Ile Ala Cys Gly Thr Gly Ala50 55 60His Leu Glu Arg Phe Arg Thr Glu Tyr Ala Lys Val Ala Gly Leu Glu65 70 75 80Leu Ser Asp Ala Met Arg Glu Ile Ala Ile Arg Arg Val Pro Glu Val85 90 95Pro Ile His Thr Gly Asp Ile Arg Asp Phe Asp Leu Gly Glu Pro Phe100 105 110Asp Val Val Thr Cys Leu Cys Phe Thr Ala Ala Tyr Met Arg Thr Val115 120 125Asp Glu Leu Arg Arg Val Thr Arg Asn Met Ala Arg His Leu Ala Pro130 135 140Gly Gly Val Ala Val Ile Glu Pro Trp Trp Phe Pro Asp Lys Phe Ile145 150 155 160Asp Gly Phe Val Thr Gly Ala Val Ala His His Gly Glu Arg Val Ile165 170 175Ser Arg Leu Ser His Ser Val Leu Glu Gly Arg Thr Ser Arg Met Thr180 185 190Val Arg Tyr Thr Val Ala Glu Pro Ala Gly Ile Arg Asp Phe Thr Glu195 200 205Phe Glu Ile Leu Ser Leu Phe Thr Glu Asp Glu Tyr Thr Ala Ala Leu210 215 220Glu Asp Ala Gly Ile Arg Ala Glu Tyr Leu Pro Gly Gly Pro Asn Gly225 230 235 240Arg Gly Leu Phe Val Gly Thr Arg Asn245<210>22<211>470<212>PRT<213>刺糖多胞菌NRRL30141<400>22Met Pro Ser Arg Arg Pro Leu Thr Ala Ile Gln Leu Asn Leu Tyr Pro1 5 10 15Arg Val Ala Arg His Pro Ala Val Val Gln Phe Cys Tyr Gly Gly Val20 25 30Tyr Cys Gly Pro Arg Trp Leu Gly Ser Trp Asp Trp Ile Met Ala His35 40 45Phe Val Phe Ala Thr Tyr Ala Asp His Ala His Ile Gly Pro Leu Val50 55 60Pro Val Ser Arg Ala Leu Val Glu Arg Asp His Gln Val Thr Trp Tyr
65 70 75 80Thr Gly Glu Asn Tyr Arg Ala Ala Val Glu Arg Ser Gly Ala Asp Phe85 90 95Ala Ala Pro Val Glu Gly Arg Phe Ile Asp Gly Arg Glu Leu Glu Gln100 105 110Lys Phe Pro Glu Ser Ile Gln Met Ser Ala Arg Arg Arg Ala Arg Trp115 120 125Leu Met Asp Asn His Trp Val Pro Ala Tyr Glu Gly Gln Tyr Arg Asp130 135 140Leu Val Ala Val Val Asp Arg Thr Arg Ala Asp Val Leu Leu Ala Asp145 150 155 160Ala Ser Trp Gly Pro Ala Lys Leu Val His Ala Val Thr Gly Val Leu165 170 175Trp Ala Thr Ile Ser Gln Met Pro Ile Leu Leu Pro Asp Pro Ala Val180 185 190Pro Pro Ile Gly Thr Gly Trp Lys Phe Gly Thr Ser Pro Phe His Arg195 200 205Leu Arg Asn Arg Ile Gly Asn Arg Leu Ile Asn Ala Leu Val His Asp210 215 220Pro Gly Met Lys Lys Ile Asn Ala Phe Trp Asn Ser Ile Gly Val Pro225 230 235 240Val Ser Arg Glu Val Ser Glu Ser Pro Tyr Leu Phe Met Gln Ala Gly245 250 255Thr Arg Ser Leu Glu Iyr Pro Arg Ala Leu Pro Gln Gln Met His Phe260 265 270Ile Gly Arg Leu Glu Pro Asp Ser Pro Met Gly Val Gly Leu Pro Ser275 280 285Trp Trp Gly Glu Leu Asp Gly Asp Arg Pro Val Val Leu Val Thr Gln290 295 300Gly Thr Met Ala Val Asp Ala Asp Asp Leu Ile Arg Pro Ala Leu Arg305 310 315 320Gly Leu Ala Gly Asp Gln Val Leu Val Val Ala Thr Thr Gly Arg Glu325 330 335Gly Val Asp Leu Gly Tyr Val Pro Asp Asn Ala Arg Val Ala Ser Phe340 345 350Leu Pro Tyr Arg Glu Leu Met Pro Lys Leu Ala Ala Val Val Thr Asn355 360 365Gly Gly Phe Gly Thr Val Gln Gln Ala Leu Ser His Gly Leu Pro Leu370 375 380Val Val Ala Gly Arg Ser Glu Asp Lys Thr Asp Val Cys Ala Arg Val
385 390 395 400Ala Trp Ser Gly Ala Gly Val Asp Leu Arg Thr Arg Arg Pro Ser Pro405 410 415Gln Gln Val Ala Gly Ala Val Lys Val Met Ser Thr Asp Pro Arg Tyr420 425 430Arg Gln Ala Ala Gln Arg Leu Ala Val Glu Tyr Ala Glu Tyr Asp Ala435 440 445Cys Gly Thr Ala Val Lys Leu Leu Glu Arg Leu Ala Thr Thr Arg Arg450 455 460Pro Val Ile Ala Ser Arg465470<210>23<211>169<212>PRT<213>刺糖多胞菌NRRL30141<400>23Val Arg Cys Gly Cys Gly Arg Val His Thr Ala Ala Arg Pro Glu Gly1 5 10 15Ala Arg Pro Gly Ala Val Gly Tyr Gly Pro Asn Leu Gln Ala Phe Ala20 25 30Val Tyr Leu Met Val Val His Phe Ile Pro Val His Arg Cys Val Glu35 40 45Leu Leu Ala Ser Leu Thr Gly Ala Val Pro Ser Val Gly Phe Val His50 55 60Gly Val Leu Thr Arg Ala Ala Gly Val Leu Thr Glu Val Asp Lys Arg65 70 75 80Ile His Thr Leu Ala Tyr Ala Val Cys Cys Asp Glu Thr Pro Leu Arg85 90 95Val Gly Pro Arg Thr Pro Asn Gln Ala Glu Arg Asp Leu Arg Pro Ala100 105 110Lys Val Gln Gln Asn Ile Ser Gly Arg Leu Thr Ile Glu Lys Arg Thr115 120 125Lys Asp Arg Tyr Arg Ile Arg Gly Ser Leu Ser Thr Ala Gly Lys His130 135 140Gly Arg Asn Met Ile Glu Ala Leu Arg Glu Ala Ile Arg Gly His Pro145 150 155 160Trp Met Pro Pro Asp Pro Thr Pro Ala165<210>24<211>165
<212>PRT<213>Saccharopolyspora sp.NRRL30141<400>24Val Cys Ser Asp Arg Gly Ala Gly Val Ala Leu Cyg Val Cys Trp Ser1 5 10 15Trp Cys Gly Phe Cys Val Gly Val Ala Glu Leu Ile Glu Leu Val Gly20 25 30Glu Gln Gly Ala Arg Ile Ala Val Leu Gly Glu Gln Ile Ala Val Arg35 40 45Asp Arg Gln Ile Thr Ala Met Ala Ala Gln Met Ala Glu Leu Ala Glu50 55 60Val Asn Glu Ala Leu Gly Glu Arg Leu Ala Lys Leu Glu His Ala Leu65 70 75 80Ser Arg Asn Ser Lys Asn Ser Ser Ser Ala Pro Ser Lys Asp Asp Gly85 90 95Pro Gly Arg Thr Pro Pro Pro Ala Lys Ala Lys Arg Gly Gly Ala Val100 105 110Lys Arg Lys Gly Lys Gln Pro Gly Ala Pro Gly Ala Asn Leu Ala Trp115 120 125Thr Asp Leu Pro Gly Asp His Lys Asp Arg Phe Pro Gly Gly Val Cys130 135 140Glu Cys Gly Ser Asp Leu Ala Arg Gly Thr Gly Ser Gly Gly Gly Gly145 150 155 160Ser Leu Pro Ala Ala165<210>25<211>248<212>PRT<213>刺糖多胞菌NRRL3014l<400>25Met Glu Ile Ile Gly Arg Gly Phe Ile Ala Arg Asn Leu Leu Arg Ile1 5 10 15Ser Gly Arg His Ala Asp Ala Val Ala Leu Ala Ala Gly Val Ser Asn20 25 30Thr Ser Cys Arg Ser Glu Asp Glu Tyr Gln Arg Glu Ala Ala Leu Val35 40 45Tyr Arg Thr Ile Glu Arg Cys His Ala Ile Gly Arg Lys Leu Leu Phe50 55 60Phe Ser Thr Ala Ser Ala Ser Met Tyr Gly Ala Leu Thr Ser Pro Gly65 70 75 80Phe Glu Asp Gly Pro Val Tyr Pro Pro Thr Thr Tyr Gly Arg His Lys
85 90 95Leu Ala Met Glu Ala Val Ile Lys Ala Ser Gly Val Asp Phe Leu Ile100 105 110Leu Arg Leu Ala Tyr Val Ile Gly Ala His Gln Arg Gly His Gln Leu115 120 125Leu Pro Ser Leu Val Thr Gln Leu Arg Ser Gly Ser Val Thr Val His130 135 140Arg Gly Ala His Arg Asp Val Ile Ala Ala Asp Asp Val Val Thr Ile145 150 155 160Val Asp Asp Leu Leu Thr Lys Ala Val Ala Gly Thr Val Val Asn Ile165 170 175Gly Ser Gly Phe Pro Val Pro Ala Glu Lys Ile Val Ala His Leu Glu180 185 190Tyr Arg Leu Gly Thr Ala Ala Ala Arg Gln Trp Ile Asp His Pro Thr195 200 205Glu Tyr Gln Ile Ser Leu Thr Arg Leu Asn Thr Leu Val Pro Arg Ile210 215 220Ala Glu Leu Gly Phe Gly Pro Asp Tyr Tyr Arg Gln Val Leu Asp His225 230 235 240Tyr Leu Asp Leu Tyr Pro Gln Ala245<210>26<211>260<212>PRT<213>刺糖多胞菌NRRL30141<400>26Met Phe Asp Thr Val Asp Asp Arg Ala Thr Gln Ala Leu Pro Asp Gly1 5 10 15Arg Leu Val Ala Cys Ala Asn Thr Leu Glu Val Leu Ala Ile Trp Gln20 25 30Asp Ile Ala Asn Asp Ser Ala Tyr Ala Arg Gly Leu Arg Gly Leu Gly35 40 45Ala Asp Ser Val Ile Val Asp Val Gly Ala His Val Gly Leu Ala Ser50 55 60Met Tyr Phe Ala Asp Arg Ile Pro Ala Ala Arg Ile Leu Ala Tyr Glu65 70 75 80Pro Ala Pro Thr Thr Phe Ala Cys Leu Arg Glu Asn Phe Ala Arg His85 90 95Val Pro Arg Gly Val Thr Phe AsP Leu Ala Val Gly Ala Glu Pro Gly100 105 110
Thr Ser Arg Phe Val Tyr Tyr Pro Ala Gly Pro Ser Leu Ser Thr Leu115 120 125His Leu Asp Ala Ala Asp Glu Arg Arg Asn Ile Asp Thr Val Met Ser130 135 140Asn Val Gly Ser Pro Glu Leu Ala Gly Glu Ssr Met Gln Gly Leu Val145 150 155 160Arg Thr Lys Glu Glu Leu Asp Val Arg Val Thr Thr Leu Thr Glu Ile165 170 175Ala Arg Gln His Arg Leu Asp Val Leu Asp Leu Leu Lys Ile Asp Val180 185 190Glu Arg Gly Glu Leu Asp Val Leu Asn Gly Ile Asp Asp Glu Met Trp195 200 205Pro Arg Ile Arg Arg Ile Val Val Glu Val His Asp Ile Cys Gly Arg2l0 215 220Leu Arg Gln Val Leu Asp Arg Leu Arg Lys Leu Asp Tyr Gln Val Glu225 230 235 240Val Ser Gln Ser Pro Ile Phe Leu Gly Ala Ser Val His Ile Val Val245 250 255Ala Val Arg Asp260<2l0>27<211>399<212>PRT<213>刺糖多胞菌NRRL30141<400>27Met Thr Asn Gly Asp Glu Pro Met Ala Tyr Pro Phe Gly Glu Ile Asp1 5 10 15Arg Leu Leu Leu Asp Asp Arg Tyr Ala Val Leu Arg Glu Gly Glu Pro20 25 30Val Ser Lys Ile Arg Leu Pro Tyr Gly Gly Asp Gly Trp Leu Val Thr35 40 45Arg Tyr Ala Asp Ile Lys Thr Val Leu Gly Asp Pro Arg Phe Ser Ala50 55 60Ala Ala Ile Leu Asn Arg Asp Val Pro Arg Gly Phe Pro Leu Ile Leu65 70 75 80Arg Glu His Ser Leu Gly Thr Met Asp Pro Pro Glu His Thr Arg Leu85 90 95Arg Lys Leu Val Gly Lys Ala Phe Thr Ala Arg Arg Val Glu Gln Leu100 105 110Arg Pro Arg Thr Gln Gln Leu Val Asp His Leu Leu Asp Arg Met Ala115 120 125
Ala Asp Gly Pro Pro Gly Asp Leu Val ser Ala Leu Ala Leu Pro Leu130 135 140Pro Ile Lys Val Ile Cys Asp Leu Leu Gly Ile Pro Val Ala Asp Arg145 150 155 160Glu Arg Phe Arg Val Trp ser Asp Ile Ala Leu Ala Ile Thr Ser Asn165 170 175Ser Pro Glu Glu Ile Arg Glu Ser Arg Asp Gln Ile Arg Ala Tyr Ile180 185 190Gly Glu Leu Val Gln Gln Arg Lys Lys Met Pro Thr Glu Asp Leu Leu195 200 205Ser Val Leu Val Gln Ala Arg Ala Glu Gly Ala Gln Leu Ser Glu Glu210 215 220Glu Ile Val Val Thr Gly Ala Gly Leu Leu Ile Ala Gly Phe Glu Thr225 230 235 240Thr Ala Asn His Ile Ala Asn Phe Thr Phe Asn Leu Leu Thr His Pro245 250 255Asp Gln Leu Asp Lys Leu Ile Ala Asp Pro Glu Leu Val Pro Arg Ala260 265 270Val Glu Glu Leu Leu Arg Tyr Thr Pro Leu Gly Ala Thr Pro Gly Phe275 280 285Pro Arg Ile Ala Thr Glu Asp Leu Glu Leu Gly Gly Val Ser Ile Arg290 295 300Arg Gly Asp Ala Val Phe Phe Glu Ile Ala Ser Ala Asn Arg Asp Ser305 310 315 320Ala Val Phe Asp Gly Pro Asp Glu Leu Asp Leu Ala Arg Glu His Asn325 330 335Ser His Met Ala Leu Gly His Gly Pro His Tyr Cys Ile Gly Ala Gln340 345 350Leu Ala Arg Met Glu Leu Gln Val Ala Ile Gly Thr Leu Ile Lys Arg355 360 365Phe Pro Gln Leu Ser Phe Ala Val Pro Val Asp Glu Val Val Trp Lys370 375 380Arg Gly Arg Met Thr Arg Gly Pro Glu Ala Leu Pro Ile Thr Trp385 390 395<210>28<211>248<212>PRT<213>刺糖多胞菌NRRL30141<400>28Val Val Arg Asn Gly His Asp Gln Pro Arg Glu Val Leu Thr Ser Ala
1 5 10 15Gly Ala Val Glu Val Thr Ala Pro Arg Val Asn Asp Lys Arg Thr Asp20 25 30Pro Asp Thr Gly Ala Arg Arg Arg Phe Ser Ser Ala Ile Leu Pro Pro35 40 45Trp Ala Arg Lys Thr Pro Lys Ile Thr Glu Met Leu Pro Leu Leu Tyr50 55 60Leu His Gly Leu Ser Ser Gly Asp Phe Val Pro Ala Leu Gly Gln Phe65 70 75 80Leu Gly Ser Ser Lys Gly Leu Ser Ala Thr LeuIle Thr Lys Leu Thr85 90 95Glu Gln Trp Arg Thr Glu His Arg Ala Phe Asn Glu Arg Gly Leu Ser100 105 110Glu Val Asp Phe Val Tyr Leu Arg Ala Asp Gly Ile His Val Asn Ile115 120 125Arg Leu Glu Glu His Lys Leu Ser Leu Leu Val Val Ile Gly Val Arg130 135 140Ala Asp Gly Arg Lys Glu Leu Val Ala Leu Ala Asp Gly Tyr Arg Glu145 150 155 160Ser Thr Glu Ser Trp Ala Gly Leu Thr Tyr Cys Val Thr Ala Ser Ala165 170 175Ala Val Cys Val Pro Arg Tyr Trp Pro Ser Ala Thr Val His Trp Gly180 185 190Ser Gly Ala Arg Ser Ala Arg Leu Ser Leu Ile Arg Ala Ser Ser Ala195 200 205Thr Gly Ser Thr Arg Ser Ala Met Cys Ser Pro Arg Cys Arg Asn Arg210 215 220Arg Ile Pro Ala Arg Arg Arg Pro Trp Pro Arg Ser Gly Met Pro Arg225 230 235 240Thr Ala Gly Thr Cys Trp Thr Arg245<210>29<211>276<212>PRT<213>刺糖多胞菌NRRL30141<400>29Val Ala Glu Thr Ile Gly Leu Val Arg Arg Thr Ser Ser Gly Gln Leul 5 10 15Ala Glu Thr Glu Leu Leu Ala Leu Leu Arg Arg Asp Gly Gly Arg Tyr20 25 30
Arg Ser Thr Val Leu Ala Leu Thr Ala Pro Gly Phe Asn Arg Pro Ser35 40 45Glu Met Met His Arg Ala Val Leu Ser Gly Arg Ala His Thr Ala Gln50 55 60Val Leu Gly Thr Asp Leu Trp Gly Tyr Tyr Gly Thr Asn Pro Glu Glu65 70 75 80Ala Lys Trp Phe Gly Gly Ala Met Thr Asp Leu Thr Asn Leu Val Ala85 90 95Asp Leu Val Leu Ala Arg Tyr Glu Phe Ser Gly Arg Gly Thr Ile Met100 105 110Asp Val Gly Gly Ser His Gly Ile Phe Leu Ser Arg Ile Leu His Ala115 120 125Gln Pro Asp Ala Lys Gly Val Leu Phe Asp Arg Met Glu Val Val Glu130 135 140Glu Ala Arg Asn His Leu Asp Gln Asp Ile Arg Thr Arg Ile Gln Ile145 150 155 160Val Gly Gly Asr Phe Phe Glu Gly Val Pro Glu Gly Gly Asp Leu Tyr165 170 175Ile Leu Lys Ser Val Leu Cys Asp Trp Asp Asp Gln Ser Cys Leu Gln180 185 190Ile Leu Ser Arg Ile Arg Asn Ala Ala Met Pro Gly Ala Ser Lau Leu195 200 205Ile Val Asp Trp Leu Tyr Pro Asp Glu Ser Asp Pro Gly Leu Asp Ala210 215 220Ile Tyr Leu Gln Gln Ala Ile Ser Val Asn Gly Arg Val Arg Asn Gln225 230 235 240Glu Gln Phe Glu Ser Leu Leu Lys Ala Thr Gly Phe Ala Val Thr Arg245 250 255Val Glu Arg Thr Thr Pro Glu Asn Trp Ile Pro Ala Thr Ile Ile Glu260 265 270Ala Ile Arg Arg275<210>30<211>616<212>PRT<213>刺糖多胞菌NRRL30141<400>30Val Gly Cys Leu Arg Ser His Ala Ala Tyr Pro Ala Ser Ala Asp Gln1 5 10 15Gly Ala Leu Leu Arg Asp Pro Val Arg Arg Gly Val Gln Pro Gly Arg
20 25 30Ala His Asp Arg His Arg Arg Arg Thr Arg Arg His Arg Ala Gly Arg35 40 45His Tyr Arg Pro Gly Gln Ser Gln Gly Ala Asn Arg Pro Leu Gly Thr50 55 60Leu Arg Gln Val Asp Asp Leu Gly Gly Val Gln Pro Gly Arg Gly Lys65 70 75 80Val Gly His Gln Arg Arg Arg Arg His Arg Cys Pro Val Val Pro Arg85 90 95Arg Pro Ala Ala Pro Thr Ala Ala Gly Asp Ala Gly Arg Pro Arg Arg100 105 110Gln GLy Val Arg Ser Gly Val Gln Leu Glu Arg Gly Gly Gly Leu His115 120 125Arg Gly Phe Leu Arg Asn Arg Arg Ser Arg Gly Ala Val Arg Gln Trpl30 135 140Arg Ala Ala Asp Arg Ala Arg Pro Val Ala Thr Gly Leu Leu Asn Gly145150 155 160His Glu Leu Arg Leu Thr Ala Val Ser Thr Val Asp Asp Ser Ala Leu165 170 175Ala Ile Ala Ser Lys Pro Arg Ser Pro Ile Pro Asp Pro Arg Cys Lys180 185 190Val Ala Thr Thr Ser Ser Ala Ser Ser Pro Leu Pro Gly Leu Gly Pro195 200 205Val Val Arg Ser Asn Phe Gly Pro Thr Arg Leu Gly Phe Val Leu Met210 215 220Leu Lys Phe Phe Glu Leu Glu Gly Arg Phe Pro Gln Phe Val Glu Glu225 230 235 240Phe Pro Gln Ala Ala Val Asp Tyr Val Ala Gly Val Val Lys Val Pro245 250 255Ala Glu Asp Leu Ala Lys Tyr Xaa Leu Ser Ser Arg Ser Ala Lys Gly260 265 270His Arg Thr Gln Ile Arg Glu Thr Leu Gly Tyr Xaa Pro Ala Thr Arg275 280 285Ala Asp Glu Glu Arg Leu Thr Ala Trp Leu Ala Asp Glu Val Cys Pro290 295 300Val Glu Met Val Glu Asp Arg Leu Arg Glu Ala Leu Leu Val Gln Cys305 310 315 320Arg Ser Asp His Val Glu Pro Pro Gly Arg Val Glu Arg Ile Val Ala325 330 335Ala Ala Arg Ala Arg Ala Asp Arg Val Phe Cys Ala Gln Thr Val Ala
340 345 350Arg Leu Gly Glu Ala Cys Ala Gly Arg Leu Leu Thr Leu Val Ala Glu355 360 365Gly Asn Glu Glu Gly Thr Ala Leu Leu Ala Ser Leu Lys Arg Asp Pro370 375 380Gly Ala Val Gly Leu Asp Ser Leu Leu Ala Glu Ile Thr Lys Leu Thr385 390 395 400Ala Val Arg Arg Leu Gly Leu Pro Glu Gly Leu Phe Ala Asp Cys Ser405 410 415Glu Lys Leu Val Ala Ala Trp Ala Gly Ala Gly Asp Gln Asp Val Ser420 425 430Leu Gly Leu Pro Gly Arg Trp Gln Gly Cys Ala Asp His Ala Ala Gly435 440 445Gly Ala Val Arg Val Pro Ala Gly Gly Asp His Arg Cys Pro Gly Gly450 455 460Ala Ala Gly Arg Ser Gly Ser His Lys Ile Asn Ala Arg Ala Glu Arg465 470 475 480Arg Val Glu Arg Gln Leu Thr Ala Glu Leu Lys Lys Val Arg Gly Lys485 490 495Glu Gly Ile Leu Phe Gln Leu Ala Asp Ala Ser Val Gly Gln Pro Glu500 505 510Gly Thr Val Arg Arg Val Leu Phe Pro Val Val Gly Glu Lys Thr Leu515 520 525Arg Asp Leu Val Ala Glu Ala Asn Glu Lys Ala Phe Lys Ala Arg Val530 535 540Arg Thr Thr Leu Arg Ser Ser Tyr Ser Ser Tyr Tyr Pro Ala Asp Ala545 550 555 560Ala Val Thr Ala Ala Asp Ala Arg Leu Gln Val Gln Gln His Arg Leu565 570 575Pro Ala Gly Asp Gly Arg Ala Arg Ala Ala Gly Glu Val Arg Arg Arg580 585 590Arg Arg Gln Asp Pro Leu Leu Arg Arg Arg Arg Arg Gly Ala Asp Gly595 600 605Arg Pro Ser Pro Gln Gly Leu Ala610 615<210>31<211>458<212>PRT<213>刺糖多胞菌NRRL30141<400>31
Val Leu Ile Phe Asp Arg Gly His Ala Glu Lys Ile Arg Gln Glu Tyr1 5 10 15Ala Cys His Phe Asn Thr His Arg Pro His Gln Ala His Asp Gln Gln20 25 30Ala Pro Tyr Val Ala Arg Ala Ser Tyr Arg Cys Arg Gln Leu Gly Ser35 40 45Asn Ala Asp Lys Pro Trp Gln Asp Ser Ser Thr Ser Thr Ala Lys Gln50 55 60Pro Asp Gly Pro Thr Lys Pro Gln Leu Thr Ala Ser Glu Pro Phe Leu65 70 75 80Lys His Tyr Gly Ser Cys Cys Ser Pro Arg Ser Ser Arg Cys Arg Ser85 90 95Ala Gly Arg Ser Arg Phe Gln Glu Asp Gln Pro Val Trp Ser Pro Cys100 105 110Arg Pro Ala Glu Ala Ala Pro Thr Thr Gly Trp Thr Ser Gly Val Leu115 120 125Ala Arg Arg Thr Ala Gly Val Arg Asn Arg Pro Tyr Arg Arg Gly Ser130 135 140Gln His Thr Cys Gly Thr Trp Ser Arg Gln Gly Pro Gly Arg Gly Thr145 150 155 160Gly Val His His Phe Arg Arg Ser Gly Leu Asp His Asp Pro Ala Leu165170 175Pro Arg Tyr Cys Phe His Arg Glu Arg Ala Ala Val Gln Val Thr Phe180 185 190Glu Arg Phe Asp Ala Val Val Ala Glu His Ser Leu Gly His Ala Lys195 200 205Tyr Gly Gly Ser Val Tyr Glu Lys Arg Asp Leu G1y Gln Gln Val Pro210 215 220Cys Arg His Val Gln Leu Phe Leu Arg Glu Thr Ala Val Gly Ser Pro225 230 235 240Pro Ala Pro Arg Asp Arg Phe Arg Leu Gly Gln Thr Gly Leu Pro Glu245 250 255Val Phe Ile Arg Pro Glu Asp Leu Arg Asn Leu Val Pro Arg Ala Gln260 265 270Val Leu Leu Val Leu Val Glu Pro Gly Glu Val Asp Asp His Leu Leu275 280 285Gly Gly Arg Asp Ala Glu His Gly Lys Arg Pro Glu Tyr Leu Pro Ala290 295 300Gln Pro Ser Cys Leu Ala Ser Arg Leu Pro Leu Cys Phe His Arg Arg305 310 315 320
Ile Ala Ala Gly Leu His Arg Glu Ser Gly Gly Arg Val Arg Glu Glu325 330 335His Met Gln Arg Leu Glu Leu Gly His Arg Pro Pro Gln Glu Leu Val340 345 350Gln Ser Cys Leu Phe Glu Val Ala Val Glu Lys Ser Cys Ala Asn Lys355 360 365Gly Val Ser Thr Pro Leu Glu Asp Pro Gly Ala Leu Leu Gly Arg Arg370 375 380Phe Met Pro His His Lys Leu Gly Ile His Val His Ala Ser Ser Arg385 390 395 400His Gly Cys Ile His Val Val Cys Thr Phe Cys Leu Glu Thr Val Ala405 410 415Ser Ser Thr Leu Arg Gln Leu Arg Arg Ile Leu Tyr Ala Asn Leu Asp420 425 430Ala Leu Asp Ser Pro Leu Gln Arg Phe Arg Ile Cys Ala Arg Glu Pro435 440 445Arg Ala Glu Arg Gly Ile Pro Phe Pro Gln450 455<210>32<211>305<212>PRT<213>刺糖多胞菌NRRL30141<400>32Val Asp Val Ala Phe Cys Ala Ile Cys Gly Ser Asp Leu His Leu Arg1 5 10 15Ala Met Pro His Leu Val Pro Ala Asp Ala Val Leu Gly His Glu Ile20 25 30Ser Gly His Val Ala Ala Pro Gly Gly Glu Arg Leu Thr Ala Gly Gln35 40 45Ala Val Val Val Trp Pro Lys Ala Gly Cys Gly Asp Cys Asp Asp Cys50 55 60Arg Val Gly Asp Asn His Leu Cys Ala Val Gln Pro Trp Arg Leu Ser65 70 75 80Ser Leu Gly Leu Gly Thr Arg Pro Gly Gly Tyr Ala Glu Ala Val Val85 90 95Val Pro Glu His Thr Val Tyr Ala Val Pro Asp Gly Val Ser Leu Glu100 105 110His Ala Ala Leu Thr Glu Pro Leu Ser Cys Ala Val His Ala Val Asp115 120 125Arg Ser Gly Ile Ser Ala Ala Asp Thr Val Thr Val Leu Gly Gly Gly130 135 140
Thr Val Gly Phe Leu Leu Ala His Val Leu Arg Leu Arg Gly Val Glu145 150 155 160Asp Val Arg Val Val Glu Pro His Pro Val Arg Arg Ala Arg Leu Thr165 170 175Ala Thr Gly Ile Thr Thr Val Asp Val Asp Glu Arg Gly Pro Asp Ala180 185 190Asp Val Val Phe Glu Cys Val Gly Ser Val Thr Ala Leu Thr Asp Ala195 200 205Ala Arg Arg Val Arg Thr Arg Gly Thr Ile Val Ala Leu Gly Val Asn210 215 220Glu Arg Pro Ser Glu Leu Asp Ser Val Ala Leu Ile Thr Lys Glu Ile225 230 235 240Arg Ile Val Gly Ser Phe Ala Gln Asn Arg Gly Ala Phe Glu Ala Ala245 250 255Leu Glu Leu Leu Gly Gly Gly Arg Ile Pro Val Glu Arg Ile Ile Thr260 265 270Asp Val Val Pro Leu Asp Ala Gly Pro Val Ser Ala Met Met Asp Ala275 280 285Leu Thr Gly Arg Pro Gly Asp His Gln Val Val Met Ile Ala Pro Gly290 295 300Gly305<210>33<211>20<212>DNA<213>刺糖多胞菌<400>33gtgccgaata cgcgaaggtc 20<210>34<211>20<212>DNA<213>刺糖多胞菌<400>34tccaggaagg tattccgcgc 20<210>35<211>20<212>DNA<213>刺糖多胞菌<400>35gcgacaacgc gatccagatc 20
<210>36<211>22<212>DNA<213>刺糖多胞菌<400>36ccatgtcgtg ggcatatttc tc 22<210>37<211>21<212>DNA<213>刺糖多胞菌<400>37tcccgatgcc tggattcatt g21<210>38<211>22<212>DNA<213>刺糖多胞菌<400>38cgtccatcat cgagaagtgg tc 22<210>39<211>16<212>DNA<213>刺糖多胞菌NRRL 30141<400>39cgtacgtggc gatcag 16<210>40<211>21<212>DNA<213>刺糖多胞菌NRRL 30141<400>40gtccaagttt cggttgcgtt c2权利要求
1.分离的DNA分子,其含有编码丁烯基-多杀菌素生物合成酶的DNA序列,其中构成该酶的氨基酸序列同选自SEQ ID NO 3-7和8-29的序列之一至少有98%同一性,前提是假如该序列同所选择的序列并非100%同一,那么它们之间的区别实质上并不影响所编码酶的功能特性。
2.权利要求1的分离的DNA分子,其中DNA序列是选自于busA、busB、busC、busD、busE、ORF RI、ORF RII、ORF RIII、busF、busG、busH、busI、busJ、busK、busL、busM、busN、busQ、busP、busQ、busR、busS、ORF LI、ORF LII、ORF LIII、ORF LIV、ORF LVI、ORF LVII、ORF LVIII和ORF LIX,所述基因分别由SEQ ID NO1的碱基1-13032、13059-19505、19553-29053、29092-43890、43945-60636、62090-63937、65229-66602和SEQ ID NO2的碱基114-938、1389-2558、2601-3350、3362-4546、4684-6300、6317-7507、7555-8403、8640-9569、9671-10666、10678-12135、12867-14177、14627-15967、16008-17141、17168-17914、18523-19932、19982-20488、20539-21033、21179-21922、22674-23453、23690-24886、26180-26923以及27646-28473。
3.分离的DNA分子,其含有编码丁烯基-多杀菌素PKS结构域的DNA序列,该结构域选自于KSi、ATi、ACPi、KSb、ATb、KRb、DHb、ACPb、KS1、AT1、KR1和ACP1,所述结构域分别由SEQ ID NO3的氨基酸7-423、528-853、895-977、998-1413、1495-1836、1846-2028、2306-2518、2621-2710、2735-3160、3241-3604、3907-4086以及4181-4262所描述。
4.权利要求3的分离的DNA分子,其中DNA序列选自SEQ ID NO1的碱基16-1269、1582-2559、2683-2931、2992-4239、4483-5508、5538-6084、6916-7554、7861-8130、8203-9480、9721-10812、11719-12258以及12541-12786。
5.分离的DNA分子,其含有编码多杀菌素PKS结构域DNA序列,该结构域选自于KS2、AT2、DH2、ER2、KR2和ACP2,所述结构域分别由SEQ ID NO4的氨基酸1-421、534-964、990-1075、1336-1681、1685-1864以及1953-2031所描述。
6.权利要求5的分离的DNA分子,其中DNA序列选自SEQ ID NO1的碱基13059-14321、14658-15900、16026-16283、17064-18100、18111-18650以及18915-19151。
7.分离的DNA分子,其含有编码多杀菌素PKS结构域的DNA序列,该结构域选自于KS3、AT3、KR3、ACP3、KS4、AT4、KR4和ACP4,所述结构域分别由SEQ ID NO5的氨基酸1-421、528-814、1157-1335、1422-1503、1526-1949、2063-2393、2697-2875、以及2969-3049所描述。
8.权利要求7的分离的DNA分子,其中DNA序列选自SEQ ID NO1的碱基19553-20815、21143-22000、23021-23557、23816-24061、24128-25399、25739-26731、27641-28183以及28457-28699。
9.分离的DNA分子,其含有编码多杀菌素PKS结构域的DNA序列,该结构域选自KS5、AT5、DH5、KR5、ACP5、KS6、AT6、KR6、ACP6、KS7、AT7、KR7以及ACP7,所述结构域分别由SEQ ID NO6的氨基酸1-422、537-864、891-1076、1382-1563、1643-1724、1746-2170、2281-2611、2914-3093、3186-3267、3289-3711、3823-4151、4342-4636以及4723-4804所描述。
10.权利要求9的分离的DNA分子,其中DNA序列选自SEQ ID NO1上碱基29092-30357、30700-31683、31762-32319、33235-33780、34018-34263、34327-35601、35932-36924、37831-38370、38647-38892、38956-40224、40560-41544、42115-42999以及43258-43503。
11.分离的DNA分子,其含有编码多杀菌素PKS结构域的DNA序列,该结构域选自KS8、AT8、DH8、KR8、ACP8、KS9、AT9、DH9、KR9、ACP9、KS10、AT10、DH10、KR10、ACP10以及TE10,所述结构域分别由SEQ IDNO7的氨基酸1-424、530-848、885-1072、1371-1554、1650-1728、1751-2175、2289-2616、2642-2775、3131-3315、3396-3474、3508-3921、4036-4366、4389-4569、4876-5054、5148-5229以及5278-5531所描述。
12.权利要求11的分离的DNA分子,其中DNA序列选自SEQ ID NO1的碱基43945-45216、45532-46488、46597-47160、48055-48606、48892-49083、49195-50469、50809-51792、51868-52269、53335-53889、54130-54366、54466-55707、56050-57042、57109-57651、58570-59106、59386-59631以及59776-60537。
13.分离的DNA分子,其含有编码多杀菌素PKS模块的DNA序列,所述模块分别由SEQ ID NO3的氨基酸6-977、998-2710以及2735-4262;SEQ ID NO4的氨基酸1-2031;SEQ ID NO5的氨基酸1-1503和1526-3049;SEQ ID NO6的氨基酸1-1724、1746-3267以及3289-4804;SEQ ID NO7的氨基酸1-1728、1751-3474以及3508-5531所描述。
14.权利要求13的分离的DNA分子,其中DNA序列选自SEQ ID NO1的碱基16-2931、2992-8130、8203-12786、13059-19151、19553-24061、24128-28699、29092-34262、34327-38893、38956-43503、43945-49083、49195-54366以及54466-60537。
15.重组DNA载体,其含有权利要求1-14的任意一项的DNA序列。
16.用权利要求15的重组载体转化的宿主细胞。
17.提高产多杀菌素微生物生产多杀菌素能力的方法,包括下列步骤1)用重组DNA载体或其部分转化微生物,后者借助生物合成途径生产丁烯基-多杀菌素或其前体,该载体或其部分含有本发明的上述DNA序列,该序列编码所述途径中限速活性的表达。2)在适于细胞生长和分裂、适合上述DNA序列表达以及多杀菌素生产的条件下,培养用上述载体转化的上述微生物。
18.丁烯基-多杀菌素的制备方法,包括培养其基因组中含有可操作的丁烯基-多杀菌素生物合成基因的微生物,前提是该生物的基因组经修饰而存在至少下列丁烯基-多杀菌素生物合成基因之一的复制拷贝——busA、busB、busC、busD、busE、busF、busG、busH、busI、busJ、busK、busL、busM、busN、busO、busP、busQ、busR和busS。
19.丁烯基-多杀菌素的制备方法,包括培养其基因组中含有丁烯基-多杀菌素生物合成基因的微生物,前提是所述基因中至少一个被失活,而剩下的基因可操作地产生除被破坏的基因能可操作地产生的产物以外的丁烯基-多杀菌素。
20.丁烯基-多杀菌素的制备方法,包括培养转化后其基因组中含有可操作性的丁烯基-多杀菌素生物合成基因的异源微生物。
21.丁烯基-多杀菌素的制备方法,其包括培养其基因组中具有可操作性的丁烯基-多杀菌素生物合成基因的微生物,其中所述基因a)包括的可操作性的PKS模块比SEQ ID NO1中所存在的至少多一个或至少少一个;b)包含由于缺失、失活或增添KR、DH或ER结构域,或由于替换AT结构域而与SEQ ID NO1中所述的相应模块不同的PKS模块。
22.分离丁烯基-多杀菌素生物合成基因的方法,包括构建产丁烯基-多杀菌素微生物的基因组文库,以及用SEQ ID NO1或SEQ ID NO2的至少20个碱基长的标记片段作杂交探针。
全文摘要
本发明提供丁烯基-多杀菌素生物合成基因、用这些基因转化的产多杀菌素的微生物、用这些基因提高丁烯基-多杀菌素杀虫性大环内酯产量的方法及用这些基因或其片段来改变产多杀菌素的微生物生产的产品的方法。
文档编号C12N1/19GK1507493SQ02809080
公开日2004年6月23日 申请日期2002年3月28日 优先权日2001年3月30日
发明者D·R·哈恩, J·D·杰克逊, B·S·布拉德, G·D·古斯塔弗森, C·沃尔德伦, J·C·米切尔, D R 哈恩, 侣, 古斯塔弗森, 布拉德, 杰克逊, 米切尔 申请人:道农业科学公司
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