毒力基因、蛋白质及其用途的制作方法

专利名称：毒力基因、蛋白质及其用途的制作方法
技术领域：
本发明涉及毒力基因和蛋白质，及其用途。更具体地说，本发明涉及从酿脓链球菌(Streptococcus pyogenes)获得的基因和蛋白质/肽，及其在治疗和筛选药物方面的用途。
背景技术：
A群链球菌(GAS)是大多数链球菌疾病的病因。特别令人感兴趣的一种生物是酿脓链球菌，它涉及很多非侵袭性和侵袭性感染，例如脓庖疮、咽炎、坏死性筋膜炎、菌血症、链球菌中毒性休克综合征(STSS)、肺炎和风湿热。
一些GAS感染可以使用抗生素治疗，包括青霉素和红霉素。然而，由于与抗生素耐药和抗生素过敏患者相关的问题，需要另外可用于治疗或预防GAS感染的疗法。
发明概述本发明基于酿脓链球菌中毒力基因的发现。
根据本发明的第一方面，本发明的肽是由操纵子编码的，其包含任何如下所示来自酿脓链球菌的核苷酸序列SEQ ID NO1，3，5，7，9，11，13，15，17，19，21，23，25，27，29，31，33，35，37，39，41，43，45，47，49，51，53，55，57，59和61，或其在革兰氏阳性细菌中的同源物，或其功能片段，用于治疗或诊断。
所述肽对治疗A群链球菌感染可具有许多治疗用途，包括在预防应用疫苗中的用途。
根据第二方面，编码如上定义的肽的多核苷酸，也可以用于治疗或诊断。
根据第三方面，编码所述肽的基因可用于制备减毒微生物。减毒微生物通常有一个突变，该突变破坏一个或多个本文鉴定的基因的表达，提供缺乏毒力的菌株。这些微生物也可以用于治疗和诊断。
根据第四方面，根据本发明的肽、基因和减毒微生物可用于治疗或预防与链球菌或革兰氏阳性菌感染相关的病症。
发明详述本发明基于编码涉及毒力的肽的基因的发现。因此本发明的肽和基因可用于制备治疗感染的治疗剂。应该理解所指的治疗也包括预防性治疗，例如，接种疫苗。此外，尽管本发明的产物主要旨在治疗人类患者的感染，兽医应用也被认为是在本发明的范围内。
本发明参考酿脓链球菌进行描述，然而，所有的A群链球菌菌株和许多其他革兰氏阳性菌菌株也可能包含与本文鉴定的蛋白质具有氨基酸序列同一性或相似性的相关肽或蛋白质。可能包含所述肽的生物包括但不限于乳球菌属(Lactococcus)、肠球菌属(Enterococcus)、链球菌属(Streptococcus)和葡萄球菌属(Staphylococcus)。
可用于本发明的各个方面的肽优选与本文鉴定的肽有大于40％的相似性。更优选所述肽有大于60％的序列相似性。最优选所述肽有大于80％的序列相似性，例如95％的相似性。关于本文鉴定的多核苷酸序列，可用于本发明的各个方面的相关多核苷酸序列可与本文鉴定的序列有大于40％的同一性。更优选所述多核苷酸序列有大于60％的序列同一性。最优选所述多核苷酸序列有大于80％的序列同一性，例如95％的同一性。
术语“相似性″和“同一性”在本领域中是公知的。所用的术语“同一性”是指基于在所比较序列对应相同位置之间相同配对的序列比较。术语“相似性”是指氨基酸序列之间的比较，而且不仅考虑在对应位置相同的氨基酸，还考虑在对应位置上功能相似的氨基酸。因此多肽序列之间的相似性表示除序列相似性之外还具有功能相似性。
基因序列之间的同一性水平和氨基酸序列间之间的同一性或相似性水平可以使用公知的方法计算。对于本发明，可公开获得的基于计算机的确定同一性和相似性的方法包括BLASTP，BLASTN和FASTA(Atschul等，分子生物学杂志(J.Molec.Biol.)，1990；215403-410)，获自NCBI的BLASTX程序，和获自Genetics Computer Group，Madison WI的Gap程序。本文提供的相似性和同一性水平是使用Gap程序获得的，用Gap罚为12和Gap长度罚为4来确定氨基酸序列比较，用Gap罚为50和Gap长度罚为3来进行多核苷酸序列比较。
已表征根据本发明的基因，从而可能将所述基因序列用于在其他微生物中搜索相关基因或肽。这可以通过在现存的数据库中搜索来进行，例如，EMBL或GenBank。
根据本发明的肽或蛋白质可用本领域公知的方法进行纯化和分离。具体地说，已鉴定了所述基因序列，从而可能用重组技术在合适的宿主中表达所述基因。可鉴定活性片段和相关分子并将其用于治疗。例如，可将肽或其活性片段作为抗原决定簇用于疫苗中，激发免疫应答。也可以将它们用于抗体制备，进行被动免疫或用于诊断。合适的抗体包括单克隆抗体，或其片段，包括单链Fv片段。制备抗体的方法对本领域技术人员是显而易见的。
所述肽的活性片段是那些保持所述肽的生物功能的片段。例如，当用于激发免疫应答时，该片段具有足够的大小，使得由该片段生成的抗体能区分所述肽和细菌微生物上的其他肽。通常该片段的大小为至少30个核苷酸(10个氨基酸)，优选60个核苷酸(20个氨基酸)，最优选大于90个核苷酸(30个氨基酸)。
也可以理解，除了来自其他微生物的相关分子之外，本发明包括对本文鉴定的肽和多核苷酸所做的修饰，所述修饰并不显著改变其生物学功能。遗传密码简并性可以产生具有与本文指明的序列相比只有小的碱基改变但仍编码相同肽的多核苷酸，这对本领域技术人员是显而易见的。互补的多核苷酸也包括在本发明内。在氨基酸水平上的保守置换也是可以想见的，即不同的酸性或碱性氨基酸可以被置换，而功能无实质丢失。
制备基于减毒微生物的疫苗对本领域技术人员是已知的。可用合适的载体或佐剂，例如明矾，作为必要的或所希望的成分，来配制疫苗组合物，以提供有效的免疫对抗感染。疫苗制剂的制备对本领域技术人员是显而易见的。可以制备减毒微生物，其具有破坏本文鉴定的任何基因的表达的突变。本领域技术人员已知破坏特定基因表达的方法。可采用的技术包括插入失活或基因缺失技术。根据本发明的减毒微生物还可包含其他基因的另外突变，例如，在本文鉴定的第二个基因或在微生物生长所需要的单独基因上，如aro突变。减毒微生物还可以用做递送异源抗原、治疗性蛋白质或核酸(DNA或RNA)的载体系统。在该实施方案中，将所述减毒微生物用于递送异源抗原、蛋白质或核酸至体内特定位点。可以通过传统的技术将异源抗原、肽或核酸引入减毒微生物，这些技术包括利用重组构建体，如载体，其包含表达异源抗原或治疗性蛋白质的多核苷酸，还包括合适的启动子序列。或者，可将编码异源抗原或蛋白质的基因掺入生物体的基因组中，并使用内源启动子控制表达。
更通常的，也是本领域技术人员熟知的是，可以选择合适量的本发明的活性成分，以及合适的载体或赋形剂和给药途径，用于治疗。可根据已知的指标选择或确定这些因素，如所治疗病症的性质/严重程度、受治疗者类型和/或健康状况等。
在一个独立的实施方案中，本发明的产物可用于鉴定有效抗微生物药物，或检测毒力的筛选试验。常规筛选试验是本领域技术人员已知的，也可以作修改，以适当的方法使用本发明的产物。例如，可将本发明的产物用作有效药物的目标，所述药物能灭活或结合目标则表明药物有潜在的抗微生物活性。
本发明的各种产物也可以用于兽医应用。
下面是用于鉴定毒力基因的试验方法的简要概述。通过使用特征标记诱变(STM)在酿脓链球菌突变体库中筛选减毒突变体来鉴定酿脓链球菌的毒力基因(Hensel等，1995.科学(Science)269(5222)400-3)。
使用质粒载体，通过Tn917转座子插入而产生突变体。除Tn917片段以外，所用载体还包括链霉素耐药基因，带有合成启动子的氯霉素耐药基因(CAT基因)，革兰氏阴性菌复制起点(rop.ori)和STM标记的克隆位点。将标记连接入载体后，进行大肠杆菌转化，选出96个与最初标记杂交的质粒。
用所得的96个标记质粒的每一个分别转化酿脓链球菌菌株B514-SM(M50型)，通过对链霉素和氯霉素的抗性筛选出转化体。对每一个经转化的酿脓链球菌菌株，通过Tn917转座子插入产生20个突变体而创建一个突变体库。
在小鼠感染的皮肤侵袭性损伤模型中筛选突变体库(Schrager等，临床研究杂志(J.Clinical Investigation)1996；981954-1958)，或从小鼠感染的咽喉定植模型筛选突变体库(Husmann等，感染和免疫(Infection and Immunity)，1997；65(4)935-944)。
在皮肤模型中，用在50μl体积中的1×108细胞对五只CD1老鼠各自进行皮内接种，这些细胞代表96个不同的并易于区分的突变体的集合。在接种后48小时，取样并回收细菌。将皮损浸在2×BHI培养基中，通过在细菌分离器中处理10分钟将细菌从皮损中释放出来。将释放出来的细菌铺板，从最少3只小鼠回收最少10,000个菌落。从这些样本中分离DNA并用来扩增在回收细菌中的标记的DNA。将从各回收库中分离的DNA用作杂交探针，以显示在各库中不能从动物回收的、因此在该动物感染模型中减毒的那些突变体。
在咽喉定植模型中，将2×108个细菌鼻内接种至6只C57BL/6小鼠，48小时后取样。与皮肤模型一样，在毒力基因中含有转座子Tn917插入的细菌不能从用突变体混合群接种的小鼠中回收，因此可能是减毒的。
对通过STM筛选鉴定的突变体进行了附加的试验，来确定竞争指数(CI)。在用感染的皮损模型中的野生型菌株进行的混合感染中测试各突变体。(Chiang，S.L.和Mekalanos，J.J.分子微生物学(MolecularMicrobiology)1998；27(4)797-805).对于初始筛选，用相等数目的野生型和突变型细胞，至总数为1×108细胞接种含4只CD1小鼠的组。将48小时后回收的细菌铺到选择性培养基平板上，从而可区分野生型菌落和突变体菌落。在接种物中突变体细菌与野生型细菌的比值与回收细菌中该比值之比即竞争指数(接种物中突变体对野生型的比值除以从动物模型回收的突变体对野生型细菌的比值)下列实施例详细说明了本发明。
实施例1鉴定第一个突变体，并克隆紧接转座子插入的核苷酸序列。
所述核苷酸序列，在核苷酸水平表现出与酿脓链球菌基因组中如SEQID NO.1所示的编码序列100％的同一性，该编码序列的推定蛋白质序列如SEQ ID NO.2所示。
预测的蛋白质产物的氨基酸序列表现出与流感嗜血杆菌(H.influenzae)(保藏号SWQ57431)推定的NAD(P)H硝基还原酶有43％的同一性。
鉴于酿脓链球菌的推定的NAD(P)H硝基还原酶基因与流感嗜血杆菌的该基因的相似性，本领域技术人员可以理解在其他链球菌和革兰氏阳性菌中的类似序列也可能涉及毒力。
在毒力减弱测试中，突变微生物显示出毒力减弱，其竞争指数(CI)为0.644。
实施例2鉴定另一个突变体，并克隆紧接转座子插入的核苷酸序列。
所述核苷酸序列，在核苷酸水平表现出与酿脓链球菌基因组中如SEQID NO.3所示的序列有98％的同一性。其推定的氨基酸序列如SEQ ID NO.4所示。
所述氨基酸序列表现出与变异链球菌(S.mutans)(保藏号TREMBL069155)可能的整合酶有81％的同一性。
这证明，被破坏的基因与变异链球菌可能的整合酶基因至少部分相同。然而该基因先前在酿脓链球菌中是未知的，并不认为其在毒力中起作用。
鉴于所述酿脓链球菌基因与变异链球菌可能的整合酶基因的相似性，本领域技术人员可以理解在其他链球菌和革兰氏阳性菌中的类似序列也是毒力决定子。
在毒力减弱测试中，突变微生物显示出毒力减弱，其竞争指数(CI)为0.229。
实施例3鉴定另一个突变体，并克隆紧接转座子插入的核苷酸序列。
所述核苷酸序列，在核苷酸水平表现出与酿脓链球菌基因组中如SEQID NO.5所示的序列有97％的同一性。其预测的氨基酸序列如SEQ ID NO.6所示。
所述氨基酸序列在氨基酸水平表现出与单细胞蓝细菌Synechocystis。spp(保藏号TREMBLP73511)的GlgP蛋白有37％的同一性。
这证明，被破坏的基因与Synechocystis.spp的glgP基因至少部分相同。
鉴于所述酿脓链球菌基因与Synechocystis.spp的glgP基因的相似性，本领域技术人员可以理解在其他链球菌和革兰氏阳性菌中的类似序列也是毒力决定子。
在毒力减弱测试中，突变微生物显示出毒力减弱，其竞争指数(CI)为0.011。
实施例4鉴定另一个突变体，并克隆紧接转座子插入的核苷酸序列。
所述核苷酸序列，在核苷酸水平表现出与酿脓链球菌基因组中如SEQID NO.7所示的序列有97％的同一性。其预测的氨基酸序列如SEQ ID NO.8所示。
所述氨基酸序列在氨基酸水平表现出与枯草芽孢杆菌(B.subtilis)(保藏号TREMBL034545)的BraB蛋白有35％的同一性。。
这证明，被破坏的基因与枯草芽孢杆菌的braB基因至少部分相同。
鉴于所述酿脓链球菌的braB基因与枯草芽孢杆菌的braB基因的相似性，本领域技术人员可以理解在其他链球菌和革兰氏阳性菌中的类似序列也可能涉及毒力。
在毒力减弱测试中，突变微生物显示出毒力减弱，其竞争指数(CI)为0.88。
实施例5鉴定另一个突变体，并克隆紧接转座子插入的核苷酸序列。
所述核苷酸序列，在核苷酸水平表现出与酿脓链球菌基因组中如SEQID NO.9所示的序列有99％的同一性。其预测的氨基酸序列如SEQ ID NO.10所示。
还鉴定了另一个减毒突变体，其核苷酸序列在核苷酸水平与酿脓链球菌基因组中如SEQ ID NO.11所示的序列有98％的同一性。其预测的氨基酸序列如SEQ ID NO.12所示。
第一个突变体的预测蛋白质在氨基酸水平与肺炎链球菌(S.pneumoniae)(保藏号TREMBL033703)的AdcR蛋白有53％的同一性。第二个突变体的预测蛋白质在氨基酸水平与肺炎链球菌(保藏号TREMBL087862)的AdcC蛋白有79％的同一性。
这证明，被破坏的基因与肺炎链球菌的adcR基因和adcC基因至少部分相同。adcR基因和adcC基因是肺炎链球菌中adc操纵子(包括adcR，adcC，adcB和adcA)的一部分。因此酿脓链球菌adcR和adcC突变体的毒力减弱可能是由不能表达adcR和adcC基因或其预测的下游基因(adcB和adcA同源基因)所致。先前不认为这些基因在酿脓链球菌的毒力中起作用。
鉴于所述酿脓链球菌基因与肺炎链球菌的adcR基因和adcC基因的相似性，本领域技术人员可以理解在其他链球菌和革兰氏阳性菌中的类似序列可能涉及毒力。
在毒力减弱测试中，突变微生物显示出毒力减弱，其竞争指数(CI)为0.548(adcR)和0.028(adcC)。
实施例6鉴定另一个突变体，并克隆紧接转座子插入的核苷酸序列。
所述核苷酸序列，在核苷酸水平表现出与酿脓链球菌基因组中如SEQID NO.13所示的序列有99％的同一性。其预测的氨基酸序列如SEQ ID NO.14所示。
所述氨基酸序列在氨基酸水平表现出与枯草芽孢杆菌(保藏号SWQ02170)的DNA修复蛋白radC同源物(orfB)有39％的同一性。
这证明，被破坏的基因与枯草芽孢杆菌的orfB基因至少部分相同。
鉴于所述酿脓链球菌的orfB基因与枯草芽孢杆菌的orfB基因的相似性，本领域技术人员可以理解在其他链球菌和革兰氏阳性菌中的类似序列可能涉及毒力。
在毒力减弱测试中，突变微生物显示出毒力减弱，其竞争指数(CI)为0.766。
实施例7鉴定另一个突变体，并克隆紧接转座子插入的核苷酸序列。
所述核苷酸序列，在核苷酸水平表现出与酿脓链球菌基因组中如SEQID NO.15所示的序列有98％的同一性。其预测的氨基酸序列如SEQ ID NO.16所示。
所述氨基酸序列在氨基酸水平表现出与变异链球菌(保藏号SWP29337)的生物素羧基载体蛋白(BCCP)有54％的同一性。
这证明，被破坏的基因与编码变异链球菌BCCP的基因至少部分相同。该基因先前在酿脓链球菌中是未知的，并不认为其在毒力中起作用。
鉴于所述翻译的酿脓链球菌基因与变异链球菌BCCP的相似性，本领域技术人员可以理解在其他链球菌和革兰氏阳性菌中的类似序列可能涉及毒力。
在毒力减弱测试中，突变微生物显示出毒力减弱，其竞争指数(CI)为0.044。
实施例8鉴定一系列与涉及柠檬酸发酵的基因具有序列相似性的突变体。八个突变体的核苷酸序列表现出与酿脓链球菌基因组中如SEQ ID NO.17所示的序列100％的同一性。其预测的氨基酸序列如SEQ ID NO.18所示。
所述酿脓链球菌基因的预测蛋白在氨基酸水平与大肠杆菌(E.coli)(保藏号SWP75726)的citF蛋白，柠檬酸裂合酶α链有58％的同一性。
另三个突变体的核苷酸序列表现出与酿脓链球菌基因组中的不同序列有99％的同一性。所述核苷酸序列如SEQ ID NO.19所示，其预测的氨基酸序列如SEQ ID NO.20所示。
所述氨基酸序列在氨基酸水平与大肠杆菌(保藏号SWP77770)的citE蛋白，柠檬酸裂合酶β链有55％的同一性。
另两个突变体的核苷酸序列表现出与酿脓链球菌中如SEQ ID NO.21所示的核苷酸序列有99％的同一性。其预测的氨基酸序列如SEQ ID NO.22所示。
所述氨基酸序列在氨基酸水平与大肠杆菌(保藏号SWP77618)的CitD蛋白，柠檬酸裂合酶酰基载体蛋白(柠檬酸裂解酶γ链)有46％的同一性。
鉴定了另两个突变体，其核苷酸序列表现出与酿脓链球菌中如SEQ IDNO.23所示的核苷酸序列有99％的同一性。其预测的氨基酸序列如SEQ IDNO.24所示。
所述氨基酸序列在氨基酸水平与大肠杆菌(保藏号SWP77390)的CitC蛋白，柠檬酸(pro-3s)-裂合酶(连接酶)有34％的同一性。
鉴定了另一个突变体，其核苷酸序列表现出与酿脓链球菌中如SEQ IDNO.25所示的核苷酸序列有99％的序列同一性。其预测的氨基酸序列如SEQID NO.26所示。
所述氨基酸序列在氨基酸水平与大肠杆菌(保藏号SWP77563)的CitX蛋白有37％的同一性。
鉴定了另三个突变体，其核苷酸序列表现出与酿脓链球菌中如SEQ IDNO.27所示的核苷酸序列有100％的同一性。其预测的氨基酸序列如SEQ IDNO.28所示。
所述氨基酸序列在氨基酸水平表现出与肺炎克雷伯氏菌(K.pneumoniae)(保藏号SWP13187)的OadA蛋白，草酰乙酸脱羧酶α亚基有59％的同一性。
所有上述突变体的预测蛋白质序列表现出与大肠杆菌或肺炎克雷伯氏菌中柠檬酸发酵所需的基因产物具有不同程度的同一性。
这证明，被破坏的基因与大肠杆菌或肺炎克雷伯氏菌的citF，E，D，C，X和oadA基因至少部分相同。涉及柠檬酸发酵的基因共同定位于大肠杆菌和肺炎克雷伯氏菌染色体上的单一位点。因此，酿脓链球菌突变体的毒力减弱可能是由不能表达其citFEDCX和oadA基因或下游基因所致。先前不认为这些基因在毒力中起作用。
鉴于所述酿脓链球菌基因与大肠杆菌或肺炎克雷伯氏菌中存在的那些基因的相似性，本领域技术人员可以理解在其他链球菌和革兰氏阳性菌中的类似序列可能涉及毒力。
对各citF，E，D，X和oadA的突变体测试毒力的减弱。突变微生物表现出毒力减弱，其竞争指数(CI)为0.122(citF)，0.064(citE)，0.078(citD)，0.025(citX)和0.251(oadA)。
实施例9鉴定了另一个突变体，并克隆紧接转座子插入的核苷酸序列。
所述核苷酸序列在核苷酸水平表现出与酿脓链球菌基因组中如SEQID NO.29所示的序列有98％的同一性。其预测的氨基酸序列如SEQ ID NO.30所示。
所述氨基酸序列在氨基酸水平表现出与金黄色葡萄球菌(S.aureus)(保藏号TREMBLQ9X9D7)的femB蛋白有27％的同一性。
这证明，被破坏的基因与金黄色葡萄球菌的femB基因至少部分相同。然而，该基因先前在酿脓链球菌中是未知的，并不认为其在毒力中起作用。
鉴于所述酿脓链球菌基因与金黄色葡萄球菌的femB基因的相似性，本领域技术人员可以理解在其他链球菌和革兰氏阳性菌中的类似序列可能涉及毒力。
实施例10鉴定了另一个突变体，并克隆紧接转座子插入的核苷酸序列。
所述核苷酸序列与酿脓链球菌基因组中如SEQ ID NO.31所示的序列有显著的同一性。其预测的氨基酸序列如SEQ ID NO.32所示。
在毒力减弱测试中，突变微生物显示出毒力减弱，其竞争指数(CI)为0.160。
实施例11鉴定了另一个突变体，并克隆紧接转座子插入的核苷酸序列。
所述核苷酸序列与酿脓链球菌基因组中如SEQ ID NO.33所示的序列具有100％的同一性。其预测的氨基酸序列如SEQ ID NO.34所示。
实施例12鉴定另一个突变体，并克隆紧接转座子插入的核苷酸序列。
所述核苷酸序列，在核苷酸水平与酿脓链球菌基因组中如SEQ IDNO.35所示的序列有98％的同一性。其预测的氨基酸序列如SEQ ID NO.36所示。
所述氨基酸序列在氨基酸水平表现出与枯草芽孢杆菌(保藏号SWP33116)的枯草菌素转运ATP结合蛋白有46％的同一性。
这证明，被破坏的基因与枯草芽孢杆菌的braB基因至少部分相同。
鉴于所述酿脓链球菌的基因与枯草芽孢杆菌的基因的相似性，本领域技术人员可以理解在其他链球菌和革兰氏阳性菌中的类似序列可能涉及毒力。
在毒力减弱测试中，突变微生物显示出毒力减弱，其竞争指数(CI)为0.128。
实施例13鉴定了另一个突变体，并克隆紧接转座子插入的核苷酸序列。
所述核苷酸序列与酿脓链球菌基因组中如SEQ ID NO.37所示的序列具有98％的同一性。其预测的氨基酸序列如SEQ ID NO.38所示。
实施例14鉴定另一个突变体，并克隆紧接转座子插入的核苷酸序列。
所述核苷酸序列与酿脓链球菌基因组中如SEQ ID NO.39所示的序列具有98％的同一性。其预测的氨基酸序列如SEQ ID NO.40所示。
所述氨基酸序列在氨基酸水平表现出与大肠杆菌(保藏号SWP33019)的36.9kDa假设蛋白有29％的同一性。
这证明，被破坏的基因与大肠杆菌的所述基因至少部分相同。其他类似序列可能涉及毒力。
在毒力减弱测试中，突变微生物显示出毒力减弱，其竞争指数(CI)为0.747。
实施例15鉴定另一个突变体，并克隆紧接转座子插入的核苷酸序列。
所述核苷酸序列与酿脓链球菌基因组中如SEQ ID NO.41所示的序列有99％的同一性。其预测的氨基酸序列如SEQ ID NO.42所示。
所述氨基酸序列在氨基酸水平表现出与闪烁古生球菌(A.fulgidus)(保藏号TREMBL028455)的89kDa假设蛋白有29％的同一性。
这证明，被破坏的基因与大肠杆菌的所述基因至少部分相同。其他类似序列可能涉及毒力。
在毒力减弱测试中，突变微生物显示出毒力减弱，其竞争指数(CI)为0.588。
实施例16鉴定另一个突变体，并克隆紧接转座子插入的核苷酸序列。
所述核苷酸序列与酿脓链球菌基因组中如SEQ ID NO.43所示的序列有99％的同一性。其预测的氨基酸序列如SEQ ID NO.44所示。
实施例17鉴定另一个突变体，并克隆紧接转座子插入的核苷酸序列。
所述核苷酸序列与酿脓链球菌基因组中如SEQ ID NO.45所示的序列有98％的同一性。其预测的氨基酸序列如SEQ ID NO.46所示。
实施例18鉴定另一个突变体，并克隆紧接转座子插入的核苷酸序列。
所述核苷酸序列与酿脓链球菌基因组中如SEQ ID NO.47所示的序列有97％的同一性。其预测的氨基酸序列如SEQ ID NO.48所示实施例19鉴定另一个突变体，并克隆紧接转座子插入的核苷酸序列。
所述核苷酸序列，在核苷酸水平与酿脓链球菌基因组中如SEQ IDNO.49所示的序列有98％的同一性。其预测的氨基酸序列如SEQ ID NO.50所示。
所述氨基酸序列在氨基酸水平表现出与肺炎链球菌(保藏号SWQ54955)的ciaH蛋白有47％的同一性。
这证明，被破坏的基因与肺炎链球菌的ciaH基因至少部分相同。
鉴于所述酿脓链球菌的ciaH基因与肺炎链球菌的ciaH基因的相似性，本领域技术人员可以理解在其他链球菌和革兰氏阳性菌中的类似序列可能涉及毒力。
在毒力减弱测试中，突变微生物显示出毒力减弱，其竞争指数(CI)为0.205。
实施例20鉴定另一个突变体，并克隆紧接转座子插入的核苷酸序列。
所述核苷酸序列，在核苷酸水平与酿脓链球菌基因组中如SEQ IDNO.51所示的序列有98％的同一性。其预测的氨基酸序列如SEQ ID NO.52所示。
所述氨基酸序列在氨基酸水平表现出与肺炎链球菌(保藏号TREMBLQ9ZBB1)的mucA同源蛋白有39％的同一性。
这证明，被破坏的基因与肺炎链球菌的mucA基因至少部分相同。
鉴于所述酿脓链球菌的基因与肺炎链球菌的mucA基因的相似性，本领域技术人员可以理解在其他链球菌和革兰氏阳性菌中的类似序列可能涉及毒力。
在毒力减弱测试中，突变微生物显示出毒力减弱，其竞争指数(CI)为0.547。
实施例21鉴定另一个突变体，并克隆紧接转座子插入的核苷酸序列。
所述核苷酸序列，在核苷酸水平与酿脓链球菌基因组中如SEQ IDNO.53所示的序列有98％的同一性。其预测的氨基酸序列如SEQ ID NO.54所示。
所述氨基酸序列在氨基酸水平表现出与枯草芽孢杆菌(保藏号SWP39815)的gidA蛋白有69％的同一性。
这证明，被破坏的基因与枯草芽孢杆菌的所述基因至少部分相同。
鉴于所述酿脓链球菌的基因与枯草芽孢杆菌的gidA基因的相似性，本领域技术人员可以理解在其他链球菌和革兰氏阳性菌中的类似序列可能涉及毒力。
在毒力减弱测试中，突变微生物显示出毒力减弱，其竞争指数(CI)为0.444。
实施例22鉴定另一个突变体，并克隆紧接转座子插入的核苷酸序列。
所述核苷酸序列，在核苷酸水平与酿脓链球菌基因组中如SEQ IDNO.55所示的序列有98％的同一性。其预测的氨基酸序列如SEQ ID NO.56所示。
所述氨基酸序列在氨基酸水平表现出与变异链球菌(保藏号SWQ53526)的dltA蛋白有74％的同一性。
这证明，被破坏的基因与变异链球菌的dltA基因至少部分相同。
鉴于所述酿脓链球菌的基因与变异链球菌的dltA基因的相似性，本领域技术人员可以理解在其他革兰氏阳性菌中的类似序列可能涉及毒力。
在毒力减弱测试中，突变微生物显示出毒力减弱，其竞争指数(CI)为0.205。
实施例23鉴定另一个突变体，并克隆紧接转座子插入的核苷酸序列。
所述核苷酸序列，在核苷酸水平与酿脓链球菌基因组中如SEQ IDNO.57所示的序列有98％的同一性。其预测的氨基酸序列如SEQ ID NO.58所示。
所述氨基酸序列在氨基酸水平表现出与闪烁古生球菌(保藏号SWO28538)的hmgA蛋白有41％的同一性。
这证明，被破坏的基因与闪烁古生球菌的所述基因至少部分相同。
鉴于所述酿脓链球菌的基因与闪烁古生球菌的hmgA基因的相似性，本领域技术人员可以理解在其他链球菌和革兰氏阳性菌中的类似序列可能涉及毒力。
在毒力减弱测试中，突变微生物显示出毒力减弱，其竞争指数(CI)为0.205。
实施例24鉴定第一个突变体，并克隆紧接转座子插入的核苷酸序列。
所述核苷酸序列与酿脓链球菌基因组中如SEQ ID NO.59所示的序列具有99％的同一性。其预测的氨基酸序列如SEQ ID NO.60所示。
所述氨基酸序列在氨基酸水平表现出与海栖热袍菌(T.maritima)(保藏号TREMBLQ9X1H1)的推定的JAG蛋白有34％的同一性。
这证明，被破坏的酿脓链球菌的基因与海栖热袍菌(T.maritima)的所述基因至少部分相同。在其他革兰氏阴性菌中的类似序列可能涉及毒力。
实施例25鉴定另一个突变体，并克隆紧接转座子插入的核苷酸序列。
所述核苷酸序列与酿脓链球菌基因组中如SEQ ID NO.61所示的序列具有99％的同一性。其预测的氨基酸序列如SEQ ID NO.62所示。
所述氨基酸序列在氨基酸水平表现出与猪链球菌(S.suis)(保藏号TREMBLQ9X4U3)的49.4kDa假设蛋白有49％的同一性。
这证明，被破坏的酿脓链球菌的基因与猪链球菌的所述基因至少部分相同。在其他革兰氏阴性菌中的类似序列也可能涉及毒力。
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ttaagccctt cttctattgg cttagaaggc tggcgctttg tcgttttaga caacaagcct 180attaaagaag aaatcaagcc ctttgcctgg ggagcccagt atcaactgga aacagctagt 240cactttattc ttttaatagc cgaaaaacat gcaagatacg atagccctgc tatcaaaaat 300agccttttac ggcgtggtat caaagaaggt gatggtctca acagccgcct aaaactctat 360gaatctttcc aaaaagagga catggatatg gcagataatc ctcgggcact ctttgattgg 420acagctaaac aaacctatat cgctcttggt aatatgatga tgacagctgc tcttttgggc 480attgatactt gccctattga aggctttcat tatgataagg tcaatcatat cctagctaag 540cataatgtga ttgatttaga aaaagaaggc attgctagca tgttatccct aggctatcgt 600ttgcgagatc ccaaacatgc tcaagttcgt aagcctaaag aagaagtgat ttcagtcgtt 660aaatga666<210>2<211>221<212>PRT<213>酿脓链球菌<400>2Met Asp Gln Thr Ile His His Gln Ile Gln Gln Ala Leu His Phe Arg1 5 10 15Thr Ala Val Arg Val Tyr Lys Glu Glu Lys Ile Ser Asp Glu Asp Leu20 25 30Ala Leu Ile Leu Asp Ala Ala Trp Leu Ser Pro Ser Ser Ile Gly Leu35 40 45Glu Gly Trp Arg Phe Val Val Leu Asp Asn Lys Pro Ile Lys Glu Glu50 55 60Ile Lys Pro Phe Ala Trp Gly Ala Gln Tyr Gln Leu Glu Thr Ala Ser65 70 75 80His Phe Ile Leu Leu Ile Ala Glu Lys His Ala Arg Tyr Asp Ser Pro85 90 95Ala Ile Lys Asn Ser Leu Leu Arg Arg Gly Ile Lys Glu Gly Asp Gly100 105 110Leu Asn Ser Arg Leu Lys Leu Tyr Glu Ser Phe Gln Lys Glu Asp Met115 120 125Asp Met Ala Asp Asn Pro Arg Ala Leu Phe Asp Trp Thr Ala Lys Gln130 135 140Thr Tyr Ile Ala Leu Gly Asn Met Met Met Thr Ala Ala Leu Leu Gly145 150 155 160Ile Asp Thr Cys Pro Ile Glu Gly Phe His Tyr Asp Lys Val Asn His
165 170 175Ile Leu Ala Lys His Asn Val Ile Asp Leu Glu Lys Glu Gly Ile Ala180 185 190Ser Met Leu Ser Leu Gly Tyr Arg Leu Arg Asp Pro Lys His Ala Gln195 200 205Val Arg Lys Pro Lys Glu Glu Val Ile Ser Val Val Lys210 215 220<210>3<211>1071<212>DNA<213>酿脓链球菌<400>3atgagacgcg aattattact agaaaaaatt gaaacctaca aggctatcat gccctggtat 60gttttagatt attaccaatc caaattagct gttccataca gctttaccac cttatatgag 120tatttaaaag aatacaaacg cttttttgat tggctgatgg atgctgattt aacgcaggcg 180ccaaagattg ctgatattga cttgagcacg cttgagcacc ttaccaagaa ggatttagag 240gcctttgtgc tttatttgcg ggaacgacct tctctcaaca cctattccac caaagagggg 300ctttctcaaa ccactattaa tcggaccttg tctgccttat caagccttta caagtacttg 360actgaagagg ttgaaaatga ccaaggggag ccttattttt atcggaatgt tatgaaaaaa 420gtgtcaacaa aaaagaaaaa agaaaccctg gcttccagag cggaaaatat taagcagaaa 480ctgtttttag gtgatgaaac tctagctttc ttggattatg tggataagga atatgagcaa 540aaattgtcta atcgtgccaa atcttctttc cgtaaaaata aggagaggga tttggctatt 600attgctctac tacttgcttc tggtgttcgt ttgtctgaag cagtgaatct tgatttaaaa 660gatgtcaatc taaatatgat gattatcgaa gttattcgca aaggcggaaa acgtgattca 720gtcaatgtag caggttttgc gaaaggttat ttggagtctt atttagctgt tcgtcagaga 780cgttacaagg ctgaaaaaca ggatcttgct ttctttttaa cagaataccg tggcgttcca 840aatcgaatgg atgcttctag tatagaaaag atggttggca agtactctga ggattttaaa 900attcgtgtga ctcctcacaa attgcgtcat acgctagcga caagactata tgatgctact 960aaatctcagg tgttagttag tcatcaatta ggccattcct ctactcaagt cacggatctt 1020tatacccata ttgtcaatga tgagcaaaaa aatgctttag ataaccttta a 1071<210>4<211>356<212>PRT<213>酿脓链球菌<400>4Met Arg Arg Glu Leu Leu Leu Glu Lys Ile Asp Glu Leu Lys Glu Leu1 5 10 15Met Pro Trp Tyr Val Leu Glu Tyr Tyr Gln Ser Lys Leu Thr Val Pro
20 25 30Tyr Ser Phe Thr Thr Leu Tyr Glu Tyr Leu Lys Glu Tyr Arg Arg Phe35 40 45Phe Glu Trp Leu Ile Asp Ser Gly Val Ser Asn Ala Asn Lys Leu Ala50 55 60Asp Ile Pro Leu Glu Thr Leu Glu His Leu Ser Lys Lys Asp Met Glu65 70 75 80Ser Phe Ile Leu Tyr Leu Arg Glu Arg Thr Leu Leu Asn Thr Lys Asn85 90 95Lys Arg Gln Gly Val Ser Gln Thr Thr Ile Asn Arg Thr Leu Ser Ala100 105 110Leu Ser Ser Leu Tyr Lys Tyr Leu Thr Glu Glu Val Glu Asn Ala Asp115 120 125Gly Glu Pro Tyr Phe Tyr Arg Asn Val Met Lys Lys Val Ser Thr Lys130 135 140Lys Lys Lys Glu Thr Leu Ala Ala Arg Ala Glu Asn Ile Lys Gln Lys145 150 155 160Leu Phe Leu Gly Asn Glu Thr Met Glu Phe Leu Glu Tyr Val Asp Cys165 170 175Glu Tyr Glu Gln Lys Leu Ser Lys Arg Ala Leu Ser Ser Phe Arg Lys180 185 190Asn Lys Glu Arg Asp Leu Ala Ile Ile Ala Leu Leu Leu Ala Ser Gly195 200 205Val Arg Leu Ser Glu Ala Val Asn Leu Asp Leu Lys Asp Val Asn Leu210 215 220Asn Met Met Ile Ile Glu Val Thr Arg Lys Gly Gly Lys His Asp Ser225 230 235 240Val Asn Val Ala Gly Phe Ala Lys Pro Tyr Leu Glu Asn Tyr Ile Thr245 250 255Ile Arg Arg Gly Arg Tyr Lys Ala Lys Lys Thr Asp Leu Ala Phe Phe260 265 270Leu Ser Glu Tyr Arg Gly Val Pro Asn Arg Met Asp Ala Ser Ser Ile275 280 285
Glu Lys Met Val Ala Lys Tyr Ser Gln Asp Phe Lys Ile Arg Val Thr290 295 300Pro His Lys Leu Arg His Thr Leu Ala Thr Arg Leu Tyr Asp Ala Thr305 310 315 320Lys Ser Gln Val Leu Val Ser His Gln Leu Gly His Ala Ser Thr Gln325 330 335Val Thr Asp Leu Tyr Thr His Ile Val Asn Asp Glu 6ln Lys Asn Ala340 345 350Leu Asp Lys Leu355<210>5<211>2265<212>DNA<213>酿脓链球菌<400>5atgacacgct ttacagaata tgttgaaact aaactaggaa aatcacttac gcaagccagc 60aatgaagaga tttatctatc attattaaac tttgtcaaag aagaagctag ccacaaggct 120aaaaattctg ctaaacgcaa agtttactat atctcagcag agtttttgat tggtaaatta 180ctatcaaaca acctgattaa cctaggaatt tacaaggaca tcaaagaaga attggcagct 240gctggcaagt ctatcgcaga agtcgaagat gttgaattag aaccatcact aggtaatggt 300ggtttaggac gccttgcttc atgttttatt gactctattg catctcttgg gattaatggt 360gaaggggttg gtttaaacta tcattgtggg ttgtttaagc aagtcttcaa acacaatgag 420caagaagctg agccaaactt ctggattgaa gatgactcat ggttggttcc aacagacatt 480tcttacgatg tgccttttaa gaacttcacc ttgaaatctc gtcttgatcg tattgatgtt 540ttgggttaca aacgcgacac taaaaactac cttaacttgt ttgatatcga gggcgttgat 600tacgggttaa tcaaagacgg catttctttt gataaaacgc aaattgctaa aaacttgacc 660ttgttcctct acccagacga ttctgacaaa aatggggaat tgctccgtat ttaccaacag 720tactttatgg tgtcaaatgc agcgcaatta atcattgatg aagctatcga acgtggttca 780aaccttcatg accttgcaga ctacgcttac gtgcaaatta atgacacgca tccatcaatg 840gtcatcccag aattaattcg tctcttgact gaaaaacatg gctttgactt tgatgaagcg 900gtagctgttg tgaaaaatat ggttggttac actaaccaca ctattcttgc agaagccctt 960gaaaaatggc caactgctta cttaaacgaa gtagtgccac acttggtaac catcattgaa 1020aaattggatg ctcttgttcg ttcagaagtg tctgatccag ctgttcaaat tattgacgaa 1080tcaggtcgtg tgcacatggc ccatatggat attcattttg caacaagtgt caatggggta 1140gcagcactcc acacagaaat cttgaaaaac agcgaattaa aagctttcta tgacctttac 1200ccagaaaaat tcaacaacaa aaccaacggg attactttcc gtcgttggct agaatttgct 1260aaccaagact tggctgatta cattaaagaa cttattggcg atgagtactt gactgacgca 1320acaaaattag aaaaattgat ggcctttgca gatgacaaag ctgttcatgc taaattggct 1380gaaatcaaat tcaacaacaa attagctctt aaacgttacc ttaaagacaa taaagacatt 1440gagcttgatg aacattctat tattgatacc caaatcaaac gtttccacga gtacaaacgt 1500
caacagatga atgctcttta cgtgattcac aaatatttgg aaattaaaaa aggcaacctt 1560ccaaaacgta aaatcactgt tatctttgga ggtaaagcag cgcctgctta cattattgcg 1620caagacatca ttcacttgat cctttgcttg tctgaattga ttaacaatga ccctgaagta 1680agcccatacc ttaatgtgca tctagttgaa aattacaacg tgacagtagc agagcacttg 1740attccagcaa ctgatatttc tgagcaaatt tcactagcat ccaaagaagc ttctggaact 1800ggtaatatga aattcatgct taacggtgct ttaacacttg gtacaatgga cggtgctaac 1860gtagaaatcg ctgagcttgc aggcatggag aatatctata cctttggtaa agattctgac 1920accatcatca acctttatgc gactgcttct tatgtagcaa aagattacta tgataaccac 1980cctgctatta aagcagcagt gaactttatt atcagtccag aattgctagc atttggcaac 2040gaagaacgtc ttgatcgtct ttataaagaa ttgatttcaa aagactggtt catgactttg 2100attgaccttg aagagtacat tgaagtgaaa gaaaaaatgt tagcagacta tgaagaccaa 2160gatttatgga tgacaaaagt ggtccataac atcgcaaaag ctggattctt ctcatctgac 2220cgtaccattg agcagtataa cgaagatatt tggcattcac gataa 2265<210>6<211>754<212>PRT<213>酿脓链球菌<400>6Met Thr Arg Phe Thr Glu Tyr Val Glu Thr Lys Leu Gly Lys Ser Leu1 5 10 15Thr Gln Ala Ser Asn Glu Glu Ile Tyr Leu Ser Leu Leu Asn Phe Val20 25 30Lys Glu Glu Ala Ser His Lys Ala Lys Asn Ser Ala Lys Arg Lys Val35 40 45Tyr Tyr Ile Ser Ala Glu Phe Leu Ile Gly Lys Leu Leu Ser Asn Asn50 55 60Leu Ile Asn Leu Gly Ile Tyr Lys Asp Ile Lys Glu Glu Leu Ala Ala65 70 75 80Ala Gly Lys Ser Ile Ala Glu Val Glu Asp Val Glu Leu Glu Pro Ser85 90 95Leu Gly Asn Gly Gly Leu Gly Arg Leu Ala Ser Cys Phe Ile Asp Ser100 105 110Ile Ala Ser Leu Gly Ile Asn Gly Glu Gly Val Gly Leu Asn Tyr His115 120 125Cys Gly Leu Phe Lys Gln Val Phe Lys His Asn Glu Gln Glu Ala Glu130 135 140Pro Asn Phe Trp Ile Glu Asp Asp Ser Trp Leu Val Pro Thr Asp Ile
145 150 155 160Ser Tyr Asp Val Pro Phe Lys Asn Phe Thr Leu Lys Ser Arg Leu Asp165 170 175Arg Ile Asp Val Leu Gly Tyr Lys Arg Asp Thr Lys Asn Tyr Leu Asn180 185 190Leu Phe Asp Ile Glu Gly Val Asp Tyr Gly Leu Ile Lys Asp Gly Ile195 200 205Ser Phe Asp Lys Thr Gln Ile Ala Lys Asn Leu Thr Leu Phe Leu Tyr210 215 220Pro Asp Asp Ser Asp Lys Asn Gly Glu Leu Leu Arg Ile Tyr Gln Gln225 230 235 240Tyr Phe Met Val Ser Asn Ala Ala Gln Leu Ile Ile Asp Glu Ala Ile245 250 255Glu Arg Gly Ser Asn Leu His Asp Leu Ala Asp Tyr Ala Tyr Val Gln260 265 270Ile Asn Asp Thr His Pro Ser Met Val Ile Pro Glu Leu Ile Arg Leu275 280 285Leu Thr Glu Lys His Gly Phe Asp Phe Asp Glu Ala Val Ala Val Val290 295 300Lys Asn Met Val Gly Tyr Thr Asn His Thr Ile Leu Ala Glu Ala Leu305 310 315 320Glu Lys Trp Pro Thr Ala Tyr Leu Asn Glu Val Val Pro His Leu Val325 330 335Thr Ile Ile Glu Lys Leu Asp Ala Leu Val Arg Ser Glu Val Ser Asp340 345 350Pro Ala Val Gln Ile Ile Asp Glu Ser Gly Arg Val His Met Ala His355 360 365Met Asp Ile His Phe Ala Thr Ser Val Asn Gly Val Ala Ala Leu His370 375 380Thr Glu Ile Leu Lys Asn Ser Glu Leu Lys Ala Phe Tyr Asp Leu Tyr385 390 395 400Pro Glu Lys Phe Asn Asn Lys Thr Asn Gly Ile Thr Phe Arg Arg Trp405 410 415
Leu Glu Phe Ala Asn Gln Asp Leu Ala Asp Tyr Ile Lys Glu Leu Ile420 425 430Gly Asp Glu Tyr Leu Thr Asp Ala Thr Lys Leu Glu Lys Leu Met Ala435 440 445Phe Ala Asp Asp Lys Ala Val His Ala Lys Leu Ala Glu Ile Lys Phe450 455 460Asn Asn Lys Leu Ala Leu Lys Arg Tyr Leu Lys Asp Asn Lys Asp Ile465 470 475 480Glu Leu Asp Glu His Ser Ile Ile Asp Thr Gln Ile Lys Arg Phe His485 490 495Glu Tyr Lys Arg Gln Gln Met Asn Ala Leu Tyr Val Ile His Lys Tyr500 505 510Leu Glu Ile Lys Lys Gly Asn Leu Pro Lys Arg Lys Ile Thr Val Ile515 520 525Phe Gly Gly Lys Ala Ala Pro Ala Tyr Ile Ile Ala Gln Asp Ile Ile530 535 540His Leu Ile Leu Cys Leu Ser Glu Leu Ile Asn Asn Asp Pro Glu Val545 550 555 560Ser Pro Tyr Leu Asn Val His Leu Val Glu Asn Tyr Asn Val Thr Val565 570 575Ala Glu His Leu Ile Pro Ala Thr Asp Ile Ser Glu Gln Ile Ser Leu580 585 590Ala Ser Lys Glu Ala Ser Gly Thr Gly Asn Met Lys Phe Met Leu Asn595 600 605Gly Ala Leu Thr Leu Gly Thr Met Asp Gly Ala Asn Val Glu Ile Ala610 615 620Glu Leu Ala Gly Met Glu Asn Ile Tyr Thr Phe Gly Lys Asp Ser Asp625 630 635 640Thr Ile Ile Asn Leu Tyr Ala Thr Ala Ser Tyr Val Ala Lys Asp Tyr645 650 655Tyr Asp Asn His Pro Ala Ile Lys Ala Ala Val Asn Phe Ile Ile Ser660 665 670
Pro Glu Leu Leu Ala Phe Gly Asn Glu Glu Arg Leu Asp Arg Leu Tyr675 680 685Lys Glu Leu Ile Ser Lys Asp Trp Phe Met Thr Leu Ile Asp Leu Glu690 695 700Glu Tyr Ile Glu Val Lys Glu Lys Met Leu Ala Asp Tyr Glu Asp Gln705 710 715 720Asp Leu Trp Met Thr Lys Val Val His Asn Ile Ala Lys Ala Gly Phe725 730 735Phe Ser Ser Asp Arg Thr Ile Glu Gln Tyr Asn Glu Asp Ile Trp His740 745 750Ser Arg<210>7<211>1371<212>DNA<213>酿脓链球菌<400>7atgaaacaaa aaaatgtata tatcgtcatt ggattcatgc tatttgcgct attttttgga 60gcagcaaacc tcatttaccc agctttttta ggcatctact caggtcatca gattctatgg 120tctatcattg gtttttgttt aactggtgtc tccttgcctt tactcggtgt cattgctgtt 180gctaaatctg gatcaggcga tgttgaaagt ttggcacgcc ccatctctaa atggtatgca 240atcttctatt cttccatttt gtatttatct attggcccat tttttgctat tccaagaaca 300ggagccactt ctttttcagt cggtatcgct cctatcttag gagataatac aaccaataaa 360gctatttatg ctatactatt ttttggtctg tcctacttcc ttgctatcaa acctagtaaa 420ctagctgaaa atatcggaaa atttttaacg ccaacgttgt tagttgttat ttctattttg 480gttatcgcgt cctttgtcca tcctgctgga aattacggtg atgcttttaa cgctggggtc 540ggtgttaata atgcctttaa agattttcct tttatagcag gattaattca aggttatggc 600actatggatg cactagcttc tcttgttttt gctattttag tcattgaggc taccaaacaa 660tttggcgcta agacggacaa agaaatgacc aaaataacac ttatttctgg ggctattgcc 720attttgctat tagcacttgt ctatatcttt gtcggtcgta ttggagcaac atcacaatca 780ttatttcctt ttattgatgg cagctttacc cttcatggta atccagttaa tggcggtcaa 840atcttaagtc atgcttctcg tttttaccta ggtggcatcg gacaagcatt tctagctgtt 900gtgattttcc tggcctgtct aaccacttca acaggcttaa tcacgtcaag tgctgaatac 960ttccataaat tagtgcctgc tttatctcat attgcttggg caactatctt tactttacta 1020tcagctttct tttattttgg tggcttatca gtcattatca actggtcagc tcctgtttta 1080ttccttttat acccattaac agtcgattta attttccttg ttttggcaca aaaatgcttc 1140aataatgatc ctattgtcta tcgaactaca attggtctaa cctttattcc tgccatattt 1200gatgcactcc taacactatc acaaatgact ggattatttc atttaccaga agccgttgta 1260acttttttcc aaaaaactgt tccactaggg caattctcaa tgggatggat tatctttgct 1320gctattggtt ttttaatagg gcttatacta agtaaaacga agaaaagcta a 1371
<210>8<211>456<212>PRT<213>酿脓链球菌<400>8Met Lys Gln Lys Asn Val Tyr Ile Val Ile Gly Phe Met Leu Phe Ala1 5 10 15Leu Phe Phe Gly Ala Ala Asn Leu Ile Tyr Pro Ala Phe Leu Gly Ile20 25 30Tyr Ser Gly His Gln Ile Leu Trp Ser Ile Ile Gly Phe Cys Leu Thr35 40 45Gly Val Ser Leu Pro Leu Leu Gly Val Ile Ala Val Ala Lys Ser Gly50 55 60Ser Gly Asp Val Glu Ser Leu Ala Arg Pro Ile Ser Lys Trp Tyr Ala65 70 75 80Ile Phe Tyr Ser Ser Ile Leu Tyr Leu Ser Ile Gly Pro Phe Phe Ala85 90 95Ile Pro Arg Thr Gly Ala Thr Ser Phe Ser Val Gly Ile Ala Pro Ile100 105 110Leu Gly Asp Asn Thr Thr Asn Lys Ala Ile Tyr Ala Ile Leu Phe Phe115 120 125Gly Leu Ser Tyr Phe Leu Ala Ile Lys Pro Ser Lys Leu Ala Glu Asn130 135 140Ile Gly Lys Phe Leu Thr Pro Thr Leu Leu Val Val Ile Ser Ile Leu145 150 155 160Val Ile Ala Ser Phe Val His Pro Ala Gly Asn Tyr Gly Asp Ala Phe165 170 175Asn Ala Gly Val Gly Val Asn Asn Ala Phe Lys Asp Phe Pro Phe Ile180 185 190Ala Gly Leu Ile Gln Gly Tyr Gly Thr Met Asp Ala Leu Ala Ser Leu195 200 205Val Phe Ala Ile Leu Val Ile Glu Ala Thr Lys Gln Phe Gly Ala Lys210 215 220
Thr Asp Lys Glu Met Thr Lys Ile Thr Leu Ile Ser Gly Ala Ile Ala225 230 235 240Ile Leu Leu Leu Ala Leu Val Tyr Ile Phe Val Gly Arg Ile Gly Ala245 250 255Thr Ser Gln Ser Leu Phe Pro Phe Ile Asp Gly Ser Phe Thr Leu His260 265 270Gly Asn Pro Val Asn Gly Gly Gln Ile Leu Ser His Ala Ser Arg Phe275 280 285Tyr Leu Gly Gly Ile Gly Gln Ala Phe Leu Ala Val Val Ile Phe Leu290 295 300Ala Cys Leu Thr Thr Ser Thr Gly Leu Ile Thr Ser Ser Ala Glu Tyr305 310 315 320Phe His Lys Leu Val Pro Ala Leu Ser His Ile Ala Trp Ala Thr Ile325 330 335Phe Thr Leu Leu Ser Ala Phe Phe Tyr Phe Gly Gly Leu Ser Val Ile340 345 350Ile Asn Trp Ser Ala Pro Val Leu Phe Leu Leu Tyr Pro Leu Thr Val355 360 365Asp Leu Ile Phe Leu Val Leu Ala Gln Lys Cys Phe Asn Asn Asp Pro370 375 380Ile Val Tyr Arg Thr Thr Ile Gly Leu Thr Phe Ile Pro Ala Ile Phe385 390 395 400Asp Ala Leu Leu Thr Leu Ser Gln Met Thr Gly Leu Phe His Leu Pro405 410 415Glu Ala Val Val Thr Phe Phe Gln Lys Thr Val Pro Leu Gly Gln Phe420 425 430Ser Met Gly Trp Ile Ile Phe Ala Ala Ile Gly Phe Leu Ile Gly Leu435 440 445Ile Leu Ser Lys Thr Lys Lys Ser450 455<210>9
<211>441<212>DNA<213>酿脓链球菌<400>9atggggattt tagaaaaaaa acttgataac ttagtaaata ctattttatt aaaagcagaa 60aatcagcatg agttattatt tggagcttgt caaagtgacg ttaagcttac taatacgcaa 120gaacatattt taatgttact atctcagcaa cgtctcacta atacagattt ggctaaggca 180ttaaatatta gtcaggcggc agtaactaag gctatcaaga gtttggtcaa acaagacatg 240ttagcaggaa ctaaggatac ggttgatgct agggtgactt attttgaatt aaccgagtta 300gctaagccta ttgcgtcaga acatacccat catcatgatg aaaccttaaa tgtttacaac 360cgtttattac aaaaattctc cgcgaaagaa ttagagattg tagataagtt tgtaacagtt 420tttgctgagg aattagaagg g 441<210>10<211>147<212>PRT<213>酿脓链球菌<400>10Met Gly Ile Leu Glu Lys Lys Leu Asp Asn Leu Val Asn Thr Ile Leu1 5 10 15Leu Lys Ala Glu Asn Gln His Glu Leu Leu Phe Gly Ala Cys Gln Ser20 25 30Asp Val Lys Leu Thr Asn Thr Gln Glu His Ile Leu Met Leu Leu Ser35 40 45Gln Gln Arg Leu Thr Asn Thr Asp Leu Ala Lys Ala Leu Asn Ile Ser50 55 60Gln Ala Ala Val Thr Lys Ala Ile Lys Ser Leu Val Lys Gln Asp Met65 70 75 80Leu Ala Gly Thr Lys Asp Thr Val Asp Ala Arg Val Thr Tyr Phe Glu85 90 95Leu Thr Glu Leu Ala Lys Pro Ile Ala Ser Glu His Thr His His His100 105 110Asp Glu Thr Leu Asn Val Tyr Asn Arg Leu Leu Gln Lys Phe Ser Ala115 120 125Lys Glu Leu Glu Ile Val Asp Lys Phe Val Thr Val Phe Ala Glu Glu130 135 140Leu Glu Gly
145<210>11<211>815<212>DNA<213>酿脓链球菌<400>11atgcttgata ttttattcta tgatttcatg caacgggcgg taatggcggt agttgccatt 60agtatttttg ctccgatttt aggtattttc cttattttac gtcgtcaaag tttgatgagc 120gataccctta gtcatgtttc tttggctggg gtagcgcttg gggtagtcct tggtatttca 180ccaaccatca ctactattat tgttgtggtt ttagctgcta ttttgttaga atacctgcgt 240gtagtttaca aacactacat ggagatttca acggcgattt tgatgtcact tggcttggcc 300ctatctctga ttattatgag taagtcgcat agttcatcaa gcatgagttt agaacaatac 360ctttttggat cgatcatcac gattagtatg gaacaagttg tcgccttgtt tgctattgct 420gcgattattt taatcttgac cgttctcttc attagaccga tgtacattct gacctttgat 480gaagatactg cttttgtaga tggtttgccc gttcgcttga tgtctgttct attcaatatc 540gtcactgggg ttgctattgc tttgaccatt ccagcagcag gagcactttt ggtttctacc 600attatggtct tgccagcaag tatcgcaatg agattgggta aaaactttaa aacagttatc 660ttactgggaa ttgtcatcgg ttttagcggt atgttatctg gtattttctt atcttatttc 720tttgaaacgc cagctagtgc cactattacc atgattttca ttagtatttt cctcttagtt 780agtctaggtg gaatgcttaa aaaacggtta tttaa815<210>12<211>239<212>PRT<213>酿脓链球菌<400>12Met Arg Tyr Ile Ser Val Lys Asn Leu Ser Phe Gln Tyr Glu Ser Glu1 5 10 15Pro Val Leu Glu Gly Ile Thr Tyr His Leu Asp Ser Gly Glu Phe Val20 25 30Thr Met Thr Gly Glu Asn Gly Ala Ala Lys Ser Thr Leu Ile Lys Ala35 40 45Thr Leu Gly Ile Leu Gln Pro Lys Ala Gly Arg Val Thr Ile Ala Lys50 55 60Lys Asn Lys Asp Gly Lys Gln Leu Arg Ile Ala Tyr Leu Pro Gln Gln65 70 75 80Val Ala Ser Phe Asn Ala Gly Phe Pro Ser Thr Val Tyr Glu Phe Val85 90 95
Lys Ser Gly Arg Tyr Pro Arg Ser Gly Trp Phe Arg His Leu Asn Lys100 105 110His Asp Glu Glu His Val Gln Ala Ser Leu Glu Ala Val Gly Met Trp115 120 125Glu Asn Arg His Lys Arg Ile Gly Ser Leu Ser Gly Gly Gln Lys Gln130 135 140Arg Val Val Ile Ala Arg Met Phe Ala Ser Asp Pro Asp Ile Phe Val145 150 155 160Leu Asp Glu Pro Thr Thr Gly Met Asp Ser Gly Thr Thr Asp Thr Phe165 170 175Tyr Glu Leu Met His His Ser Ala His Gln His Gly Lys Ser Val Leu180 185 190Met Ile Thr His Asp Pro Glu Glu Val Lys Ala Tyr Ala Asp Arg Asn195 200 205Ile His Leu Val Arg Asn Gln Lys Leu Pro Trp Arg Cys Phe Asn Ile210 215 220His Glu Ala Glu Thr Asp Asp Glu Lys Gly Gly His Gly His Ala225 230 235<210>13<211>681<212>DNA<213>酿脓链球菌<400>13atgtattcta taaaatgtga tgataataaa gccatgccaa gagaacgttt gatgcgacta 60ggagcagagt ctctaagtaa tcaagaatta ttagcaattt tattacgaac aggtaataaa 120gaaaagcatg tcttagagct gtcatcctat cttttatcgc atttagacag tctggcagat 180tttaaaaaga tgtctttgca agaattacaa catttggcag gtataggaaa agttaaagcg 240attgaaatta aagctatgat tgagttggtt tcccgaattt tagcgacaga taagacatta 300actgatagcg tattaaccag tgttcaggtc gctgaaaaaa tgatggcagc tttaggagat 360aaaaaacaag agcatttagt cgtattgtat ttagataatc aaaatcgtat tattgaagaa 420aaaactattt ttattgggac tgtccgacgt tcacttgcag aaccaagaga aattttatac 480tatgcctgta aaaatatggc gactagtctc attgttattc ataatcatcc ttcaggaaat 540attgaaccta gttctaacga ttattgcttt actgaaaaaa taaaacgatc atgtgaagat 600ttaggcatta tctgtctaga tcacattatc gttagctata aagattatta tagttttcga 660gaaaaatcaa ccctttttta a 681
<210>14<211>226<212>PRT<213>酿脓链球菌<400>14Met Tyr Ser Ile Lys Cys Asp Asp Asn Lys Ala Met Pro Arg Glu Arg1 5 10 15Leu Met Arg Leu Gly Ala Glu Ser Leu Ser Asn Gln Glu Leu Leu Ala20 25 30Ile Leu Leu Arg Thr Gly Asn Lys Glu Lys His Val Leu Glu Leu Ser35 40 45Ser Tyr Leu Leu Ser His Leu Asp Ser Leu Ala Asp Phe Lys Lys Met50 55 60Ser Leu Gln Glu Leu Gln His Leu Ala Gly Ile Gly Lys Val Lys Ala65 70 75 80Ile Glu Ile Lys Ala Met Ile Glu Leu Val Ser Arg Ile Leu Ala Thr85 90 95Asp Lys Thr Leu Thr Asp Ser Val Leu Thr Ser Val Gln Val Ala Glu100 105 110Lys Met Met Ala Ala Leu Gly Asp Lys Lys Gln Glu His Leu Val Val115 120 125Leu Tyr Leu Asp Asn Gln Asn Arg Ile Ile Glu Glu Lys Thr Ile Phe130 135 140Ile Gly Thr Val Arg Arg Ser Leu Ala Glu Pro Arg Glu Ile Leu Tyr145 150 155 160Tyr Ala Cys Lys Asn Met Ala Thr Ser Leu Ile Val Ile His Asn His165 170 175Pro Ser Gly Asn Ile Glu Pro Ser Ser Asn Asp Tyr Cys Phe Thr Glu180 185 190Lys Ile Lys Arg Ser Cys Glu Asp Leu Gly Ile Ile Cys Leu Asp His195 200 205Ile Ile Val Ser Tyr Lys Asp Tyr Tyr Ser Phe Arg Glu Lys Ser Thr210 215 220
Leu Phe225<210>15<211>410<212>DNA<213>酿脓链球菌<400>15atgatgttac gaaaatttaa aattaccatt gacggtaaag agtatcttgt agaaatggaa 60gaaatcggtg ctcctgccca agcagctgcc cccgctcaac caatatccac tccagtacct 120gtccctactg aagcaagccc acaagtggag gaagcgcaag caccacagcc agtagctgca 180gcgggagcgg atgccattcc atcaccaatg cctggaacca tcttaaaagt cttagtagca 240gtgggagacc aagtaactga aaatcagcca ctattgattt tagaagccat gaagatggaa 300aatgagattg tggcctcatc agcaggaacc attacagcta tccacgtcgg tccaggtcaa 360gtggtcaatc ctggtgatgg tctcattaca attggttaat agtactataa410<210>16<211>134<212>PRT<213>酿脓链球菌<400>16Met Met Leu Arg Lys Phe Lys Ile Thr Ile Asp Gly Lys Glu Tyr Leu1 5 10 15Val Glu Met Glu Glu Ile Gly Ala Pro Ala Gln Ala Ala Ala Pro Ala20 25 30Gln Pro Ile Ser Thr Pro Val Pro Val Pro Thr Glu Ala Ser Pro Gln35 40 45Val Glu Glu Ala Gln Ala Pro Gln Pro Val Ala Ala Ala Gly Ala Asp50 55 60Ala Ile Pro Ser Pro Met Pro Gly Thr Ile Leu Lys Val Leu Val Ala65 70 75 80Val Gly Asp Gln Val Thr Glu Asn Gln Pro Leu Leu Ile Leu Glu Ala85 90 95Met Lys Met Glu Asn Glu Ile Val Ala Ser Ser Ala Gly Thr Ile Thr100 105 110Ala Ile His Val Gly Pro Gly Gln Val Val Asn Pro Gly Asp Gly Leu115 120 125
Ile Thr Ile Gly Tyr Tyr130<210>17<211>1533<212>DNA<213>酿脓链球菌<400>17atggtaacaa ataaactcgg tagagatatt cctcaaccat acgccgacca atacggtgtc 60tttgaaggag aactcgcaaa tatcaaacag tatgacgaat caagtcgccg tattaaacca 120gttaagcctg gagattctaa attactagga tctgttcgtg aagcgattga aaaaacaggt 180ttaacagatg gcatgaccat ttctttccac caccatttcc gtgaagggga tttcattatg 240aatatggtct tggaggaaat tgccaaaatg ggcattaaaa acctgtctat tgccccaagt 300tccatcgcta atgtacatga gcctttgatt gatcacatca aaaatggtgt ggtcactaac 360atcacttcat ctggtcttcg tgacaaagta ggggcagcca tctcagaagg actaatggaa 420aatcctgtgg ttattcgctc ccatggtggt cgcgctcgtg ccattgctag tggggatatc 480catattgatg ttgcctttct gggcgcccca agttcagatg cttacggaaa tgttaatggg 540acaaaaggga aagcaacctg tggttctttg ggctatgcca tgattgatgc caaatatgcg 600gatcaggtgg ttatcttgac agataatttg gttccttatc ctaatacccc aatcagcatt 660cctcaaacag atgttgacta tgtggtaaca gtggatgcta tcggagatcc tcaaggaatc 720gccaaagggg caactcgttt tacgaaaaat cctaaagaac tcttaattgc agaatacgcc 780gctaaagtaa tcaccaactc tccttatttt aaagaaggat tctctttcca aactggaaca 840ggtggcgctt ctttggcagt aacccgtttc atgcgtgaag ctatgattaa agaaaatatc 900aaagctagct ttgctcttgg tggtattacc aatgctatgg tggagttgct cgaagaagaa 960ctggttgaaa aaattcttga tgtccaagac tttgatcacc catcagctgt ttctcttggt 1020aagcatgctg aacattatga aattgatgcc aacatgtatg cctcaccttt gagcaagggt 1080gctgttatca atcaattaga cacttgtatt ttatcagccc ttgaagttga tactaacttc 1140aatgttaatg tgatgacagg atctgacggc gtgattcgtg gcgcttctgg aggacactgc 1200gacactgcct ttgcggctaa gatgagtttg gttatttcac cacttatccg cggacgcatc 1260ccaacttttg tagatgaggt taatacggtc attacaccag gaacaagtgt cgatgtgatc 1320gtcacagaag tgggaattgc cattaaccca aatcgtcaag acttagtaga ccatttcaaa 1380tccctcaatg tgccacaatt tagtattgag gagctaaaag agaaggctta cgccatcgtt 1440ggcacacctg agcgtattca atatggtgat aaggttgttg ctcttattga ataccgtgac 1500ggtagcctca tggatgtggt ttacaatgtg taa 1533<210>18<211>510<212>PRT<213>酿脓链球菌<400>18Met Val Thr Asn Lys Leu Gly Arg Asp Ile Pro Gln Pro Tyr Ala Asp1 5 10 15
Gln Tyr Gly Val Phe Glu Gly Glu Leu Ala Asn Ile Lys Gln Tyr Asp20 25 30Glu Ser Ser Arg Arg Ile Lys Pro Val Lys Pro Gly Asp Ser Lys Leu35 40 45Leu Gly Ser Val Arg Glu Ala Ile Glu Lys Thr Gly Leu Thr Asp Gly50 55 60Met Thr Ile Ser Phe His His His Phe Arg Glu Gly Asp Phe Ile Met65 70 75 80Asn Met Val Leu Glu Glu Ile Ala Lys Met Gly Ile Lys Asn Leu Ser85 90 95Ile Ala Pro Ser Ser Ile Ala Asn Val His Glu Pro Leu Ile Asp His100 105 110Ile Lys Asn Gly Val Val Thr Asn Ile Thr Ser Ser Gly Leu Arg Asp115 120 125Lys Val Gly Ala Ala Ile Ser Glu Gly Leu Met Glu Asn Pro Val Val130 135 140Ile Arg Ser His Gly Gly Arg Ala Arg Ala Ile Ala Ser Gly Asp Ile145 150 155 160His Ile Asp Val Ala Phe Leu Gly Ala Pro Ser Ser Asp Ala Tyr Gly165 170 175Asn Val Asn Gly Thr Lys Gly Lys Ala Thr Cys Gly Ser Leu Gly Tyr180 185 190Ala Met Ile Asp Ala Lys Tyr Ala Asp Gln Val Val Ile Leu Thr Asp195 200 205Asn Leu Val Pro Tyr Pro Asn Thr Pro Ile Ser Ile Pro Gln Thr Asp210 215 220Val Asp Tyr Val Val Thr Val Asp Ala Ile Gly Asp Pro Gln Gly Ile225 230 235 240Ala Lys Gly Ala Thr Arg Phe Thr Lys Asn Pro Lys Glu Leu Leu Ile245 250 255Ala Glu Tyr Ala Ala Lys Val Ile Thr Asn Ser Pro Tyr Phe Lys Glu260 265 270Gly Phe Ser Phe Gln Thr Gly Thr Gly Gly Ala Ser Leu Ala Val Thr
275 280 285Arg Phe Met Arg Glu Ala Met Ile Lys Glu Asn Ile Lys Ala Ser Phe290 295 300Ala Leu Gly Gly Ile Thr Asn Ala Met Val Glu Leu Leu Glu Glu Glu305 310 315 320Leu Val Glu Lys Ile Leu Asp Val Gln Asp Phe Asp His Pro Ser Ala325 330 335Val Ser Leu Gly Lys His Ala Glu His Tyr Glu Ile Asp Ala Asn Met340 345 350Tyr Ala Ser Pro Leu Ser Lys Gly Ala Val Ile Asn Gln Leu Asp Thr355 360 365Cys Ile Leu Ser Ala Leu Glu Val Asp Thr Asn Phe Asn Val Asn Val370 375 380Met Thr Gly Ser Asp Gly Val Ile Arg Gly Ala Ser Gly Gly His Cys385 390 395 400Asp Thr Ala Phe Ala Ala Lys Met Ser Leu Val Ile Ser Pro Leu Ile405 410 415Arg Gly Arg Ile Pro Thr Phe Val Asp Glu Val Asn Thr Val Ile Thr420 425 430Pro Gly Thr Ser Val Asp Val Ile Val Thr Glu Val Gly Ile Ala Ile435 440 445Asn Pro Asn Arg Gln Asp Leu Val Asp His Phe Lys Ser Leu Asn Val450 455 460Pro Gln Phe Ser Ile Glu Glu Leu Lys Glu Lys Ala Tyr Ala Ile Val465 470 475 480Gly Thr Pro Glu Arg Ile Gln Tyr Gly Asp Lys Val Val Ala Leu Ile485 490 495Glu Tyr Arg Asp Gly Ser Leu Met Asp Val Val Tyr Asn Val500 505 510<210>19<211>888<212>DNA
<213>酿脓链球菌<400>19atggaacgtt taagaagaac aatgatgttt gtgcctggtg ccaatgcagc catgcttcga 60gatgctcctt tatttggcgc tgattcaatc atgtttgact tggaagattc tgtttcactc 120aaagaaaaag acacctctag agctctcgtt cattttgcgc ttaaaacttt tgattattca 180agcgttgaaa cggttgttcg tgtgaatggt cttgattctt gtggggcttt agacatcgaa 240gctgttgttt tggcaggtgt caacgtgatt cgtcttccaa aaacagagac tgctcaagat 300attattgatg tggaggctgt tattgaacgt gtcgaacgcg agaacagcat tgaagttggt 360cgcacacgta tgatggcagc cattgaatca gccgaaggtg tcctaaatgc tcgtgagatt 420gccaaagctt ctaagcgctt gattggtatt gctcttggag cagaagacta tgtcacgaat 480atgaaaacgc gtcgttaccc agatggtcaa gaattattct ttgctcgtag catgatttta 540cacgctgctc gtgctgctgg aattgctgcc attgatactg tttattctga tgtcaataat 600accgaagggt tccaaaacga agttcgcatg atcaaacagt taggatttga tggtaaatcg 660gtcatcaacc ctcgccaaat tcctctggtc aatgagattt ataccccaac aaaaaaagaa 720attgaccatg ccaaacaagt catctgggca attcgtgaag ctgaaagcaa aggctctggc 780gttatttcct taaatggaaa aatggttgat aaaccaatcg ttgaacgtgc agaacgtgtg 840attgccctag caacagcagc aggtgtttta tctgaggagg atatttaa 888<210>20<211>295<212>PRT<213>酿脓链球菌<400>20Met Glu Arg Leu Arg Arg Thr Met Met Phe Val Pro Gly Ala Asn Ala1 5 10 15Ala Met Leu Arg Asp Ala Pro Leu Phe Gly Ala Asp Ser Ile Met Phe20 25 30Asp Leu Glu Asp Ser Val Ser Leu Lys Glu Lys Asp Thr Ser Arg Ala35 40 45Leu Val His Phe Ala Leu Lys Thr Phe Asp Tyr Ser Ser Val Glu Thr50 55 60Val Val Arg Val Asn Gly Leu Asp Ser Cys Gly Ala Leu Asp Ile Glu65 70 75 80Ala Val Val Leu Ala Gly Val Asn Val Ile Arg Leu Pro Lys Thr Glu85 90 95Thr Ala Gln Asp Ile Ile Asp Val Glu Ala Val Ile Glu Arg Val Glu100 105 110Arg Glu Asn Ser Ile Glu Val Gly Arg Thr Arg Met Met Ala Ala Ile115 120 125
Glu Ser Alg Glu Gly Val Leu Asn Ala Arg Glu Ile Ala Lys Ala Ser130 135 140Lys Arg Leu Ile Gly Ile Ala Leu Gly Ala Glu Asp Tyr Val Thr Asn145 150 155 160Met Lys Thr Arg Arg Tyr Pro Asp Gly Gln Glu Leu Phe Phe Ala Arg165 170 175Ser Met Ile Leu His Ala Ala Arg Ala Ala Gly Ile Ala Ala Ile Asp180 185 190Thr Val Tyr Ser Asp Val Asn Asn Thr Glu Gly Phe Gln Asn Glu Val195 200 205Arg Met Ile Lys Gln Leu Gly Phe Asp Gly Lys Ser Val Ile Asn Pro210 215 220Arg Gln Ile Pro Leu Val Asn Glu Ile Tyr Thr Pro Thr Lys Lys Glu225 230 235 240Ile Asp His Ala Lys Gln Val Ile Trp Ala Ile Arg Glu Ala Glu Ser245 250 255Lys Gly Ser Gly Val Ile Ser Leu Asn Gly Lys Met Val Asp Lys Pro260 265 270Ile Val Glu Arg Ala Glu Arg Val Ile Ala Leu Ala Thr Ala Ala Gly275 280 285Val Leu Ser Glu Glu Asp Ile290 295<210>21<211>309<212>DNA<213>酿脓链球菌<400>21atggatatta aacaaactgc cgttgctggt tcacttgaat caagtgacct aatgattaca 60gtatccccta atgacgagca aaccattaca ataaccctag acagtagtgt tgaaaaacaa 120tttggcaatc acattcgtca actcattcat caaaccctag tgaatttgaa ggtgacggct 180gctaaagtag aggctgttga taaaggtgca ttagattgca ccattcaagc gagaaccatc 240gcagctgttc atcgcgctgc tggtattgac caatacgatt ggaaggagat tgactcatgg 300aacgtttaa 309
<210>22<211>102<212>PRT<213>酿脓链球菌<400>22Met Asp Ile Lys Gln Thr Ala Val Ala Gly Ser Leu Glu Ser Ser Asp1 5 10 15Leu Met Ile Thr Val Ser Pro Asn Asp Glu Gln Thr Ile Thr Ile Thr20 25 30Leu Asp Ser Ser Val Glu Lys Gln Phe Gly Asn His Ile Arg Gln Leu35 40 45Ile His Gln Thr Leu Val Ash Leu Lys Val Thr Ala Ala Lys Val Glu50 55 60Ala Val Asp Lys Gly Ala Leu Asp Cys Thr Ile Gln Ala Arg Thr Ile65 70 75 80Ala Ala Val His Arg Ala Ala Gly Ile Asp Gln Tyr Asp Trp Lys Glu85 90 95Ile Asp Ser Trp Asn Val100<210>23<211>1053<212>DNA<213>酿脓链球菌<400>23atgccttact acactatttc aaaagtcttt ccttcagata aaacgacaat ggctagtgta 60aagaacctgc ttcatcaaga aggtattcgt ttggatgctc atttagatta tacttgtgcc 120atcatgaatg cgcaaaatga tgtgattgct accggttctt actttggaaa tagcttgcgc 180tgtctttgcg tatccagtgc ctatcaaggt gaaggacttc ttaataggat tgtgagtcat 240ctcattgatg aagaatatgc ccttggcaac tatcatcttt ttgtttatac gaagacctct 300tctgctgctt ttttcaaaga tcttggtttt actgaaattg tccatatcga caatcacatc 360agtttcttgg aaaataaaaa aactggtttt caagattatc tgatgacact taataagcct 420gagcaaacac ctggtaaagt cgctgctatt gttatcaacg ctaacccctt taccttaggg 480catcaatttt tagtagagaa agctgcaaga gaaaatgatt gggttcatct gtttatggtc 540agtgaagacc gcagtctaat tcctttttcg gtgagaaaga ggttgattca agaaggtcta 600gctcatcttg ataatgtcat atatcatgaa acaggtcctt atttgattag ccaagcgact 660ttcccagcct atttccaaaa agaagacaat gacgtgatta agagccaagc tttgctggat 720actgctattt ttctaaagat tgctcaaacc ttacagatta caaaaagata cgttggagaa 780
gagccaacca gccgagtaac tgctatttac aatgaaatta tggcagagca gttgcagcaa 840gctggtatcc tcctagatat tttgccaagg aaagctatca atcagcagca agatcctatc 900agtgcctcaa cggctaggca ggcattgaaa gataatgatt gggaccttct ggcaaaactc 960cttcccaaaa cgtctttaga ttatttttgt tcgctaaaag cccaacccat tattaaaaag 1020atacaagcca cttcatctgt caaacattac taa 1053<210>24<211>350<212>PRT<213>酿脓链球菌<400>24Met Pro Tyr Tyr Thr Ile Ser Lys Val Phe Pro Ser Asp Lys Thr Thr1 5 10 15Met Ala Ser Val Lys Asn Leu Leu His Gln Glu Gly Ile Arg Leu Asp20 25 30Ala His Leu Asp Tyr Thr Cys Ala Ile Met Asn Ala Gln Asn Asp Val35 40 45Ile Ala Thr Gly Ser Tyr Phe Gly Asn Ser Leu Arg Cys Leu Cys Val50 55 60Ser Ser Ala Tyr Gln Gly Glu Gly Leu Leu Asn Arg Ile Val Ser His65 70 75 80Leu Ile Asp Glu Glu Tyr Ala Leu Gly Asn Tyr His Leu Phe Val Tyr85 90 95Thr Lys Thr Ser Ser Ala Ala Phe Phe Lys Asp Leu Gly Phe Thr Glu100 105 110Ile Val His Ile Asp Asn His Ile Ser Phe Leu Glu Asn Lys Lys Thr115 120 125Gly Phe Gln Asp Tyr Leu Met Thr Leu Asn Lys Pro Glu Gln Thr Pro130 135 140Gly Lys Val Ala Ala Ile Val Ile Asn Ala Asn Pro Phe Thr Leu Gly145 150 155 160His Gln Phe Leu Val Glu Lys Ala Ala Arg Glu Asn Asp Trp Val His165 170 175Leu Phe Met Val Ser Glu Asp Arg Ser Leu Ile Pro Phe Ser Val Arg180 185 190
Lys Arg Leu Ile Gln Glu Gly Leu Ala His Leu Asp Asn Val Ile Tyr195 200 205His Glu Thr Gly Pro Tyr Leu Ile Ser Gln Ala Thr Phe Pro Ala Tyr210 215 220Phe Gln Lys Glu Asp Asn Asp Val Ile Lys Ser Gln Ala Leu Leu Asp225 230 235 240Thr Ala Ile Phe Leu Lys Ile Ala Gln Thr Leu Gln Ile Thr Lys Arg245 250 255Tyr Val Gly Glu Glu Pro Thr Ser Arg Val Thr Ala Ile Tyr Asn Glu260 265 270Ile Met Ala Glu Gln Leu Gln Gln Ala Gly Ile Leu Leu Asp Ile Leu275 280 285Pro Arg Lys Ala Ile Asn Gln Gln Gln Asp Pro Ile Ser Ala Ser Thr290 295 300Ala Arg Gln Ala Leu Lys Asp Asn Asp Trp Asp Leu Leu Ala Lys Leu305 310 315 320Leu Pro Lys Thr Ser Leu Asp Tyr Phe Cys Ser Leu Lys Ala Gln Pro325 330 335Ile Ile Lys Lys Ile Gln Ala Thr Ser Ser Val Lys His Tyr340 345 350<210>25<21l>642<212>DNA<213>酿脓链球菌<400>25atggtgataa ggttgttgct cttattgaat accgtgacgg tagcctcatg gatgtggttt 60acaatgtgta aagacactta tttttcaggc gaagctatcc aacttagtga tatgttaaga 120gcccgcgaag aaagagctct gcgtcagctg catttattaa aggagtaccc agaaggtagc 180ttattatcgg tcaccatgaa tatccctgga ccaattaaaa cctctcctaa acttcttgaa 240gcttttgata tagtgattaa ggccattcaa actgccttag ctgacgataa gatttgttac 300cagttgcgat tactgcctac aacgggttat gagtattacc tcatcacaag tctacctagc 360cgcgacctga agttaaaaat gatagcctta gagacagagt tgccaatagg tcgtctcatg 420gatttagatg tcttggtctt gcaaaatgat ctgcctcatt caattagcag aaccgtatta 480ggaggctccc ctaggcaatg ttttatctgt tctaaagagg ccaaagtctg cggtcgccta 540cgtaagcaca gtgtcgagga gatgcagact gctatttcaa aattactcca ttcatttttc 600aataaagaca accaatcatc gtcatcagat aagacaggtt ga642
<210>26<211>213<212>PRT<213>酿脓链球菌<400>26Met Val Ile Arg Leu Leu Leu Leu Leu Asn Thr Val Thr Val Ala Ser1 5 10 15Trp Met Trp Phe Thr Met Cys Lys Asp Thr Tyr Phe Ser Gly Glu Ala20 25 30Ile Gln Leu Ser Asp Met Leu Arg Ala Arg Glu Glu Arg Ala Leu Arg35 40 45Gln Leu His Leu Leu Lys Glu Tyr Pro Glu Gly Ser Leu Leu Ser Val50 55 60Thr Met Asn Ile Pro Gly Pro Ile Lys Thr Ser Pro Lys Leu Leu Glu65 70 75 80Ala Phe Asp Ile Val Ile Lys Ala Ile Gln Thr Ala Leu Ala Asp Asp85 90 95Lys Ile Cys Tyr Gln Leu Arg Leu Leu Pro Thr Thr Gly Tyr Glu Tyr100 105 110Tyr Leu Ile Thr Ser Leu Pro Ser Arg Asp Leu Lys Leu Lys Met Ile115 120 125Ala Leu Glu Thr Glu Leu Pro Ile Gly Arg Leu Met Asp Leu Asp Val130 135 140Leu Val Leu Gln Asn Asp Leu Pro His Ser Ile Ser Arg Thr Val Leu145 150 155 160Gly Gly Ser Pro Arg Gln Cys Phe Ile Cys Ser Lys Glu Ala Lys Val165 170 175Cys Gly Arg Leu Arg Lys His Ser Val Glu Glu Met Gln Thr Ala Ile180 185 190Ser Lys Leu Leu His Ser Phe Phe Asn Lys Asp Asn Gln Ser Ser Ser195 200 205Ser Asp Lys Thr Gly210
<210>27<211>1395<212>DNA<213>酿脓链球菌<400>27atgacgaaaa tccgtataac ggaaacagtt ttacgtgatg gtcaacaaag tcagattgcc 60acacgtatga caaccaagga aatgattcct attctcgaaa cgctagacaa tgctggttat 120catgcccttg aaatgtgggg aggagcaacc tttgattcct gcctacgctt tttaaatgaa 180gacccttggg aacggctaag agccatccgt aaagcagtga aaaagactaa acttcagatg 240ctcttacgcg gacaaaacct tcttggatat cgcaattatg ctgacgatgt ggtcagatcc 300tttattcaaa aatccattga aaatgggatt gatattgtcc gtattttcga tgctttaaac 360gacccacgca acttgcaaac agctgtttca gcgactaaaa aatttggagg gcatgctcaa 420gttgccattt cttacacgac aagtccggta cataccattg actactttgt tgaattggcg 480aaagcttacc aagctatcgg agcggactcc atttgtatca aagacatggc tggtgtctta 540actcctgaaa taggttacca attggtcaaa tgtatcaagg agaatacaac tatccctctt 600gaggttcata cccatgctac cagtggtatt tcagaaatga cttacttaaa agtagcagaa 660gcaggagctg atattattga tacggcgatt tcctcttttt cagggggaac cagtcagcct 720gccacagagt caatggcgat tgccttgacg gatttaggct ttgacacagg cttggatatg 780caagaggtgg ccaaagttgc agaatatttc aacactattc gtgaccacta tcgagaaata 840gggattttaa atcctaaagt caaagatact gagccaaaaa cattgattta ccaagttcca 900ggtggcatgc tatcaaacct attgagccaa ttaaccgagc aaggcctaac tgataaatac 960gaagaagtct tagcagaagt acctaaagta agggctgatc ttgggtatcc gccactcgta 1020acgccattat cacaaatggt tggcacacag gccttgatga atatcatctc aggggaacgt 1080tacaaggtag ttccaaatga aatcaaagac tatgttcgag ggctatacgg tcaatcacca 1140gcgccattag cagaaggtat caaagagaaa atcattggtg acgaagcagt tattacttgc 1200agaccagccg acctaatcga gcctcaaatg atttatctac gtgacgagat tgctccatac 1260gctcattcag aagaagacgt gttaagctat gcaagcttcc cgcaacaagc tagagatttc 1320ttgggacgcc gtgaagatcc tttctatgat gttccggttc aagaagttac tgtacaactg 1380gacattcaag actaa 1395<210>28<211>464<212>PRT<213>酿脓链球菌<400>28Met Thr Lys Ile Arg Ile Thr Glu Thr Val Leu Arg Asp Gly Gln Gln1 5 10 15Ser Gln Ile Ala Thr Arg Met Thr Thr Lys Glu Met Ile Pro Ile Leu20 25 30Glu Thr Leu Asp Asn Ala Gly Tyr His Ala Leu Glu Met Trp Gly Gly35 40 45
Ala Thr Phe Asp Ser Cys Leu Arg Phe Leu Asn Glu Asp Pro Trp Glu50 55 60Arg Leu Arg Ala Ile Arg Lys Ala Val Lys Lys Thr Lys Leu Gln Met65 70 75 80Leu Leu Arg Gly Gln Asn Leu Leu Gly Tyr Arg Asn Tyr Ala Asp Asp85 90 95Val Val Arg Ser Phe Ile Gln Lys Ser Ile Glu Asn Gly Ile Asp Ile100 105 110Val Arg Ile Phe Asp Ala Leu Asn Asp Pro Arg Asn Leu Gln Thr Ala115 120 125Val Ser Ala Thr Lys Lys Phe Gly Gly His Ala Gln Val Ala Ile Ser130 135 140Tyr Thr Thr Ser Pro Val His Thr Ile Asp Tyr Phe Val Glu Leu Ala145 150 155 160Lys Ala Tyr Gln Ala Ile Gly Ala Asp Ser Ile Cys Ile Lys Asp Met165 170 175Ala Gly Val Leu Thr Pro Glu Ile Gly Tyr Gln Leu Val Lys Cys Ile180 185 190Lys Glu Asn Thr Thr Ile Pro Leu Glu Val His Thr His Ala Thr Ser195 200 205Gly Ile Ser Glu Met Thr Tyr Leu Lys ValAla Glu Ala Gly Ala Asp210 215 220Ile Ile Asp Thr Ala Ile Ser Ser Phe Ser Gly Gly Thr Ser Gln Pro225 230 235 240Ala Thr Glu Ser Met Ala Ile Ala Leu Thr Asp Leu Gly Phe Asp Thr245 250 255Gly Leu Asp Met Gln Glu Val Ala Lys Val Ala Glu Tyr Phe Asn Thr260 265 270Ile Arg Asp His Tyr Arg Glu Ile Gly Ile Leu Asn Pro Lys Val Lys275 280 285Asp Thr Glu Pro Lys Thr Leu Ile Tyr Gln Val Pro Gly Gly Met Leu290 295 300
Ser Asn Leu Leu Ser Gln Leu Thr Glu Gln Gly Leu Thr Asp Lys Tyr305 310 315 320Glu Glu Val Leu Ala Glu Val Pro Lys Val Arg Ala Asp Leu Gly Tyr325 330 335Pro Pro Leu Val Thr Pro Leu Ser Gln Met Val Gly Thr Gln Ala Leu340 345 350Met Asn Ile Ile Ser Gly Glu Arg Tyr Lys Val Val Pro Asn Glu Ile355 360 365Lys Asp Tyr Val Arg Gly Leu Tyr Gly Gln Ser Pro Ala Pro Leu Ala370 375 380Glu GIy Ile Lys Glu Lys Ile Ile Gly Asp Glu Ala Val Ile Thr Cys385 390 395 400Arg Pro Ala Asp Leu Ile Glu Pro Gln Met Ile Tyr Leu Arg Asp Glu405 410 415Ile Ala Pro Tyr Ala His Ser Glu Glu Asp Val Leu Ser Tyr Ala Ser420 425 430Phe Pro Gln Gln Ala Arg Asp Phe Leu Gly Arg Arg Glu Asp Pro Phe435 440 445Tyr Asp Val Pro Val Gln Glu Val Thr Val Gln Leu Asp Ile Gln Asp450 455 460<210>29<211>1224<212>DNA<213>酿脓链球菌<400>29atgacgaatt taacgtttta tgcaaaaatc ggtatttcag aagaagagca tgactctttt 60gttaaagaac atcagcaaat tagcgtttta caaggtagtg attgggcaaa aatcaaaaat 120caatggcaga atgagcgaat tggtatctat aaagaggaaa agcaggttgc ctctttatca 180cttttgatta agctattgcc acttggaaga agcattattt atattccaag agggccagtc 240atggattatc ttgaccgtga tttggtggca tttaccatga aaacactaaa ggattatggt 300aaaactaaaa aggccctctt tatcaaatat gatccagcta tcctgttaaa acaatacgca 360ctgggacagg aagaagaaga aaaaccttta gctttagcag ctattaagaa tctccaagaa 420gctggtgttc attggactgg tttaacaatg gagattgcag atagtatcca acctcgtttc 480
caagctaata tttacactca agaaaacctt gagatgcaat ttcctaagca taccagacgt 540ttaataaaag atgctaagca gcgtggtgta aaaacatatc gtgtcagtca atcagaactt 600cacaaatttt ccaagattgt ctccttaaca gaaaaacgta aaaatatttc tttgcgtaac 660gaagcttact ttcaaaagtt gatgactact tatggggata aggcctactt acatctagca 720aaagtgaata ttcctcaaaa actagatcaa taccgccagc aattaattct tattaaccaa 780gatattactc gcacccaagc tcatcaaaag aagcgtttaa aaaaattaga agatcaaaaa 840gcttctttag aacgttatat aactgaattt gaaggcttta cagaccaata tcctgaggaa 900gttgttgtag caggtatatt atctatttct tatggaaatg ttatggaaat gctttatgct 960gggatgaatg atgattttaa gaagttttat cctcagtatc tgctgtatcc taatgttttt 1020caggatgctt atcaagatgg tattatttgg gctaacatgg gaggagtaga aggctcgctt 1080gatgatggac ttaccaaatt taaggccaac tttgctccga caatagaaga atttatagga 1140gaatttaatc tccctgtcag cccactttat catattgcta ataccatgta caaaatacga 1200aaacagttaa agaataaaca ttaa1224<210>30<211>407<212>PRT<213>酿脓链球菌<400>30Met Thr Asn Leu Thr Phe Tyr Ala Lys Ile Gly Ile Ser Glu Glu Glu1 5 10 15His Asp Ser Phe Val Lys Glu His Gln Gln Ile Ser Val Leu Gln Gly20 25 30Ser Asp Trp Ala Lys Ile Lys Asn Gln Trp Gln Asn Glu Arg Ile Gly35 40 45Ile Tyr Lys Glu Glu Lys Gln Val Ala Ser Leu Ser Leu Leu Ile Lys50 55 60Leu Leu Pro Leu Gly Arg Ser Ile Ile Tyr Ile Pro Arg Gly Pro Val65 70 75 80Met Asp Tyr Leu Asp Arg Asp Leu Val Ala Phe Thr Met Lys Thr Leu85 90 95Lys Asp Tyr Gly Lys Thr Lys Lys Ala Leu Phe Ile Lys Tyr Asp Pro100 105 110Ala Ile Leu Leu Lys Gln Tyr Ala Leu Gly Gln Glu Glu Glu Glu Lys115 120 125Pro Leu Ala Leu Ala Ala Ile Lys Asn Leu Gln Glu Ala Gly Val His130 135 140Trp Thr Gly Leu Thr Met Glu Ile Ala Asp Ser Ile Gln Pro Arg Phe
145 150 155 160Gln Ala Asn Ile Tyr Thr Gln Glu Asn Leu Glu Met Gln Phe Pro Lys165 170 175His Thr Arg Arg Leu Ile Lys Asp Ala Lys Gln Arg Gly Val Lys Thr180 185 190Tyr Arg Val Ser Gln Ser Glu Leu His Lys Phe Ser Lys Ile Val Ser195 200 205Leu Thr Glu Lys Arg Lys Asn Ile Ser Leu Arg Asn Glu Ala Tyr Phe210 215 220Gln Lys Leu Met Thr Thr Tyr Gly Asp Lys Ala Tyr Leu His Leu Ala225 230 235 240Lys Val Asn Ile Pro Gln Lys Leu Asp Gln Tyr Arg Gln Gln Leu Ile245 250 255Leu Ile Asn Gln Asp Ile Thr Arg Thr Gln Ala His Gln Lys Lys Arg260 265 270Leu Lys Lys Leu Glu Asp Gln Lys Ala Ser Leu Glu Arg Tyr Ile Thr275 280 285Glu Phe Glu Gly Phe Thr Asp Gln Tyr Pro Glu Glu Val Val Val Ala290 295 300Gly Ile Leu Ser Ile Ser Tyr Gly Asn Val Met Glu Met Leu Tyr Ala305 310 315 320Gly Met Asn Asp Asp Phe Lys Lys Phe Tyr Pro Gln Tyr Leu Leu Tyr325 330 335Pro Asn Val Phe Gln Asp Ala Tyr Gln Asp Gly Ile Ile Trp Ala Asn340 345 350Met Gly Gly Val Glu Gly Ser Leu Asp Asp Gly Leu Thr Lys Phe Lys355 360 365Ala Asn Phe Ala Pro Thr Ile Glu Glu Phe Ile Gly Glu Phe Asn Leu370 375 380Pro Val Ser Pro Leu Tyr His Ile Ala Asn Thr Met Tyr Lys Ile Arg385 390 395 400Lys Gln Leu Lys Asn Lys His405
<210>31<211>483<212>DNA<213>酿脓链球菌<400>31atgccaaaga gaataagaaa agctctagga gtagttggga aactgatgtc aattgttcct 60gacactactg aaattattgg aaaaacgatt gataacagtc gaccaattat cgaaaaacgt 120atggaacaaa aacatgaaaa agagatgcaa ttacgcacga taaatgatgt gattaatctt 180cctgttgatc aggcacaagc tcatttggaa caacttggct ttgtagtagc cactatacct 240gctaagcctc ataaaaaatg gcttcatagt aatctcaatg aagtggttgc tatgtctcca 300aaatctggta aatataagat aggaagcctg atcaaactct actacattac tgttgatgtt 360ttggaaaaaa gtcaagactt attagaccaa gaaaacttgc ggactgtgga acgcaatcaa 420aaaatcgctg atacttttga gtctgtcaaa cacattcgat ttccttttaa aaaatggcgt 480taa 483<210>32<211>160<212>PRT<213>酿脓链球菌<400>32Met Pro Lys Arg Ile Arg Lys Ala Leu Gly Val Val Gly Lys Leu Met1 5 10 15Ser Ile Val Pro Asp Thr Thr Glu Ile Ile Gly Lys Thr Ile Asp Asn20 25 30Ser Arg Pro Ile Ile Glu Lys Arg Met Glu Gln Lys His Glu Lys Glu35 40 45Met Gln Leu Arg Thr Ile Asn Asp Val Ile Asn Leu Pro Val Asp Gln50 55 60Ala Gln Ala His Leu Glu Gln Leu Gly Phe Val Val Ala Thr Ile Pro65 70 75 80Ala Lys Pro His Lys Lys Trp Leu His Ser Asn Leu Asn Glu Val Val85 90 95Ala Met Ser Pro Lys Ser Gly Lys Tyr Lys Ile Gly Ser Leu Ile Lys100 105 110Leu Tyr Tyr Ile Thr Val Asp Val Leu Glu Lys Ser Gln Asp Leu Leu115 120 125
Asp Gln Glu Asn Leu Arg Thr Val Glu Arg Asn Gln Lys Ile Ala Asp130 135 140Thr Phe Glu Ser Val Lys His Ile Arg Phe Pro Phe Lys Lys Trp Arg145 150 155 160<210>33<211>1345<212>DNA<213>酿脓链球菌<400>33atgatgttaa cgaaggggca acttccctat agtgctgctt ttacaacagg agggctcttt 60tactttgtta tcattgcatt aagttattat ttgggatcga cactttggct agtctttgtt 120caggtgtttt gtttttactt atctggttta tatctttata aactcattaa ttatatgaca 180ggctttcaaa aagtggcttt aactttttca attagctact atttattatc tgttagtctt 240ggttttgggg gattgtatcc tactcaactg gctatgccat ttatattaat atcggcttgg 300tttttaacta agtattttgc ctgtttagtg aaagatgagg catttattct ttttggcttt 360gtaggtgctc ttgcaatgct aattgacccg agtaccctta tcttttggtc ttttgcttgt 420gtgacagttt tttcttataa tataagccaa aagcatcttg caagaggttt ttatcaactg 480ctagcttcga tttttggaat gattttagtt ttttacacag caggatattt cattttgaac 540ttacaagtgc taaatcctta tttatcacaa acgatgattt atccttttac tttttttaaa 600tcaggaaact tatcgttgct ttttggactg gctattcagt tgttcttcgc tttggggctt 660ggtcttttga cgggaatgga gaatgtcatt aggcgattta aaaacaattc tgatagggtc 720gtcaagtggc tatttgtcat ggtcattcta gaatctatac ttgtggctat attttcacaa 780gactatcgcc cctatcatct tttacctctt ttaccttttg gattaatttt gactgctatt 840cctgttggct atcagtatgg tataggatta ggtcagagta gtcatcgcag acgtcatggt 900aaaaatggtg ttggtcgagt aatgatgatt tatcttaaga gacactttta tttgccaatt 960ttaattgtag ggacaatact aatctgttct acttattgtt tcattagtag tattcctctt 1020aatcaggagc gtgatcatat tgctagttat ttagaacaga aactaaataa aactcaatct 1080atttatgttt gggatgatac ttctaaaatt tatttggaca gtaaagctaa atctgtttct 1140caatttagtt ctcctgacat caatacgcaa aaagagagtc atcgaaaaat attagaagat 1200gaactattag aaaataaggc tgcttatatc gttgttaatc gctataaaaa cctgcctaaa 1260atcattcaaa aagtattatc tactaattac aaagtagata aacagataac gacaaaaagt 1320tttattgttt atcagaaaaa gtaat 1345<210>34<211>447<212>PRT<213>酿脓链球菌<400>34
Met Met Leu Thr Lys Gly Gln Leu Pro Tyr Ser Ala Ala Phe Thr Thr1 5 10 15Gly Gly Leu Phe Tyr Phe Val Ile Ile Ala Leu Ser Tyr Tyr Leu Gly20 25 30Ser Thr Leu Trp Leu Val Phe Val Gln Val Phe Cys Phe Tyr Leu Ser35 40 45Gly Leu Tyr Leu Tyr Lys Leu Ile Asn Tyr Met Thr Gly Phe Gln Lys50 55 60Val Ala Leu Thr Phe Ser Ile Ser Tyr Tyr Leu Leu Ser Val Ser Leu65 70 75 80Gly Phe Gly Gly Leu Tyr Pro Thr Gln Leu Ala Met Pro Phe Ile Leu85 90 95Ile Ser Ala Trp Phe Leu Thr Lys Tyr Phe Ala Cys Leu Val Lys Asp100 105 110Glu Ala Phe Ile Leu Phe Gly Phe Val Gly Ala Leu Ala Met Leu Ile115 120 125Asp Pro Ser Thr Leu Ile Phe Trp Ser Phe Ala Cys Val Thr Val Phe130 135 140Ser Tyr Asn Ile Ser Gln Lys His Leu Ala Arg Gly Phe Tyr Gln Leu145 150 155 160Leu Ala Ser Ile Phe Gly Met Ile Leu Val Phe Tyr Thr Ala Gly Tyr165 170 175Phe Ile Leu Asn Leu Gln Val Leu Asn Pro Tyr Leu Ser Gln Thr Met180 185 190Ile Tyr Pro Phe Thr Phe Phe Lys Ser Gly Asn Leu Ser Leu Leu Phe195 200 205Gly Leu Ala Ile Gln Leu Phe Phe Ala Leu Gly Leu Gly Leu Leu Thr210 215 220Gly Met Glu Asn Val Ile Arg Arg Phe Lys Asn Asn Ser Asp Arg Val225 230 235 240Val Lys Trp Leu Phe Val Met Val Ile Leu Glu Ser Ile Leu Val Ala245 250 255Ile Phe Ser Gln Asp Tyr Arg Pro Tyr His Leu Leu Pro Leu Leu Pro
260 265 270Phe Gly Leu Ile Leu Thr Ala Ile Pro Val Gly Tyr Gln Tyr Gly Ile275 280 285Gly Leu Gly Gln Ser Ser His Arg Arg Arg His Gly Lys Asn Gly Val290 295 300Gly Arg Val Met Met Ile Tyr Leu Lys Arg His Phe Tyr Leu Pro Ile305 310 315 320Leu Ile Val Gly Thr Ile Leu Ile Cys Ser Thr Tyr Cys Phe Ile Ser325 330 335Ser Ile Pro Leu Asn Gln Glu Arg Asp His Ile Ala Ser Tyr Leu Glu340 345 350Gln Lys Leu Asn Lys Thr Gln Ser Ile Tyr Val Trp Asp Asp Thr Ser355 360 365Lys Ile Tyr Leu Asp Ser Lys Ala Lys Ser Val Ser Gln Phe Ser Ser370 375 380Pro Asp Ile Asn Thr Gln Lys Glu Ser His Arg Lys Ile Leu Glu Asp385 390 395 400Glu Leu Leu Glu Asn Lys Ala Ala Tyr Ile Val Val Asn Arg Tyr Lys405 410 415Asn Leu Pro Lys Ile Ile Gln Lys Val Leu Ser Thr Asn Tyr Lys Val420 425 430Asp Lys Gln Ile Thr Thr Lys Ser Phe Ile Val Tyr Gln Lys Lys435 440 445<210>35<211>618<212>DNA<213>酿脓链球菌<400>35atgattaaag ctcagctaaa gaatctaata aaaacaattc atctcgtaaa agaggctggt 60ttctccctaa atggttcatt gtacatggag ttattgcatg attttacgca tgatgagtta 120gtacataacc ctataatcga aagtacggtt gatacaattc agtcagttga atttgaaagg 180gtttcttttt catataatgg taaggataat gtaataaacg atataagttt ttcaattaaa 240gcaggagaga ggttagcaat tgttggtgga aatggttctg gaaaaagtac gattttcaaa 300ttagcctgcg gtctttacga taattatgaa ggcaatatat atataaatgg tattaatctt 360
tgttcaatac agaaaaagtc atactacaag agaatatccg cattgttcca agatttttta 420aagtatgaat tgacactgcg tgaaaatgtt ggattgggtg aattatcaaa gttatatagt 480gatgagtctt ataatacttc attttttacc acatcatggg attcagagaa tgaactgcga 540ttggaggata tttatataag atatagtgat ggtaagtttc attttacaac tatcgatgaa 600tcgattaaac gggattaa 618<210>36<211>205<212>PRT<213>酿脓链球菌<400>36Met Ile Lys Ala Gln Leu Lys Asn Leu Ile Lys Thr Ile His Leu Val1 5 10 15Lys Glu Ala Gly Phe Ser Leu Asn Gly Ser Leu Tyr Met Glu Leu Leu20 25 30His Asp Phe Thr His Asp Glu Leu Val His Asn Pro Ile Ile Glu Ser35 40 45Thr Val Asp Thr Ile Gln Ser Val Glu Phe Glu Arg Val Ser Phe Ser50 55 60Tyr Asn Gly Lys Asp Asn Val Ile Asn Asp Ile Ser Phe Ser Ile Lys65 70 75 80Ala Gly Glu Arg Leu Ala Ile Val Gly Gly Asn Gly Ser Gly Lys Ser85 90 95Thr Ile Phe Lys Leu Ala Cys Gly Leu Tyr Asp Asn Tyr Glu Gly Asn100 105 110Ile Tyr Ile Asn Gly Ile Asn Leu Cys Ser Ile Gln Lys Lys Ser Tyr115 120 125Tyr Lys Arg Ile Ser Ala Leu Phe Gln Asp Phe Leu Lys Tyr Glu Leu130 135 140Thr Leu Arg Glu Asn Val Gly Leu Gly Glu Leu Ser Lys Leu Tyr Ser145 150 155 160Asp Glu Ser Tyr Asn Thr Ser Phe Phe Thr Thr Ser Trp Asp Ser Glu165 170 175Asn Glu Leu Arg Leu Glu Asp Ile Tyr Ile Arg Tyr Ser Asp Gly Lys180 185 190
Phe His Phe Thr Thr Ile Asp Glu Ser Ile Lys Arg Asp195 200 205<210>37<211>1434<212>DNA<213>酿脓链球菌<400>37atgctaagaa aaaagagaat tttgggttta tttcgacttg ttgaattaat tttcctagga 60ttattgttga gtttagttgt ttcgtacctt gcgtggacca atagttttgc aacacttcat 120aatatattag caactgtcgg aatagtggaa cgaagcaaag atcaacagcc tcgctatcac 180attggacaag ctattcaagt acaaaaaagt ggtccatatc atcaatggat tggaactatt 240aataaacagg tagaagatat agccgaaaat taccgagtga gttatcatta tgaagtggta 300tttccaatag gaaaagtcac tgtttctttg ccagaacata acctgaaaga gcctgataaa 360ccgaggttta aaaaaggaga tatcgttaaa ttatcttcat taactaaaaa gccacatata 420aaagtatatc aaggtcaatt agcgactatt aaacaagtta aaaaatgcta tgactattcg 480ttaggaggat atcagtacga tattaatctg aaagataatc taagattaga tggaatttca 540gagcaagatt ttgttaaacc ttattatatt aggttcaata aaggaaattc ccctgagcaa 600aacaatcgtc ttttgcgaaa agctttcgct tatgcaaagc agcatccaaa tagcgttata 660tcttttccaa aggggcaatt tcacattggc tctttgcctt cacaaaaaga ttattttgag 720cttccatctg atacagctat tattggtcat cagacagagt tcattattca cggtaaaatg 780ttgtggtttg gattccctac aggaccaaag gctgaacaag gtgttcgtaa tctcgtgttg 840actggagtgc atttcaaagc aaatgatttg aaaaaaggag accactttat gattatggct 900gatcatggta ctgattggca tatttacgat aacaaattta ctatggttca taagcgtaat 960agtcatattt ttgatttagg atctctacaa aattcattgt ttgagaaaaa ccaatttatt 1020ggctatgcgc cagaattagt acaagaccaa cagctgctat caaaggctca agggcatgat 1080tttttttcag aagtcattca gtttgatgct gctgttcatc attttgcatg ggatggaggt 1140ctacttagta atattgctcc aaactatgaa gcatttaacc aaactcgaca tctatgtcac 1200aatattactg taagccaaaa tcaattttta ccttatatag atccgactgg ttgcctgaga 1260gcctatagtg gttctattgg tcagcattcc tcaaaagtag gagttattag ggttttaaat 1320aatgttttta cctcatccat tgttactaaa gcgaagctca ctagttggtt tatggaacct 1380attcattttc caccaaattc accggttatt gtcgcaggta atatcattaa ttga 1434<210>38<211>477<212>PRT<213>酿脓链球菌<400>38Met Leu Arg Lys Lys Arg Ile Leu Gly Leu Phe Arg Leu Val Glu Leu1 5 10 15Ile Phe Leu Gly Leu Leu Leu Ser Leu Val Val Ser Tyr Leu Ala Trp20 25 30
Thr Asn Ser Phe Ala Thr Leu His Asn Ile Leu Ala Thr Val Gly Ile35 40 45Val Glu Arg Ser Lys Asp Gln Gln Pro Arg Tyr His Ile Gly Gln Ala50 55 60Ile Gln Val Gln Lys Ser Gly Pro Tyr His Gln Trp Ile Gly Thr Ile65 70 75 80Asn Lys Gln Val Glu Asp Ile Ala Glu Asn Tyr Arg Val Ser Tyr His85 90 95Tyr Glu Val Val Phe Pro Ile Gly Lys Val Thr Val Ser Leu Pro Glu100 105 110His Asn Leu Lys Glu Pro Asp Lys Pro Arg Phe Lys Lys Gly Asp Ile115 120 125Val Lys Leu Ser Ser Leu Thr Lys Lys Pro His Ile Lys Val Tyr Gln130 135 140Gly Gln Leu Ala Thr Ile Lys Gln Val Lys Lys Cys Tyr Asp Tyr Ser145 150 155 160Leu Gly Gly Tyr Gln Tyr Asp Ile Asn Leu Lys Asp Asn Leu Arg Leu165 170 175Asp Gly Ile Ser Glu Gln Asp Phe Val Lys Pro Tyr Tyr Ile Arg Phe180 185 190Asn Lys Gly Asn Ser Pro Glu Gln Asn Asn Arg Leu Leu Arg Lys Ala195 200 205Phe Ala Tyr Ala Lys Gln His Pro Asn Ser Val Ile Ser Phe Pro Lys210 215 220Gly Gln Phe His Ile Gly Ser Leu Pro Ser Gln Lys Asp Tyr Phe Glu225 230 235 240Leu Pro Ser Asp Thr Ala Ile Ile Gly His Gln Thr Glu Phe Ile Ile245 250 255His Gly Lys Met Leu Trp Phe Gly Phe Pro Thr Gly Pro Lys Ala Glu260 265 270Gln Gly Val Arg Asn Leu Val Leu Thr Gly Val His Phe Lys Ala Asn275 280 285Asp Leu Lys Lys Gly Asp His Phe Met Ile Met Ala Asp His Gly Thr
290 295 300Asp Trp His Ile Tyr Asp Asn Lys Phe Thr Met Val His Lys Arg Asn305 310 315 320Ser His Ile Phe Asp Leu Gly Ser Leu Gln Asn Ser Leu Phe Glu Lys325 330 335Asn Gln Phe Ile Gly Tyr Ala Pro Glu Leu Val Gln Asp Gln Gln Leu340 345 350Leu Ser Lys Ala Gln Gly His Asp Phe Phe Ser Glu Val Ile Gln Phe355 360 365Asp Ala Ala Val His His Phe Ala Trp Asp Gly Gly Leu Leu Ser Asn370 375 380Ile Ala Pro Asn Tyr Glu Ala Phe Asn Gln Thr Arg His Leu Cys His385 390 395 400Asn Ile Thr Val Ser Gln Asn Gln Phe Leu Pro Tyr Ile Asp Pro Thr405 410 415Gly Cys Leu Arg Ala Tyr Ser Gly Ser Ile Gly Gln His Ser Ser Lys420 425 430Val Gly Val Ile Arg Val Leu Asn Asn Val Phe Thr Ser Ser Ile Val435 440 445Thr Lys Ala Lys Leu Thr Ser Trp Phe Met Glu Pro Ile His Phe Pro450 455 460Pro Asn Ser Pro Val Ile Val Ala Gly Asn Ile Ile Asn465 470 475<210>39<211>1020<212>DNA<213>酿脓链球菌<400>39atgtcaactc acttaagaaa acttccaggg ctgttacttt gcttattgtt agctcttcca 60gcctggtgtt tagggcgctt atttcccatt attggagcac ctgtttttgc tattctttta 120ggaatgttgt tagccttgtt ttatgaacat cgtgacaaga ctaaagaggg aattagtttt 180acatccaagt atattttaca aacagcagtg gttttgcttg gttttggatt aaacctaacc 240caagttatgg cagtgggcat gcagtcttta ccgattatca tttcaactat tgcgacagct 300cttttggtag cttatggctt acagaaatgg ctgcgcttag atgtcaatac agccaccttg 360
gtaggtgtag gatcttccat ttgtgggggg tctgctgttg cagcgacagc tcctgtcatt 420aaggcaaagg atgacgaggt tgctaaggca atttcagtca tttttctctt taatatgtta 480gcagctttgc tatttccaag tttaggacaa ttactaggct tatctaatga aggttttgct 540atttttgccg ggacagctgt taacgacact tcttccgtga ctgcaacggc cacggcctgg 600gatgcccttc accattccaa tacactagat ggagcaacca ttgttaaatt gactcgcacc 660ttggctattc tcccaattac tttaggttta tccctttacc gagcgaaaaa agagcacgac 720atcgttacag aagaaaactt tagccttagg aagtcattcc ctcgtttcat cctcttcttt 780ttattagctt ctctcatcac aacattgatg accagtttgg gagtttctgc cgatagtttc 840cattacctaa aaaccttatc aaaattcttt atcgtgatgg ctatggcagc gattggttta 900aacacaaacc tggttaaact gattaagacg ggcggtcagg ctatcctttt aggagctatt 960tgctgggtag ctatcaccct tgtcagttta gccatgcaat taagtttggg catttggtaa 1020<210>40<211>339<212>PRT<213>酿脓链球菌<400>40Met Ser Thr His Leu Arg Lys Leu Pro Gly Leu Leu Leu Cys Leu Leu1 5 10 15Leu Ala Leu Pro Ala Trp Cys Leu Gly Arg Leu Phe Pro Ile Ile Gly20 25 30Ala Pro Val Phe Ala Ile Leu Leu Gly Met Leu Leu Ala Leu Phe Tyr35 40 45Glu His Arg Asp Lys Thr Lys Glu Gly Ile Ser Phe Thr Ser Lys Tyr50 55 60Ile Leu Gln Thr Ala Val Val Leu Leu Gly Phe Gly Leu Asn Leu Thr65 70 75 80Gln Val Met Ala Val Gly Met Gln Ser Leu Pro Ile Ile Ile Ser Thr85 90 95Ile Ala Thr Ala Leu Leu Val Ala Tyr Gly Leu Gln Lys Trp Leu Arg100 105 110Leu Asp Val Asn Thr Ala Thr Leu Val Gly Val Gly Ser Ser Ile Cys115 120 125Gly Gly Ser Ala Val Ala Ala Thr Ala Pro Val Ile Lys Ala Lys Asp130 135 140Asp Glu Val Ala Lys Ala Ile Ser Val Ile Phe Leu Phe Asn Met Leu145 150 155 160
Ala Ala Leu Leu Phe Pro Ser Leu Gly Gln Leu Leu Gly Leu Ser Asn165 170 175Glu Gly Phe Ala Ile Phe Ala Gly Thr Ala Val Asn Asp Thr Ser Ser180 185 190Val Thr Ala Thr Ala Thr Ala Trp Asp Ala Leu His His Ser Asn Thr195 200 205Leu Asp Gly Ala Thr Ile Val Lys Leu Thr Arg Thr Leu Ala Ile Leu210 215 220Pro Ile Thr Leu Gly Leu Ser Leu Tyr Arg Ala Lys Lys Glu His Asp225 230 235 240Ile Val Thr Glu Glu Asn Phe Ser Leu Arg Lys Ser Phe Pro Arg Phe245 250 255Ile Leu Phe Phe Leu Leu Ala Ser Leu Ile Thr Thr Leu Met Thr Ser260 265 270Leu Gly Val Ser Ala Asp Ser Phe His Tyr Leu Lys Thr Leu Ser Lys275 280 285Phe Phe Ile Val Met Ala Met Ala Ala Ile Gly Leu Asn Thr Asn Leu290 295 300Val Lys Leu Ile Lys Thr Gly Gly Gln Ala Ile Leu Leu Gly Ala Ile305 310 315 320Cys Trp Val Ala Ile Thr Leu Val Ser Leu Ala Met Gln Leu Ser Leu325 330 335Gly Ile Trp<210>41<211>2637<212>DNA<213>酿脓链球菌<400>41atgataaaga aaaccttatg gaaggatatt ttgagagcta tcaagaatag taaagggcga 60ttcatttcct tatttttcct aatggcctta ggctcctttg ctttagttgg acttaaagtc 120accggtccag atatggaacg aacagccagc cgttacctcg aaagacacca ggtgatggac 180ctaacggtac tggcttctca tcaattttcc caagccgata aacaagagtt agatacgtta 240aaaggggctc atttagaata tggtcattta cttgatgtca gtctaactag caaccagaaa 300
tctcttaggc tctatagcgt gccaaagaaa gtgtctaagc cagtcttggt taaagggagt 360tggccaaagc gagagacaga tttggtttta tcctcctcac ttgctaaaaa ctatcagatt 420ggagatgaac tagcagtcac ctcacctatg gaaggtttgc tgacgacaac ccattttcaa 480gtggttggtt ttgcgaattc ttcagaagtt tggtccaagt ccaatttagg aagttcctca 540accggagatg gaagtctcta cgcttatgct tttgttaatc caaacgtttt taaaagtgcc 600tttaacctgc tgcgcatccg ttttagtcat cttcgtctga caaacgcttt ttccaaagac 660tatcaaaaaa gggtaaccca aaaccaagct catttggata atctacttaa agataatggc 720cagaagcgtt atgatgacct ccaaaatcag tatgaccttg ccttaaaaaa tggcagagca 780gcacttgcaa aggaaacagt gaaactagct gcgagtgagg agaacttaac ttttttagaa 840ggctctgctt tacaagaagc taagcatcag attgaacaag gcaaacaagc attagccaag 900gaggaaaagc agttagagca ggtgcaggct acaaaagata agctagaaaa acccagttac 960ctgacttata atcgctcgac cctaccagga ggagaaggat atcatactta tgcaacttca 1020acgacctcca tttcaaatgt tggaaatatt tttcctgttg ttctttatct cgtagctgct 1080ctagtagcct ttaccaccat gacacgttat gttgatgaag aaagaacaag ctctggtcta 1140ttaaaagcca ttggttattc taacaaggat atcagtttaa agtttcttat ctatgggctt 1200ttagccagtt ttttagggac aactttaggt attattgggg gaacttacct cttatctacc 1260ttgatttcag agatcttaac aggagctttg actattggaa agactcacct ttatagttat 1320tggttttata atggcatagc ttacttgctg gctatgttat ctgctgtttt accagcctac 1380ttaattgtca aaaaggaatt attcctcaat gcagctcagt tattgctgcc caaacctcct 1440agtaaggggg caaaaatctg gttggaacac cttacttttg tctggaaagc cctgtccttt 1500actcacaagg tgaccatacg taatattttt cgctataaac aaagaatgct gatgaccatt 1560gtaggcgttg caggctcagt agccctttta tttgcaggct tagggattca gtcgtcatta 1620gccaaagtag ttgagcatca atttggtgat ttaacgactt atgatatttt ggctgtcggt 1680tcggccaaag cgacagcgac agagcaaact gacttagcta gctatcttaa acaagaacct 1740attacagggt accaaaaggt atcttatgcc agcttaaccc ttcctgtaaa gggattacct 1800gataagcaaa gtatttccat tttatcaagt tcagctactt ctcttagtcc ctattttaat 1860ctgctggata gtcaggagca aaagaaggtt cccattccaa cctctggtgt tttgatttct 1920gagaaattag cctcctatta caaggtaaaa ccaggtgatc agttggtatt gactgatcgg 1980aaaggacagt cttataaagt gacgattaaa caggttattg acatgacagt tggccattac 2040ctgataatgt ctgataccta ttttaagaat cattttaaag gattggaggc tgctcctgcc 2100tatctgatta aggtaaaaga caaagatagc aagcacataa aggagacagc cagtgacttg 2160ttaaccttaa aagcgattag agcagtttca caaaacgtca atcatattaa atctgttcag 2220ctagtagtca cctctcttaa tcaggtcatg accctccttg tcttcttgtc tattttatta 2280gcaatcgtta tcctttataa cttaacgact attaatattg ctgagcgtat tcgagaatta 2340tccactatta aagttctggg attttacgat caggaggtca ccttatatat ttatcgagaa 2400actatttcgc tatccctagt aggcattctt ttaggtatct atttaggaaa aggcctgcat 2460acttatatca tgacaatgat ttcaactggg gatattcaat ttggtgtaaa ggttgatgct 2520tatgtttatc tagtgccaat tctagtaatc cttagcttgt tagcggtatt aggtatctgg 2580gttaatcgcc atttaaaaaa ggttgatatg ttagaagctt tgaaatccat agattga2637<210>42<211>878<212>PRT<213>酿脓链球菌<400>42Met Ile Lys Lys Thr Leu Trp Lys Asp Ile Leu Arg Ala Ile Lys Asn1 5 10 15
Ser Lys Gly Arg Phe Ile Ser Leu Phe Phe Leu Met Ala Leu Gly Ser20 25 30Phe Ala Leu Val Gly Leu Lys Val Thr Gly Pro Asp Met Glu Arg Thr35 40 45Ala Ser Arg Tyr Leu Glu Arg His Gln Val Met Asp Leu Thr Val Leu50 55 60Ala Ser His Gln Phe Ser Gln Ala Asp Lys Gln Glu Leu Asp Thr Leu65 70 75 80Lys Gly Ala His Leu Glu Tyr Gly His Leu Leu Asp Val Ser Leu Thr85 90 95Ser Asn Gln Lys Ser Leu Arg Leu Tyr Ser Val Pro Lys Lys Val Ser100 105 110Lys Pro Val Leu Val Lys Gly Ser Trp Pro Lys Arg Glu Thr Asp Leu115 120 125Val Leu Ser Ser Ser Leu Ala Lys Asn Tyr Gln Ile Gly Asp Glu Leu130 135 140Ala Val Thr Ser Pro Met Glu Gly Leu Leu Thr Thr Thr His Phe Gln145 150 155 160Val Val Gly Phe Ala Asn Ser Ser Glu Val Trp Ser Lys Ser Asn Leu165 170 175Gly Ser Ser Ser Thr Gly Asp Gly Ser Leu Tyr Ala Tyr Ala Phe Val180 185 190Asn Pro Asn Val Phe Lys Ser Ala Phe Asn Leu Leu Arg Ile Arg Phe195 200 205Ser His Leu Arg Leu Thr Asn Ala Phe Ser Lys Asp Tyr Gln Lys Arg210 215 220Val Thr Gln Asn Gln Ala His Leu Asp Asn Leu Leu Lys Asp Asn Gly225 230 235 240Gln Lys Arg Tyr Asp Asp Leu Gln Asn Gln Tyr Asp Leu Ala Leu Lys245 250 255Asn Gly Arg Ala Ala Leu Ala Lys Glu Thr Val Lys Leu Ala Ala Ser260 265 270
Glu Glu Asn Leu Thr Phe Leu Glu Gly Ser Ala Leu Gln Glu Ala Lys275 280 285His Gln Ile Glu Gln Gly Lys Gln Ala Leu Ala Lys Glu Glu Lys Gln290 295 300Leu Glu Gln Val Gln Ala Thr Lys Asp Lys Leu Glu Lys Pro Ser Tyr305 310 315 320Leu Thr Tyr Asn Arg Ser Thr Leu Pro Gly Gly Glu Gly Tyr His Thr325 330 335Tyr Ala Thr Ser Thr Thr Ser Ile Ser Asn Val Gly Asn Ile Phe Pro340 345 350Val Val Leu Tyr Leu Val Ala Ala Leu ValAla Phe Thr Thr Met Thr355 360 365Arg Tyr Val Asp Glu Glu Arg Thr Ser Ser Gly Leu Leu Lys Ala Ile370 375 380Gly Tyr Ser Asn Lys Asp Ile Ser Leu Lys Phe Leu Ile Tyr Gly Leu385 390 395 400Leu Ala Ser Phe Leu Gly Thr Thr Leu Gly Ile Ile Gly Gly Thr Tyr405 410 415Leu Leu Ser Thr Leu Ile Ser Glu Ile Leu Thr Gly Ala Leu Thr Ile420 425 430Gly Lys Thr His Leu Tyr Ser Tyr Trp Phe Tyr Asn Gly Ile Ala Tyr435 440 445Leu Leu Ala Met Leu Ser Ala Val Leu Pro Ala Tyr Leu Ile Val Lys450 455 460Lys Glu Leu Phe Leu Asn Ala Ala Gln Leu Leu Leu Pro Lys Pro Pro465 470 475 480Ser Lys Gly Ala Lys Ile Trp Leu Glu His Leu Thr Phe Val Trp Lys485 490 495Ala Leu Ser Phe Thr His Lys Val Thr Ile Arg Asn Ile Phe Arg Tyr500 505 510Lys Gln Arg Met Leu Met Thr Ile Val Gly Val Ala Gly Ser Val Ala515 520 525Leu Leu Phe Ala Gly Leu Gly Ile Gln Ser Ser Leu Ala Lys Val Val
530 535 540Glu His Gln Phe Gly Asp Leu Thr Thr Tyr Asp Ile Leu Ala Val Gly545 550 555 560Ser Ala Lys Ala Thr Ala Thr Glu Gln Thr Asp Leu Ala Ser Tyr Leu565 570 575Lys Gln Glu Pro Ile Thr Gly Tyr Gln Lys Val Ser Tyr Ala Ser Leu580 585 590Thr Leu Pro Val Lys Gly Leu Pro Asp Lys Gln Ser Ile Ser Ile Leu595 600 605Ser Ser Ser Ala Thr Ser Leu Ser Pro Tyr Phe Asn Leu Leu Asp Ser610 615 620Gln Glu Gln Lys Lys Val Pro Ile Pro Thr Ser Gly Val Leu Ile Ser625 630 635 640Glu Lys Leu Ala Ser Tyr Tyr Lys Val Lys Pro Gly Asp Gln Leu Val645 650 655Leu Thr Asp Arg Lys Gly Gln Ser Tyr Lys Val Thr Ile Lys Gln Val660 665 670Ile Asp Met Thr Val Gly His Tyr Leu Ile Met Ser Asp Thr Tyr Phe675 680 685Lys Asn His Phe Lys Gly Leu Glu Ala Ala Pro Ala Tyr Leu Ile Lys690 695 700Val Lys Asp Lys Asp Ser Lys His Ile Lys Glu Thr Ala Ser Asp Leu705 710 715 720Leu Thr Leu Lys Ala Ile Arg Ala Val Ser Gla Asn Val Asn His Ile725 730 735Lys Ser Val Gln Leu Val ValThr Ser Leu Asn Gln Val Met Thr Leu740 745 750Leu Val Phe Leu Ser Ile Leu Leu Ala Ile Val Ile Leu Tyr Asn Leu755 760 765Thr Thr Ile Asn Ile Ala Glu Arg Ile Arg Glu Leu Ser Thr Ile Lys770 775 780Val Leu Gly Phe Tyr Asp Gln Glu Val Thr Leu Tyr Ile Tyr Arg Glu785 790 795 800
Thr Ile Ser Leu Ser Leu Val Gly Ile Leu Leu Gly Ile Tyr Leu Gly805 810 815Lys Gly Leu His Thr Tyr Ile Met Thr Met Ile Ser Thr Gly Asp Ile820 825 830Gln Phe Gly Val Lys Val Asp Ala Tyr Val Tyr Leu Val Pro Ile Leu835 840 845Val Ile Leu Ser Leu Leu Ala Val Leu Gly Ile Trp Val Asn Arg His850 855 860Leu Lys Lys Val Asp Met Leu Glu Ala Leu Lys Ser Ile Asp865 870 875<210>43<211>1344<212>DNA<213>酿脓链球菌<400>43atgatgttaa cgaaggggca acttccctat agtgctgctt ttacaacagg agggctcttt 60tactttgtta tcattgcatt aagttattat ttgggatcga cactttggct agtctttgtt 120caggtgtttt gtttttactt atctggttta tatctttata aactcattaa ttatatgaca 180ggctttcaaa aagtggcttt aactttttca attagctact atttattatc tgttagtctt 240ggttttgggg gattgtatcc tactcaactg gctatgccat ttatattaat atcggcttgg 300tttttaacta agtattttgc ctgtttagtg aaagatgagg catttattct ttttggcttt 360gtaggtgctc ttgcaatgct aattgacccg agtaccctta tcttttggtc ttttgcttgt 420gtgacagttt tttcttataa tataagccaa aagcatcttg caagaggttt ttatcaactg 480ctagcttcga tttttggaat gattttagtt ttttacacag caggatattt cattttgaac 540ttacaagtgc taaatcctta tttatcacaa acgatgattt atccttttac tttttttaaa 600tcaggaaact tatcgttgct ttttggactg gctattcagt tgttcttcgc tttggggctt 660ggtcttttga cgggaatgga gaatgtcatt aggcgattta aaaacaattc tgatagggtc 720gtcaagtggc tatttgtcat ggtcattcta gaatctatac ttgtggctat attttcacaa 780gactatcgcc cctatcatct tttacctctt ttaccttttg gattaatttt gactgctatt 840cctgttggct atcagtatgg tataggatta ggtcagagta gtcatcgcag acgtcatggt 900aaaaatggtg ttggtcgagt aatgatgatt tatcttaaga gacactttta tttgccaatt 960ttaattgtag ggacaatact aatctgttct acttattgtt tcattagtag tattcctctt 1020aatcaggagc gtgatcatat tgctagttat ttagaacaga aactaaataa aactcaatct 1080atttatgttt gggatgatac ttctaaaatt tatttggaca gtaaagctaa atctgtttct 1140caatttagtt ctcctgacat caatacgcaa aaagagagtc atcgaaaaat attagaagat 1200gaactattag aaaataaggc tgcttatatc gttgttaatc gctataaaaa cctgcctaaa 1260atcattcaaa aagtattatc tactaattac aaagtagata aacagataac gacaaaaagt 1320tttattgttt atcagaaaaa gtaa1344
<210>44<211>447<212>PRT<213>酿脓链球菌<400>44Met Met Leu Thr Lys Gly Gln Leu Pro Tyr Ser Ala Ala Phe Thr Thr1 5 10 15Gly Gly Leu Phe Tyr Phe Val Ile Ile Ala Leu Ser Tyr Tyr Leu Gly20 25 30Ser Thr Leu Trp Leu Val Phe Val Gln Val Phe Cys Phe Tyr Leu Ser35 40 45Gly Leu Tyr Leu Tyr Lys Leu Ile Asn Tyr Met Thr Gly Phe Gln Lys50 55 60Val Ala Leu Thr Phe Ser Ile Ser Tyr Tyr Leu Leu Ser Val Ser Leu65 70 75 80Gly Phe Gly Gly Leu Tyr Pro Thr Gln Leu Ala Met Pro Phe Ile Leu85 90 95Ile Ser Ala Trp Phe Leu Thr Lys Tyr Phe Ala Cys Leu Val Lys Asp100 105 110Glu Ala Phe Ile Leu Phe Gly Phe Val Gly Ala Leu Ala Met Leu Ile115 120 125Asp Pro Ser Thr Leu Ile Phe Trp Ser Phe Ala Cys Val Thr Val Phe130 135 140Ser Tyr Asn Ile Ser Gln Lys His Leu Ala Arg Gly Phe Tyr Gln Leu145 150 155 160Leu Ala Ser Ile Phe Gly Met Ile Leu Val Phe Tyr Thr Ala Gly Tyr165 170 175Phe Ile Leu Asn Leu Gln Val Leu Asn Pro Tyr Leu Ser Gln Thr Met180 185 190Ile Tyr Pro Phe Thr Phe Phe Lys Ser Gly Asn Leu Ser Leu Leu Phe195 200 205Gly Leu Ala Ile Gln Leu Phe Phe Ala Leu Gly Leu Gly Leu Leu Thr210 215 220Gly Met Glu Asn Val Ile Arg Arg Phe Lys Asn Asn Ser Asp Arg Val
225 230 235 240Val Lys Trp Leu Phe Val Met Val Ile Leu Glu Ser Ile Leu Val Ala245 250 255Ile Phe Ser Gln Asp Tyr Arg Pro Tyr His Leu Leu Pro Leu Leu Pro260 265 270Phe Gly Leu Ile Leu Thr Ala Ile Pro Val Gly Tyr Gln Tyr Gly Ile275 280 285Gly Leu Gly Gln Ser Ser His Arg Arg Arg His Gly Lys Asn Gly Val290 295 300Gly Arg Val Met Met Ile Tyr Leu Lys Arg His Phe Tyr Leu Pro Ile305 310 315 320Leu Ile Val Gly Thr Ile Leu Ile Cys Ser Thr Tyr Cys Phe Ile Ser325 330 335Ser Ile Pro Leu Asn Gln Glu Arg Asp His Ile Ala Ser Tyr Leu Glu340 345 350Gln Lys Leu Asn Lys Thr Gln Ser Ile Tyr Val Trp Asp Asp Thr Ser355 360 365Lys Ile Tyr Leu Asp Ser Lys Ala Lys Ser Val Ser Gln Phe Ser Ser370 375 380Pro Asp Ile Asn Thr Gln Lys Glu Ser His Arg Lys Ile Leu Glu Asp385 390 395 400Glu Leu Leu Glu Asn Lys Ala Ala Tyr Ile Val Val Asn Arg Tyr Lys405 410 415Asn Leu Pro Lys Ile Ile Gln Lys Val Leu Ser Thr Asn Tyr Lys Val420 425 430Asp Lys Gln Ile Thr Thr Lys Ser Phe Ile Val Tyr Gln Lys Lys435 440 445<210>45<211>324<212>DNA<213>酿脓链球菌<400>45
atgcagtttt tacaaaaatg gtttaaacac tctaaaaaag agaagttgaa agaatcctcg 60tcccttagta cagaaataga accttctgaa aactgggcaa agattcccgc ttatattcct 120gcagacaaaa gtgattacaa aaaggttact ttaattacca gtgttattgc tgctgggcga 180tagacctaat agtcaattca aggttaaacg cattctcaag cgcaatcctg aggcaatcac 240tgtttcttta attgcttcaa gtatcgctgc aggtgtttac ccagaaagtc agtttcgggt 300gacatccatc tattgcaaaa gtaa324<210>46<211>107<212>PRT<213>酿脓链球菌<400>46Met Gln Phe Leu Gln Lys Trp Phe Lys His Ser Lys Lys Glu Lys Leu1 5 10 15Lys Glu Ser Ser Pro Leu Ser Thr Glu Ile Glu Pro Ser Glu Asn Trp20 25 30Glu Lys Ile Pro Ala Tyr Ile Pro Ala Asp Lys Ser Asp Tyr Lys Lys35 40 45Val Thr Leu Ile Thr Ser Ala Ile Ala Ala Gly Asp Arg Pro Asn Ser50 55 60Gln Phe Lys Val Lys Arg Ile Leu Lys Arg Asn Pro Glu Ala Ile Thr65 70 75 80Val Ser Leu Ile Ala Ser Ser Ile Ala Ala Gly Val Tyr Pro Glu Ser85 90 95Gln Phe Arg Val Thr Ser Ile Tyr Cys Lys Arg100 105<210>47<211>288<212>DNA<213>酿脓链球菌<400>47atgacaaaac gtaattcaaa agcctatata ttatggcaaa aaattatcaa aattttagga 60attattgcac taattggtac ttttttcctc gctttttggc tgtatagact aggtatatta 120aacgatagta atgctcttaa agacttagtg cagcgctata gattatgggg gccgtttgtt 180tttattgtcg tgcagatcat acagattgtt tttcctgtga ttcctggagg ccttacgaca 240gttgcaggtt ttttaatctt tggcccctgt aacaggtttt atttataa 288
<210>48<211>95<212>PRT<213>酿脓链球菌<400>48Met Thr Lys Arg Asn Ser Lys Ala Tyr Ile Leu Trp Gln Lys Ile Ile1 5 10 15Lys Ile Leu Gly Ile Ile Ala Leu Ile Gly Thr Phe Phe Leu Ala Phe20 25 30Trp Leu Tyr Arg Leu Gly Ile Leu Asn Asp Ser Asn Ala Leu Lys Asp35 40 45Leu Val Gln Arg Tyr Arg Leu Trp Gly Pro Phe Val Phe Ile Val Val50 55 60Gln Ile Ile Gln Ile Val Phe Pro Val Ile Pro Gly Gly Leu Thr Thr65 70 75 80Val Ala Gly Phe Leu Ile Phe Gly Pro Cys Asn Arg Phe Tyr Leu85 90 95<210>49<211>1311<212>DNA<213>酿脓链球菌<400>49atgaataaat taaaaaaaga gattttatca gataactata accacttttt tcattttttt 60gcggttttta caggtatttt tgtcattatg actattatta tcttacagat tatgcggttt 120ggcgtttatt cgtcagttga cagtagttta gtttctgtta gtaataatgc aagtagctat 180gctaatcgta cgatggctag aatatcttct ttttactttg atactgaaaa taacattatt 240aaggcgctgc ctgattcaga tagttctaag ttattaggaa cgcctgcagc taatacagat 300atcattttgt ttagtgctaa tggaacaatt ttaaatgctt ttgatgcgtt ttctaactat 360caaaattttc atttagataa acgccggttg gggagtattg aaaccaccag tttaatgaat 420ttttatggac aagaagaaaa ataccatacg ataactgtag gggttcatat caaaaattat 480cctgcagttg cctatatgat ggcagtagta aatgtggaac aattagaccg cgctaatgaa 540cgttatgagc gcattattat tatagttatg agtgtttttt ggctaatttc tattttagca 600agtatttatt tagccaagtg gagcagaaaa cctattttag aaagctatga aaaacaaaaa 660atgtttgttg aaaatgctag tcatgaatta aggacccctt tggcggtctt acagaatcgt 720ctggaatcgc tttttcgtaa gcccaacgaa acgatattag aaaatagtga gcatctcgct 780tctagtttag acgaggttcg caacatgcgc atcttaacaa ctaatttatt aaatttagca 840agacgagatg atggcattaa tccacagtgg actcatttag atacagattt ttttaatgct 900atttttgaga attatgaact agttgctaaa gaatatggaa aaatatttta ttttcagaac 960
caagtcaata gatcgttaag aatggataag gctttactaa aacaattaat aacgatttta 1020tttgacaatg ctattaaata tacagataaa aatggtatta ttgaaattat agtgaaaaca 1080acggacaaaa atttattaat ttctgttatt gataatggtc cagggataac agatgaagaa 1140aagaaaaaga tttttgatcg tttttatcga gttgacaaag ctagaacacg gcaaacaggt 1200ggatttggct tggggttggc tttagctcag caaatcgtga tgtctttaaa aggaaatatt 1260acagtaaagg ataatgatcc taaaggtagt atttttgaag tcaaactata a 1311<210>50<211>436<212>PRT<213>酿脓链球菌<400>50Met Asn Lys Leu Lys Lys Glu Ile Leu Ser Asp Asn Tyr Asn His Phe1 5 10 15Phe His Phe Phe Ala Val Phe Thr Gly Ile Phe Val Ile Met Thr Ile20 25 30Ile Ile Leu Gln Ile Met Arg Phe Gly Val Tyr Ser Ser Val Asp Ser35 40 45Ser Leu Val Ser Val Ser Asn Asn Ala Ser Ser Tyr Ala Asn Arg Thr50 55 60Met Ala Arg Ile Ser Ser Phe Tyr Phe Asp Thr Glu Asn Asn Ile Ile65 70 75 80Lys Ala Leu Pro Asp Ser Asp Ser Ser Lys Leu Leu Gly Thr Pro Ala85 90 95Ala Asn Thr Asp Ile Ile Leu Phe Ser Ala Asn Gly Thr Ile Leu Asn100 105 110Ala Phe Asp Ala Phe Ser Asn Tyr Gln Asn Phe His Leu Asp Lys Arg115 120 125Arg Leu Gly Ser Ile Glu Thr Thr Ser Leu Met Asn Phe Tyr Gly Gln130 135 140Glu Glu Lys Tyr His Thr Ile Thr Val Gly Val His Ile Lys Asn Tyr145 150 155 160Pro Ala Val Ala Tyr Met Met Ala Val Val Asn Val Glu Gln Leu Asp165 170 175Arg Ala Asn Glu Arg Tyr Glu Arg Ile Ile Ile Ile Val Met Ser Val180 185 190
Phe Trp Leu Ile Ser Ile Leu Ala Ser Ile Tyr Leu Ala Lys Trp Ser195 200 205Arg Lys Pro Ile Leu Glu Ser Tyr Glu Lys Gln Lys Met Phe Val Glu210 215 220Asn Ala Ser His Glu Leu Arg Thr Pro Leu Ala Val Leu Gln Asn Arg225 230 235 240Leu Glu Ser Leu Phe Arg Lys Pro Asn Glu Thr Ile Leu Glu Asn Ser245 250 255Glu His Leu Ala Ser Ser Leu Asp Glu Val Arg Asn Met Arg Ile Leu260 265 270Thr Thr Asn Leu Leu Asn Leu Ala Arg Arg Asp Asp Gly Ile Asn Pro275 280 285Gln Trp Thr His Leu Asp Thr Asp Phe Phe Asn Ala Ile Phe Glu Asn290 295 300Tyr Glu Leu Val Ala Lys Glu Tyr Gly Lys Ile Phe Tyr Phe Gln Asn305 310 315 320Gln Val Asn Arg Ser Leu Arg Met Asp Lys Ala Leu Leu Lys Gln Leu325 330 335Ile Thr Ile Leu Phe Asp Asn Ala Ile Lys Tyr Thr Asp Lys Asn Gly340 345 350Ile Ile Glu Ile Ile Val Lys Thr Thr Asp Lys Asn Leu Leu Ile Ser355 360 365Val Ile Asp Asn Gly Pro Gly Ile Thr Asp Glu Glu Lys Lys Lys Ile370 375 380Phe Asp Arg Phe Tyr Arg Val Asp Lys Ala Arg Thr Arg Gln Thr Gly385 390 395 400Gly Phe Gly Leu Gly Leu Ala Leu Ala Gln Gln Ile Val Met Ser Leu405 410 415Lys Gly Asn Ile Thr Val Lys Asp Asn Asp Pro Lys Gly Ser Ile Phe420 425 430Glu Val Lys Leu435
<210>51<211>699<212>DNA<213>酿脓链球菌<400>51atgttttctg gacatcaact aaaaacagca cgattatcaa agggaataac tcaatcagaa 60ttgggaagat tgttgcatgt caataaaatg acaatatcta attgggaaaa aggtaagaat 120ataccaaatg aaaaacattt aaatgcctta ttgcatctat tcaatgtgac atctgattat 180ttcgacccaa actatagatt gctaacgcct tataaccagc tgacaatatc taataaagaa 240aaagtaattg gctattcaga gcgattgtta aatcatcaaa tagacaaaaa atctaaagat 300ctcatagata aaccatcaca attatatgct tatcgggtct atgaaagttt atctgctggt 360actggttact cctattttgg tgatggtaac tttgatgttg tcttttacga tgaacaatta 420gaatacgatt ttgcgtcttg ggtttttgga gattctatgg agccaactta tttaaatggt 480gaagttgttc ttataaaaca aaatagtttt gattacgatg gagcaattta tgcagtcgaa 540tgggatgggc aaacatatat caaaaaggta tttcgtgaag atgagggatt acgtctagtg 600tccttaaata aaaaatattc tgataagttt gctccctata gcgaagaacc tcgcattatt 660ggcaaaatta tcgctaattt taggccctta gaaatttaa699<210>52<211>232<212>PRT<213>酿脓链球菌<400>52Met Phe Ser Gly His Gln Leu Lys Thr Ala Arg Leu Ser Lys Gly Ile1 5 10 15Thr Gln Ser Glu Leu Gly Arg Leu Leu His Val Asn Lys Met Thr Ile20 25 30Ser Asn Trp Glu Lys Gly Lys Asn Ile Pro Asn Glu Lys His Leu Asn35 40 45Ala Leu Leu His Leu Phe Asn Val Thr Ser Asp Tyr Phe Asp Pro Asn50 55 60Tyr Arg Leu Leu Thr Pro Tyr Asn Gln Leu Thr Ile Ser Asn Lys Glu65 70 75 80Lys Val Ile Gly Tyr Ser Glu Arg Leu Leu Asn His Gln Ile Asp Lys85 90 95Lys Ser Lys Asp Leu Ile Asp Lys Pro Ser Gln Leu Tyr Ala Tyr Arg100 105 110
Val Tyr Glu Ser Leu Ser Ala Gly Thr Gly Tyr Ser Tyr Phe Gly Asp115 120 125Gly Asn Phe Asp Val Val Phe Tyr Asp Glu Gln Leu Glu Tyr Asp Phe130 135 140Ala Ser Trp Val Phe Gly Asp Ser Met Glu Pro Thr Tyr Leu Asn Gly145 150 155 160Glu Val Val Leu Ile Lys Gln Asn Ser Phe Asp Tyr Asp Gly Ala Ile165 170 175Tyr Ala Val Glu Trp Asp Gly Gln Thr Tyr Ile Lys Lys Val Phe Arg180 185 190Glu Asp Glu Gly Leu Arg Leu Val Ser Leu Asn Lys Lys Tyr Ser Asp195 200 205Lys Phe Ala Pro Tyr Ser Glu Glu Pro Arg Ile Ile Gly Lys Ile Ile210 215 220Ala Asn Phe Arg Pro Leu Glu Ile225 230<210>53<211>1497<212>DNA<213>酿脓链球菌<400>53ttgaaaaggg ttcccgtaga aagagacaaa cgcttagtct ctttcttttt ctttcttctc 60atttctgtta taataagtca ggtaactaca ttagaaagat ttgtgggtct gtcatctaag 120agatgtcatt cccgaagagg tattagtgac ttgtctcaat caactgcaac ttatattaat 180gttattggag ctgggctagc tggttctgaa gctgcctatc agattgctaa gcgcggtatc 240cccgttaaat tgtatgaaat gcgtggtgtc aaagcaacac cgcaacataa aaccactaat 300tttgccgaat tggtctgttc caactcattt cgtggtgata gcttaaccaa tgcagtcggt 360cttctcaaag aagaaatgcg gcgattagac tccattatta tgcgtaatgg tgaagctaac 420cgcgtacctg ctgggggagc aatggctgtt gaccgtgagg ggtatgcaga gagtgtcact 480gcagagttgg aaaatcatcc tctcattgag gtcattcgtg gtgaaattac agaaatccct 540gacgatgcta tcacggttat cgcgacggga ccgctgactt cggatgccct ggcagaaaaa 600attcacgcgc taaatggtgg cgacggattc tatttttacg atgcagcagc gcctatcatt 660gataaatcta ccattgatat gagcaaggtt taccttaaat ctcgctacga taaaggcgaa 720gctgcttacc tcaactgccc tatgaccaaa gaagaattca tggctttcca tgaagctctg 780acaaccgcag aagaagcccc gctgaatgcc tttgaaaaag aaaagtattt tgaaggctgt 840atgccgattg aagttatggc taaacgtggc attaaaacca tgctttatgg acctatgaaa 900cccgttggat tggaatatcc agatgactat acaggtcctc gcgatggaga atttaaaacg 960ccatatgccg tcgtgcaatt gcgtcaagat aatgcagctg gaagccttta taatatcgtt 1020
ggtttccaaa cccatctcaa atggggtgag caaaaacgcg ttttccaaat gattccaggg 1080cttgaaaatg ctgagtttgt ccgctacggc gtcatgcatc gcaattccta tatggattca 1140ccaaatcttt taaccgaaac cttccaatct cggagcaatc caaacctttt ctttgcaggt 1200cagatgactg gagttgaagg ttatgtcgaa tcagctgctt caggtttagt agcaggaatc 1260aatgctgctc gtttgttcaa aagagaagaa gcacttattt ttcctcagac aacagctatt 1320gggagtttgc ctcattatgt gactcatgcc gacagtaagc atttccaacc aatgaacgtc 1380aactttggca tcatcaaaga gttagaaggc ccacgcattc gtgacaaaaa agaacgttat 1440gaagctattg ctagtcgtgc tttggcagat ttagacacct gcttagcgtc gctttaa1497<210>54<211>498<212>PRT<213>酿脓链球菌<400>54Leu Lys Arg Val Pro Val Glu Arg Asp Lys Arg Leu Val Ser Phe Phe1 5 10 15Phe Phe Leu Leu Ile Ser Val Ile Ile Ser Gln Val Thr Thr Leu Glu20 25 30Arg Phe Val Gly Leu Ser Ser Lys Arg Cys His Ser Arg Arg Gly Ile35 40 45Ser Asp Leu Ser Gln Ser Thr Ala Thr Tyr Ile Asn Val Ile Gly Ala50 55 60Gly Leu Ala Gly Ser Glu Ala Ala Tyr Gln Asn Ala Lys Arg Gly Ile65 70 75 80Pro Val Lys Leu Tyr Glu Met Arg Gly Val Lys Ala Thr Pro Gln His85 90 95Lys Thr Thr Asn Phe Ala Glu Leu Val Cys Ser Asn Ser Phe Arg Gly100 105 110Asp Ser Leu Thr Asn Ala Val Gly Leu Leu Lys Glu Glu Met Arg Arg115 120 125Leu Asp Ser Ile Ile Met Arg Asn Gly Glu Ala Asn Arg Val Pro Ala130 135 140Gly Gly Ala Met Ala Val Asp Arg Glu Gly Tyr Ala Glu Ser Val Thr145 150 155 160Ala Glu Leu Glu Asn His Pro Leu Ile Glu Val Ile Arg Gly Glu Ile165 170 175
Thr Glu Ile Pro Asp Asp Ala Ile Thr Val Ile Ala Thr Gly Pro Leu180 185 190Thr Ser Asp Ala Leu Ala Glu Lys Ile His Ala Leu Asn Gly Gly Asp195 200 205Gly Phe Tyr Phe Tyr Asp Ala Ala Ala Pro Ile Ile Asp Lys Ser Thr210 215 220Ile Asp Met Ser Lys Val Tyr Leu Lys Ser Arg Tyr Asp Lys Gly Glu225 230 235 240Ala Ala Tyr Leu Asn Cys Pro Met Thr Lys Glu Glu Phe Met Ala Phe245 250 255His Glu Ala Leu Thr Thr Ala Glu Glu Ala Pro Leu Asn Ala Phe Glu260 265 270Lys Glu Lys Tyr Phe Glu Gly Cys Met Pro Ile Glu Val Met Ala Lys275 280 285Arg Gly Ile Lys Thr Met Leu Tyr Gly Pro Met Lys Pro Val Gly Leu290 295 300Glu Tyr Pro Asp Asp Tyr Thr Gly Pro Arg Asp Gly Glu Phe Lys Thr305 310 315 320Pro Tyr Ala Val Val Gln Leu Arg Gln Asp Asn Ala Ala Gly Ser Leu325 330 335Tyr Asn Ile Val Gly Phe Gln Thr His Leu Lys Trp Gly Glu Gln Lys340 345 350Arg Val Phe Gln Met Ile Pro Gly Leu Glu Asn Ala Glu Phe Val Arg355 360 365Tyr Gly Val Met His Arg Asn Ser Tyr Met Asp Ser Pro Asn Leu Leu370 375 380Thr Glu Thr Phe Gln Ser Arg Ser Asn Pro Asn Leu Phe Phe Ala Gly385 390 395 400Gln Met Thr Gly Val Glu Gly Tyr Val Glu Ser Ala Ala Ser Gly Leu405 410 415Val Ala Gly Ile Asn Ala Ala Arg Leu Phe Lys Arg Glu Glu Ala Leu420 425 430Ile Phe Pro Gln Thr Thr Ala Ile Gly Ser Leu Pro His Tyr Val Thr
435 440 445His Ala Asp Ser Lys His Phe Gln Pro Met Asn Val Asn Phe Gly Ile450 455 460Ile Lys Glu Leu Glu Gly Pro Arg Ile Arg Asp Lys Lys Glu Ara Tyr465 470 475 480Glu Ala Ile Ala Ser Arg Ala Leu Ala Asp Leu Asp Thr Cys Leu Ala485 490 495Ser Leu<210>55<211>1539<212>DNA<213>酿脓链球菌<400>55atgattaagg atatgattga cagtattgag cagtttgctc agacacaggc tgattttcca 60gtttatgatt gtttagggga acgccgcact tacggacaac tcaaaagaga ttctgatagc 120attgctgcat ttatagatag cttagcttta ctggcaaaat ctccagtttt ggtttttggg 180gcgcaaactt atgatatgtt agctactttt gtagctttaa ccaaatctgg tcatgcctat 240atcccagtag atgtgcattc agcaccagaa cgtattttag cgattattga gattgcaaag 300cccagtttaa tcattgctat tgaggaattc cctcttacta ttgaagggat ttcccttgtc 360tcactatcag agattgagtc agcaaaatta gcagaaatgc cctatgagcg aacacattct 420gttaaaggag atgataatta ttacattatt ttcacctctg gaacaacggg ccaaccaaaa 480ggggtgcaaa tttcacatga caatcttttg agctttacca actggatgat cgaagatgca 540gcatttgatg tacctaaaca gccacaaatg ctggcgcagc caccctattc ctttgacctt 600tctgtcatgt actgggcacc taccttggct ttaggtggaa ccttatttgc acttccaaaa 660gaattggtgg cagactttaa acagttattt acaacgattg cgcaacttcc agttggcatt 720tggacatcga ctccttcatt tgctgatatg gccatgctta gcgatgattt ttgccaggct 780aagatgccag ctttaacgca tttttatttt gatggcgaag aattaaccgt ttctacggct 840cgaaaactct ttgaacgttt cccgagtgcc aagattatca atgcctatgg accaacagaa 900gcgactgtag ccttatccgc tattgaaatt accagagaaa tggtggataa ttatacccgc 960ttgccgattg gctaccccaa accagattct ccgacctata ttattgatga agatggtaag 1020gagttatctt caggggagca gggtgaaatt attgttacag ggcctgctgt gtcaaaaggt 1080tacctcaaca atcctgagaa aaccgcagaa gctttcttta cttttaaagg acagcctgct 1140tatcatacag gggacattgg ctcactgaca gaagataata ttttgttgta tggtgggcgt 1200ttggattttc agattaaata tgctggttat cgtattgaac tagaagatgt ttcccaacag 1260ttgaatcaat caccaatggt agcatcggct gtggctgttc caaggtacaa taaagaacat 1320aaggttcaaa atctcttggc ctatatcgtt gtcaaagatg gggttaaaga gcgttttgat 1380agggaattgg agttaaccaa agctatcaaa gcctctgtta aggatcatat gatgagttat 1440atgatgcctt ctaagtttct ttatcgagat agtctaccat taactccaaa tggtaagata 1500gatattaaaa ctttgattaa tgaggtcaat aaccgataa1539
<210>56<211>512<212>PRT<213>酿脓链球菌<400>56Met Ile Lys Asp Met Ile Asp Ser Ile Glu Gln Phe Ala Gln Thr Gln1 5 10 15Ala Asp Phe Pro Val Tyr Asp Cys Leu Gly Glu Arg Arg Thr Tyr Gly20 25 30Gln Leu Lys Arg Asp Ser Asp Ser Ile Ala Ala Phe Ile Asp Ser Leu35 40 45Ala Leu Leu Ala Lys Ser Pro Val Leu Val Phe Gly Ala Gln Thr Tyr50 55 60Asp Met Leu Ala Thr Phe Val Ala Leu Thr Lys Ser Gly His Ala Tyr65 70 75 80Ile Pro Val Asp Val His Ser Ala Pro Glu Arg Ile Leu Ala Ile Ile85 90 95Glu Ile Ala Lys Pro Ser Leu Ile Ile Ala Ile Glu Glu Phe Pro Leu100 105 110Thr Ile Glu Gly Ile Ser Leu Val Ser Leu Ser Glu Ile Glu Ser Ala115 120 125Lys Leu Ala Glu Met Pro Tyr Glu Arg Thr His Ser Val Lys Gly Asp130 135 140Asp Asn Tyr Tyr Ile Ile Phe Thr Ser Gly Thr Thr Gly Gln Pro Lys145 150 155 160Gly Val Gln Ile Ser His Asp Asn Leu Leu Ser Phe Thr Asn Trp Met165 170 175Ile Glu Asp Ala Ala Phe Asp Val Pro Lys Gln Pro Gln Met Leu Ala180 185 190Gln Pro Pro Tyr Ser Phe Asp Leu Ser Val Met Tyr Trp Ala Pro Thr195 200 205Leu Ala Leu Gly Gly Thr Leu Phe Ala Leu Pro Lys Glu Leu Val Ala210 215 220
Asp Phe Lys Gln Leu Phe Thr Thr Ile Ala Gln Leu Pro Val Gly Ile225 230 235 240Trp Thr Ser Thr Pro Ser Phe Ala Asp Met Ala Met Leu Ser Asp Asp245 250 255Phe Cys Gln Ala Lys Met Pro Ala Leu Thr His Phe Tyr Phe Asp Gly260 265 270Glu Glu Leu Thr Val Ser Thr Ala Arg Lys Leu Phe Glu Arg Phe Pro275 280 285Ser Ala Lys Ile Ile Asn Ala Tyr Gly Pro Thr Glu Ala Thr Val Ala290 295 300Leu Ser Ala Ile Glu Ile Thr Arg Glu Met Val Asp Asn Tyr Thr Arg305 310 315 320Leu Pro Ile Gly Tyr Pro Lys Pro Asp Ser Pro Thr Tyr Ile Ile Asp325 330 335Glu Asp Gly Lys Glu Leu Ser Ser Gly Glu Gln Gly Glu Ile Ile Val340 345 350Thr Gly Pro Ala Val Ser Lys Gly Tyr Leu Asn Asn Pro Glu Lys Thr355 360 365Ala Glu Ala Phe Phe Thr Phe Lys Gly Gln Pro Ala Tyr His Thr Gly370 375 380Asp Ile Gly Ser Leu Thr Glu Asp Asn Ile Leu Leu Tyr Gly Gly Arg385 390 395 400Leu Asp Phe Gln Ile Lys Tyr Ala Gly Tyr Arg Ile Glu Leu Glu Asp405 410 415Val Ser Gln Gln Leu Asn Gln Ser Pro Met Val Ala Ser Ala Val Ala420 425 430Val Pro Arg Tyr Asn Lys Glu His Lys Val Gln Asn Leu Leu Ala Tyr435 440 445Ile Val Val Lys Asp Gly Val Lys Glu Arg Phe Asp Arg Glu Leu Glu450 455 460Leu Thr Lys Ala Ile Lys Ala Ser Val Lys Asp His Met Met Ser Tyr465 470 475 480Met Met Pro Ser Lys Phe Leu Tyr Arg Asp Ser Leu Pro Leu Thr Pro
485 490 495Asn Gly Lys Ile Asp Ile Lys Thr Leu Ile Asn Glu Val Asn Asn Arg500 505 510<210>57<211>1278<212>DNA<213>酿脓链球菌<400>57atgacaaaaa ctaatcttaa ctggagcggt ttttcaaaga aaacattcga agaacgcctc 60caacttatcg aaaaatttaa actacttaat gctgaaaact taaatcaact caaaacagac 120gttcttttgc ctatccaaac agctaatcaa atgactgaaa atgtcttagg acgattggct 180ttgcccttta gcatagctcc tgattttctt gtcaacggtt caacttatca gatgcctttt 240gtcacggaag aaccttctgt tgttgctgca gcatctttcg cagcaaaact aatcaaacgc 300tcaggtggtt ttaaagctca aaccctaaac cgacaaatga ttggtcaaat tgttctttac 360gatatcgacc aaatagataa cgctaaagcc gccatccttc ataaaacaaa aaagctaatt 420gcattggcaa ataaagctta tccttccatt gttaaaagag gtggaggcgc tagaaccatt 480catttggaag aaaaaggaga atttttgatt ttctatctga ctgttgatac ccaagaagct 540atgggagcaa atatggtcaa tactatgatg gaagctcttg ttcctgattt aacaagactg 600tctaaggggc attgtctaat ggcgatttta tctaattacg caacagagtc gcttgttact 660actagttgtg agattcccgt gcgcctttta gatcacgata aaacaaaatc cctacagtta 720gctcaaaaaa tagagctagc cagccgacta gctcaagtag atccttaccg ggctactact 780cataataaag gtatttttaa tggcattgat gcagtggtaa tagccacagg aaatgactgg 840cgtgctattg aagcaggggc ccatgcttat gcctcaagaa atggtagcta tcaaggactt 900agtcagtggc attttgacca agataaacaa gttctgcttg gccaaatgac cctccctatg 960cctattgcta gtaagggggg atctatcggg cttaacccta ctgtttctat cgcacatgat 1020cttcttaatc aacctgatgc caaaacatta gcccaattga ttgcatctgt ggggttagct 1080caaaactttg ctgcactaaa agctctgacc tcatctggca tccaagctgg tcacatgaaa 1140ctacatgcga aatcattagc tcttttggcg ggggcaaccc aagacgaaat tgctccttta 1200gttaatgctt tactagctga taaaccaata aatctagaaa aagcacattt ttacttatcc 1260cagctaagac agtcttaa 1278<210>58<211>425<212>PRT<213>酿脓链球菌<400>58Met Thr Lys Thr Asn Leu Asn Trp Ser Gly Phe Ser Lys Lys Thr Phe1 5 10 15
Glu Glu Arg Leu Gln Leu Ile Glu Lys Phe Lys Leu Leu Asn Ala Glu20 25 30Asn Leu Asn Gln Leu Lys Thr Asp Val Leu Leu Pro Ile Gln Thr Ala35 40 45Asn Gln Met Thr Glu Asn Val Leu Gly Arg Leu Ala Leu Pro Phe Ser50 55 60Ile Ala Pro Asp Phe Leu Val Asn Gly Ser Thr Tyr Gln Met Pro Phe65 70 75 80Val Thr Glu Glu Pro Ser Val Val Ala Ala Ala Ser Phe Ala Ala Lys85 90 95Leu Ile Lys Arg Ser Gly Gly Phe Lys Ala Gln Thr Leu Asn Arg Gln100 105 110Met Ile Gly Gln Ile Val Leu Tyr Asp Ile Asp Gln Ile Asp Asn Ala115 120 125Lys Ala Ala Ile Leu His Lys Thr Lys Lys Leu Ile Ala Leu Ala Asn130 135 140Lys Ala Tyr Pro Ser Ile Val Lys Arg Gly Gly Gly Ala Arg Thr Ile145 150 155 160His Leu Glu Glu Lys Gly Glu Phe Leu Ile Phe Tyr Leu Thr Val Asp165 170 175Thr Gln Glu Ala Met Gly Ala Asn Met Val Asn Thr Met Met Glu Ala180 185 190Leu Val Pro Asp Leu Thr Arg Leu Ser Lys Gly His Cys Leu Met Ala195 200 205Ile Leu Ser Asn Tyr Ala Thr Glu Ser Leu Val Thr Thr Ser Cys Glu210 215 220Ile Pro Val Arg Leu Leu Asp His Asp Lys Thr Lys Ser Leu Gln Leu225 230 235 240Ala Gln Lys Ile Glu Leu Ala Ser Arg Leu Ala Gln Val Asp Pro Tyr245 250 255Arg Ala Thr Thr His Asn Lys Gly Ile Phe Asn Gly Ile Asp Ala Val260 265 270Val Ile Ala Thr Gly Asn Asp Trp Arg Ala Ile Glu Ala Gly Ala His
275 280 285Ala Tyr Ala Ser Arg Asn Gly Ser Tyr Gln Gly Leu Ser Gln Trp His290 295 300Phe Asp Gln Asp Lys Gln Val Leu Leu Gly Gln Met Thr Leu Pro Met305 310 315 320Pro Ile Ala Ser Lys Gly Gly Ser Ile Gly Leu Asn Pro Thr Val Ser325 330 335Ile Ala His Asp Leu Leu Asn Gln Pro Asp Ala Lys Thr Leu Ala Gln340 345 350Leu Ile Ala Ser Val Gly Leu Ala Gln Asn Phe Ala Ala Leu Lys Ala355 360 365Leu Thr Ser Ser Gly Ile Gln Ala Gly His Met Lys Leu His Ala Lys370 375 380Ser Leu Ala Leu Leu Ala Gly Ala Thr Gln Asp Glu Ile Ala Pro Leu385 390 395 400Val Asn Ala Leu Leu Ala Asp Lys Pro Ile Asn Leu Glu Lys Ala His405 410 415Phe Tyr Leu Ser Gln Leu Arg Gln Ser420 425<210>59<211>915<212>DNA<213>酿脓链球菌<400>59atggtattat ttacaggaaa aacagtcgaa gaagctatcg aaacaggact tcaagagtta 60gggttatcac gccttaaagc gcatatcaaa gtcatttcaa aagagaaaaa aggtttcctc 120gggtttggta aaaagccagc ccaagttgat atcgaaggta tcagcgacaa gacggtttat 180aaggctgata aaaaagccac tcgaggtgtt ccagaggata ttaatcgtca aaatactccc 240gcggtcaatt ctgctgatgt agaacctgaa gaaataaaag ccactcaaag gttagaagca 300gaagatacca aagtggttcc tctcatgtct gaagatagtc cagcgcaaac cccttctaat 360cttgctgaga cagtcactga aacaaaagca caacaaccgt caatcccagt cgaagaatca 420gaagtgcccc aagatgctgg taatgatggt ttcagcaaag atattgaaaa agctgctcag 480gaagtgtccg attatgtgac taaaattatc tatgaaatgg atatcgaagc taccgttgaa 540accagcaaca atcgtcgcca aatcaatttg cagattgaaa cgccagaggc gggacgtgtg 600attggttacc atggtaaggt cttgaaatcc ttgcagttgt tagctcaaaa tttcttgcac 660gaccgctatt caaaaaattt ttcagtatcc ttgaatgtcc atgattatgt ggaacatcga 720
acagaaacct tgattgactt tacgcaaaaa gttgccaaac gcgttttgga atctggtcaa 780gattacacca tggatcccat gagtaacagt gagcgtaaaa tcgttcataa aaccgtttca 840tccattgaag gggttgatag ttattctgaa ggcaatgacc ctaaccgcta tgtggtagtc 900agtcttcaac gttaa 915<210>60<211>304<212>PRT<213>酿脓链球菌<400>60Met Val Leu Phe Thr Gly Lys Thr Val Glu Glu Ala Ile Glu Thr Gly1 5 10 15Leu Gln Glu Leu Gly Leu Ser Arg Leu Lys Ala His Ile Lys Val Ile20 25 30Ser Lys Glu Lys Lys Gly Phe Leu Gly Phe Gly Lys Lys Pro Ala Gln35 40 45Val Asp Ile Glu Gly Ile Ser Asp Lys Thr Val Tyr Lys Ala Asp Lys50 55 60Lys Ala Thr Arg Gly Val Pro Glu Asp Ile Asn Arg Gln Asn Thr Pro65 70 75 80Ala Val Asn Ser Ala Asp Val Glu Pro Glu Glu Ile Lys Ala Thr Gln85 90 95Arg Leu Glu Ala Glu Asp Thr Lys Val Val Pro Leu Met Ser Glu Asp100 105 110Ser Pro Ala Gln Thr Pro Ser Asn Leu Ala Glu Thr Val Thr Glu Thr115 120 125Lys Ala Gln Gln Pro Ser Ile Pro Val Glu Glu Ser Glu Val Pro Gln130 135 140Asp Ala Gly Asn Asp Gly Phe Ser Lys Asp Ile Glu Lys Ala Ala Gln145 150 155 160Glu Val Ser Asp Tyr Val Thr Lys Ile Ile Tyr Glu Met Asp Ile Glu165 170 175Ala Thr Val Glu Thr Ser Asn Asn Arg Arg Gln Ile Asn Leu Gln Ile180 185 190Glu Thr Pro Glu Ala Gly Arg Val Ile Gly Tyr His Gly Lys Val Leu
195 200 205Lys Ser Leu Gln Leu Leu Ala Gln Asn Phe Leu His Asp Arg Tyr Ser210 215 220Lys Asn Phe Ser Val Ser Leu Asn Val His Asp Tyr Val Glu His Arg225 230 235 240Thr Glu Thr Leu Ile Asp Phe Thr Gln Lys Val Ala Lys Arg Val Leu245 250 255Glu Ser Gly Gln Asp Tyr Thr Met Asp Pro Met Ser Asn Ser Glu Arg260 265 270Lys Ile Val His Lys Thr Val Ser Ser Ile Glu Gly Val Asp Ser Tyr275 280 285Ser Glu Gly Asn Asp Pro Asn Arg Tyr Val Val Val Ser Leu Gln Arg290 295 300<210>61<211>1269<212>DNA<213>酿脓链球菌<400>61atgacaacaa aatatcaaac aatcatttcc aatatcgaac aagatatcca gaaacagcga 60ctaaaaaaag gggacaagct accttcaatt agggtactaa gtaaggttta ttattgtagc 120aaagatactg ttcagcgggc tcttttagaa ttaaaatatc gtcacttaat ttatgctgtt 180cctaaaagtg gttattatgt tttgggtaac gtaagcatgc ccgataatgt tcttaatcta 240agtcttgaag attataataa tatggcttat gaagatttcc gactctgctt aaatgaggcc 300ttaagtgcta aagacaaata cctctttcat tattatcaca aaaccgaagg actagaagaa 360ctaagggaag ctttgcttct ttacttagct gaaaatagtg tttacagtaa caaagaccaa 420ctattaatca cctctgggac gcaacaagcg ctttatattt tatcacaaat gccttttcct 480aatacgggca aaacaattct ccttgaaaag cctacttatc atcggatgga agctattgtt 540gctcagttag gattacccta tcaaactatc tctagacact ttaatggcct tgatttagaa 600ctcttagaat ctttatttca aactggcgat attaaatttt tttacacgat ttcacgattt 660tcacatcctc tgggactttc ttatagcact aaggaaaagg aagctattgt tcgtctagca 720caacgatacc aggtttatat tttagaagat gattatttag gagattttgt gaaacttaaa 780gagccaccaa ttcattatta tgacactcat caccgaatca tctacctaaa atctttttca 840atgagtgttt ttcctgcact ccgtatcgga gctctagttt taccgtcagg tttaaaacct 900cattttttaa cccaaaaatc attgattgat ttagacacga acttactaat gcaaaaagca 960ttagctcttt atttagaaaa tgggatgttt caaaaaaatc ttcgctttat taagcgttat 1020ctaaaacagc gggaacgtca attggctctc tttttaaaac aaaattgccc tgatattcac 1080
tatcaactaa cccctactca tttagtgatt gattacacga catcagactc ttatagaaac 1140tttacattag ataaatctga tagaataata ataactggaa aaaaacgcta tctctctatt 1200actatcaatc aacaaataca aagcaaatta aactcactaa tcaaaaatac ttgtggaaag 1260agcaactaa 1269<210>62<211>422<212>PRT<213>酿脓链球菌<400>62Met Thr Thr Lys Tyr Gln Thr Ile Ile Ser Asn Ile Glu Gln Asp Ile1 5 10 15Gln Lys Gln Arg Leu Lys Lys Gly Asp Lys Leu Pro Ser Ile Arg Val20 25 30Leu Ser Lys Val Tyr Tyr Cys Ser Lys Asp Thr Val Gln Arg Ala Leu35 40 45Leu Glu Leu Lys Tyr Arg His Leu Ile Tyr Ala Val Pro Lys Ser Gly50 55 60Tyr Tyr Val Leu Gly Asn Val Ser Met Pro Asp Asn Val Leu Asn Leu65 70 75 80Ser Leu Glu Asp Tyr Asn Asn Met Ala Tyr Glu Asp Phe Arg Leu Cys85 90 95Leu Asn Glu Ala Leu Ser Ala Lys Asp Lys Tyr Leu Phe His Tyr Tyr100 105 110His Lys Thr Glu Gly Leu Glu Glu Leu Arg Glu Ala Leu Leu Leu Tyr115 120 125Leu Ala Glu Asn Ser Val Tyr Ser Asn Lys Asp Gln Leu Leu Ile Thr130 135 140Ser Gly Thr Gln Gln Ala Leu Tyr Ile Leu Ser Gln Met Pro Phe Pro145 150 155 160Asn Thr Gly Lys Thr Ile Leu Leu Glu Lys Pro Thr Tyr His Arg Met165 170 175Glu Ala Ile Val Ala Gln Leu Gly Leu Pro Tyr Gln Thr Ile Ser Arg180 185 190His Phe Asn Gly Leu Asp Leu Glu Leu Leu Glu Ser Leu Phe Gln Thr
195 200 205Gly Asp Ile Lys Phe Phe Tyr Thr Ile Ser Arg Phe Ser His Pro Leu210 215 220Gly Leu Ser Tyr Ser Thr Lys Glu Lys Glu Ala Ile Val Arg Leu Ala225 230 235 240Gln Arg Tyr Gln Val Tyr Ile Leu Glu Asp Asp Tyr Leu Gly Asp Phe245 250 255Val Lys Leu Lys Glu Pro Pro Ile His Tyr Tyr Asp Thr His His Arg260 265 270Ile Ile Tyr Leu Lys Ser Phe Ser Met Ser Val Phe Pro Ala Leu Arg275 280 285Ile Gly Ala Leu Val Leu Pro Ser Gly Leu Lys Pro His Phe Leu Thr290 295 300Gln Lys Ser Leu Ile Asp Leu Asp Thr Asn Leu Leu Met Gln Lys Ala305 310 315 320Leu Ala Leu Tyr Leu Glu Asn Gly Met Phe Gln Lys Asn Leu Arg Phe325 330 335Ile Lys Arg Tyr Leu Lys Gln Arg Glu Arg Gln Leu Ala Leu Phe Leu340 345 350Lys Gln Asn Cys Pro Asp Ile His Tyr Gln Leu Thr Pro Thr His Leu355 360 365Val Ile Asp Tyr Thr Thr Ser Asp Ser Tyr Arg Asn Phe Thr Leu Asp370 375 380Lys Ser Asp Arg Ile Ile Ile Thr Gly Lys Lys Arg Tyr Leu Ser Ile385 390 395 400Thr Ile Asn Gln Gln Ile Gln Ser Lys Leu Asn Ser Leu Ile Lys Asn405 410 415Thr Cys Gly Lys Ser Asn420
权利要求
1.用于治疗或诊断的肽，其是由包括任何如下所示来自酿脓链球菌的核苷酸序列的操纵子编码的SEQ ID NO.1，3，5，7，9，11，13，15，17，19，21，23，27，29，31，33，35，37，39，41，43，45，47，49，51，53，55，57，59和61，或革兰氏阳性细菌中在肽水平或核苷酸水平上有至少40％序列相似性或同一性的相关分子，或其功能片段。
2.根据权利要求1的肽，其中所述序列相似性或同一性为至少60％。
3.根据权利要求1或2的肽，其中所述序列相似性或同一性为至少90％。
4.根据权利要求1的肽，其包含如下所示的氨基酸序列SEQ ID NO.2，4，6，8，10，12，14，16，18，20，22，24，28，30，32，34，36，38，40，42，44，46，48，50，52，54，56，58，60或62。
5.用于治疗或诊断的编码根据任何前述权利要求的肽的多核苷酸。
6.一种宿主，其经转化表达根据权利要求1到4任一项的肽。
7.一种减毒微生物，其包含破坏权利要求1中定义的任何核苷酸序列表达的突变。
8.根据权利要求7的微生物，其中突变是插入失活或基因缺失。
9.根据权利要求7或8的微生物，其中所述微生物是A群链球菌。
10.根据权利要求7到9中任一项的微生物，其用于治疗或诊断。
11.根据权利要求7到10中任一项的微生物，其在另一个核苷酸序列中包含突变。
12.根据权利要求7到11中任一项的微生物，其包含异源抗原、治疗性肽或核酸。
13.一种疫苗，其包含根据权利要求1到4中任一项的肽，或其表达方式。
14.一种疫苗，其包含根据权利要求7到12中任一项的微生物。
15.根据权利要求1到12中任一项的产品的用途，其用于生产用于治疗或预防与链球菌或革兰氏阳性菌感染有关的病症的药物。
16.根据权利要求15的用途，其中所述病症是肺炎。
17.根据权利要求15或16的用途，其用于兽医治疗。
18.一种抗体，其针对根据权利要求1到4中任一项的肽而产生。
19.根据权利要求1到12中任一项的产品的用途，其用于鉴定抗微生物药物的筛选试验。
全文摘要
显示了来自酿脓链球菌的一系列基因编码涉及毒力的产物。因此鉴定这些基因可以制备减毒微生物。此外，所述基因或其编码产物能用于生产治疗用的疫苗。
文档编号C12Q1/68GK1804039SQ20051012972
公开日2006年7月19日 申请日期2000年12月22日 优先权日1999年12月23日
发明者E·E·克拉克, 周立庆, J·E·谢伊, R·G·费尔德曼, D·W·霍尔登 申请人:瓦马克斯有限公司