CN107310856B - 提供过水解酶催化反应的系统 - Google Patents

提供过水解酶催化反应的系统 Download PDF

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CN107310856B
CN107310856B CN201710526382.5A CN201710526382A CN107310856B CN 107310856 B CN107310856 B CN 107310856B CN 201710526382 A CN201710526382 A CN 201710526382A CN 107310856 B CN107310856 B CN 107310856B
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T.J.博伊德
徐国锋
R.亚当斯
R.皮尔斯
D.萨马鲁
D.维斯乔
K.A.富泽
R.迪科西莫
H.王
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Colgate Palmolive Co
EIDP Inc
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EI Du Pont de Nemours and Co
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Abstract

本文描述了用于存贮和分配多部分牙齿增白制剂的套装，其包含经配置以形成两个或更多个密封室的可变形材料，例如，其中第一室含有包含具有过水解活性的酶的低粘度液体溶液，第二室含有过氧化物源和至少一种酰基供体底物。还提供了利用该原理的具体的多部分牙齿增白制剂及其使用方法。

Description

提供过水解酶催化反应的系统
本申请是原案申请日为2012年12月18日、原案申请号为201280070107.2 (国际申请号为PCT/US2012/070367)、发明名称为“提供过水解酶催化反应的系统”的专利申请的分案申请。
相关申请的交叉引用
本申请要求2011年12月19日提交的美国申请号61/577,529的优先权，其通过引用以其整体结合到本文中。
发明背景
通常需要使制剂组分在使用前分隔开，因为例如所述组分如果混合，则可能太不稳定而不便于长期贮存。在这种情况下，需要在接近使用时能够以有效又简单的方式将制剂组分混合。
可能需要保持制剂组分分隔开的制剂的一个实例是牙齿增白制剂，其包含反应性成分例如过氧化物或过氧酸或其前体。例如，可能希望将A+B或A+B+C混合以得到不稳定的漂白剂X，但是将A和B保持分隔开直到该时间点。问题出现了，因为在使用期间，混合必须迅速，漂白剂X向牙齿表面的扩散必须是有效的。遗憾的是，混合多种凝胶或其它中等粘性材料一般不是迅速混合化学品的有效方法；如果特定消费者用手混合，则可能产生样品混合良好和混合差的区域。不得不将两种粘性建筑用漆一起进行人工搅拌时，才容易发现以下问题：层流引起颜色存在于相邻条纹中，而不是有效地将两种颜色混在一起。为了直接克服这个问题，可能需要比愿意专注于该项任务的特定使用者更多的时间和混合努力，并且当反应物类X在数分钟内开始分解时，这种方法将难以实施。
因此需要允许成分在接近使用时有效率且有效果地混合的产品。
发明概述
本发明提供多室系统，其中一个室含有低粘度液体溶液，另一个室含有液体、粉料或粉料混合物，各室被易碎的或可撕开的屏障分隔开，使得在挤压一个室时，屏障破碎，各室的组分可混合形成溶液、乳液、悬浮液或可挤出凝胶，其可通过第二室的出口分配，其中低粘度液体溶液包含具有过水解酶(perhydrolase)活性的蛋白质，其含有碳水化合物酯酶家族7签名基序(signature motif)，而且另一个室或多个室含有酰基供体，例如羧酸酯和过氧化物源，使得在各室内容物混合时，具有过水解酶活性的蛋白质催化由过氧化物源释放的过氧化物和酰基供体之间的反应，形成过酸。当涂覆在牙齿上时，所述过酸对漂白牙齿是十分有效的，使得可在较短的时间内并以较低的过氧化物水平实现有效的漂白作用。
在一个具体实施方案中，一个室含有包含具有过水解活性的蛋白质(即家族7碳水化合物酯酶)的低粘度水溶液，另一个室含有均为粉末形式的胶凝剂、过氧化物和羧酸酯化合物，使得当屏障破碎且允许各室内容物混合时，过氧化物和羧酸酯可发生由过水解酶催化的反应，在由液体和胶凝剂形成的可挤出凝胶中形成过酸，然后可例如使用托盘或条，将所述可挤出凝胶挤出并涂覆在牙齿上持续足够的时间(例如10-30分钟)，以漂白牙齿。
本发明实用性的更多方面从下文提供的详细描述来看将是显然的。应了解，详细描述和具体实施例虽然表明本发明的优选实施方案，但是仅仅旨在说明目的，并无意限制本发明的范围。
生物序列简述
下列序列遵循37 C.F.R. §§ 1.821-1.825 (“Requirements for PatentApplications Containing Nucleotide Sequences and/or Amino Acid SequenceDisclosures - the Sequence Rules (含核苷酸序列和/或氨基酸序列公开内容的专利申请规定—序列法则)”)，并且与世界知识产权组织(World Intellectual PropertyOrganization，WIPO)标准ST.25 (2009)、欧洲专利公约(European Patent Convention，EPC)的序列表规定、专利合作条约(Patent Cooperation Treaty，PCT)规则5.2和49.5(a-bis)以及行政指令(Administrative Instructions)的第208节和附件C一致。核苷酸和氨基酸序列数据所用符号和格式遵循37 C.F.R. § 1.822中提供的法则。
SEQ ID NO: 1是海栖热袍菌(Thermotoga maritima) C277S变异过水解酶的氨基酸序列。
SEQ ID NO: 2是包含与牙结合域(tooth binding domain) (在Butterick等人的国际专利申请公布号WO2012/087970A2中亦称为“EZ-7”)偶联的海栖热袍菌C277S变异过水解酶的融合蛋白的氨基酸序列。
SEQ ID NO: 3是编码来自枯草芽孢杆菌(Bacillus subtilis) ATCC® 31954™的头孢菌素C脱乙酰酶的核酸序列。
SEQ ID NO: 4是来自枯草芽孢杆菌ATCC® 31954™的头孢菌素C脱乙酰酶的氨基酸序列。
SEQ ID NO: 5是来自枯草芽孢杆菌枯草亚种(Bacillus subtilis subsp.subtilis)菌株168的头孢菌素C脱乙酰酶的氨基酸序列。
SEQ ID NO: 6是来自枯草芽孢杆菌ATCC®6633™的头孢菌素C脱乙酰酶的氨基酸序列。
SEQ ID NO: 7是地衣芽孢杆菌(B. licheniformis) ATCC® 14580™的头孢菌素C脱乙酰酶的氨基酸序列。
SEQ ID NO: 8是来自短小芽孢杆菌(B. pumilus) PS213的乙酰木聚糖酯酶的氨基酸序列。
SEQ ID NO: 9是来自热解纤维梭菌(Clostridium thermocellum) ATCC®27405™的乙酰木聚糖酯酶的氨基酸序列。
SEQ ID NO: 10是来自那不勒斯栖热袍菌(Thermotoga neapolitana)的乙酰木聚糖酯酶的氨基酸序列。
SEQ ID NO: 11是来自海栖热袍菌MSB8的乙酰木聚糖酯酶的氨基酸序列。
SEQ ID NO: 12是来自热厌氧杆菌属菌种(Thermoanaerobacterium sp.) JW/SLYS485的乙酰木聚糖酯酶的氨基酸序列。
SEQ ID NO: 13是来自耐盐芽孢杆菌(Bacillus halodurans) C-125的头孢菌素C脱乙酰酶的氨基酸序列。
SEQ ID NO: 14是来自克劳氏芽孢杆菌(Bacillus clausii) KSM-K16头孢菌素C脱乙酰酶的氨基酸序列。
SEQ ID NO: 15是来自美国专利申请公布号2010-0087529 (通过引用以其整体结合到本文中)的那不勒斯栖热袍菌乙酰木聚糖酯酶变体的氨基酸序列，其中277位的Xaa残基为Ala、Val、Ser或Thr。
SEQ ID NO: 16是美国专利申请公布号2010-0087529的海栖热袍菌MSB8乙酰木聚糖酯酶变体的氨基酸序列，其中277位的Xaa残基为Ala、Val、Ser或Thr。
SEQ ID NO: 17是来自美国专利申请公布号2010-0087529的莱廷格栖热袍菌(Thermotoga lettingae)乙酰木聚糖酯酶变体的推导的氨基酸序列，其中277位的Xaa残基为Ala、Val、Ser或Thr。
SEQ ID NO: 18是来自美国专利申请公布号2010-0087529的嗜石油栖热袍菌(Thermotoga petrophila)乙酰木聚糖酯酶变体的氨基酸序列，其中277位的Xaa残基为Ala、Val、Ser或Thr。
SEQ ID NO: 19是衍生于来自美国专利申请公布号2010-0087529的“RQ2(a)”的栖热袍菌属菌种(Thermotoga sp.) RQ2乙酰木聚糖酯酶变体的氨基酸序列，其中277位的Xaa残基为Ala、Val、Ser或Thr。
SEQ ID NO: 20是衍生于来自美国专利申请公布号2010-0087529的“RQ2(b)”的栖热袍菌属菌种RQ2乙酰木聚糖酯酶变体的氨基酸序列，其中278位的Xaa残基为Ala、Val、Ser或Thr。
SEQ ID NO: 21是莱廷格栖热袍菌乙酰木聚糖酯酶的氨基酸序列。
SEQ ID NO: 22是嗜石油栖热袍菌乙酰木聚糖酯酶的氨基酸序列。
SEQ ID NO: 23是来自称为“RQ2(a)”的栖热袍菌属菌种RQ2的第一乙酰木聚糖酯酶的氨基酸序列。
SEQ ID NO: 24是来自称为“RQ2(b)”的栖热袍菌属菌种RQ2的第二乙酰木聚糖酯酶的氨基酸序列。
SEQ ID NO: 25是解糖热厌氧杆菌(Thermoanearobacterium saccharolyticum)头孢菌素C脱乙酰酶的氨基酸序列。
SEQ ID NO: 26是来自乳酸乳球菌(Lactococcus lactis)的乙酰木聚糖酯酶的氨基酸序列(GENBANK®登录号ABX75634.1)。
SEQ ID NO: 27是来自百脉根中间根瘤菌(Mesorhizobium loti)的乙酰木聚糖酯酶的氨基酸序列(GENBANK®登录号BAB53179.1)。
SEQ ID NO: 28是来自嗜热脂肪土芽孢杆菌(Geobacillus stearothermophilus)的乙酰木聚糖酯酶的氨基酸序列(GENBANK®登录号AAF70202.1)。
SEQ ID NO: 29-163是对口腔表面具有亲和力的肽的氨基酸序列。
SEQ ID NO: 164-177是肽接头/间隔基的氨基酸序列。
SEQ ID NO: 178-197是各种靶向过水解酶融合构建体的氨基酸序列，所述构建体包含通过肽接头与对口腔表面具有亲和力的结合域偶联的过水解酶(参见Butterick等人的国际专利申请公布号WO2012/087970A2)。
附图简述
根据详细描述和附图，将更全面地理解本发明，附图中：
图1表示本发明的一个实施方案，其是本发明的两室套装(package)，该套装在周边(1)周围是热封的，具有被易碎密封片(seal) (3)分隔的含有液体组分的第一室(2)和包含粉料组分的第二室(4)，使得当挤压第一室(2)时，易碎密封片(3)破裂，液体流进第二室(4)中并与粉料混合，所得混合物然后可通过破坏划痕缘(5)使混合物流出或挤出喷嘴(6)来分配。
图2表示本发明的另一个实施方案，如图1所示，允许在临用前混合各组分，但利用具有喷嘴的三室套装，消费者可打开所述喷嘴以分配产品。在该实施方案中，套装包含第一室(7)、第二室(8)、第三室(9)和喷嘴，各室被易碎密封片(3)分隔，喷嘴具有断开头(6)以分配混合后的材料。
发明详述
下面优选实施方案的描述本质上只是示例性的，绝无意限制本发明、其应用或用途。
本文所用术语“底物”、“合适的底物”、“酰基供体”和“羧酸酯底物”可互换地具体指：
(a) 一种或多种具有以下结构的酯
[X]mR5
其中
X为式R6C(O)O的酯基；
R6为被羟基或C1-C4烷氧基任选取代的C1-C7直链、支链或环状烃基部分，其中在R6为C2-C7时，R6任选包含一个或多个醚键；
R5为被羟基任选取代的C1-C6直链、支链或环状烃基部分或5元环状杂芳族部分或6元环状芳族或杂芳族部分；其中R5中的每个碳原子各自包含不超过一个羟基或不超过一个酯基，且其中R5任选包含一个或多个醚键；
m为1至R5中的碳原子数的整数，
所述一种或多种酯在25℃下在水中具有至少5 ppm的溶解度；或
(b) 具有以下结构的一种或多种甘油酯
Figure DEST_PATH_IMAGE001
其中R1为被羟基或C1-C4烷氧基任选取代的C1-C7直链或支链烷基，R3和R4各自为H或R1C(O)；或
(c) 下式的一种或多种酯
Figure DEST_PATH_IMAGE002
其中R1为被羟基或C1-C4烷氧基任选取代的C1-C7直链或支链烷基，R2为C1-C10直链或支链烷基、烯基、炔基、芳基、烷基芳基、烷基杂芳基、杂芳基、(CH2CH2O)n或(CH2CH(CH3)-O)nH，n为1-10；或
(d) 一种或多种乙酰化单糖、乙酰化双糖或乙酰化多糖；或
(e) (a)至(d)的任何组合。
本文所用术语“过酸”与过氧酸(peroxyacid)、过氧羧酸、过氧酸(peroxy acid)、过羧酸和过氧酸(peroxoic acid)同义。
本文所用术语“过乙酸”缩写为“PAA”，并且与过氧乙酸、乙烷过氧酸和CAS登记号79-21-0的所有其它同义词同义。
本文所用术语“一醋精”与单乙酸甘油酯、丙三醇单乙酸酯和甘油单乙酸酯同义。
本文所用术语“二醋精”与二乙酸甘油酯、丙三醇二乙酸酯、甘油二乙酸酯和CAS登记号25395-31-7的所有其它同义词同义。
本文所用术语“三醋精”与丙三醇三乙酸酯、甘油三乙酸酯、三乙酸甘油酯、1,2,3-三乙酰氧基丙烷、1,2,3-丙三醇三乙酸酯和CAS登记号102-76-1的所有其它同义词同义。
本文所用术语“乙酰化糖(acetylated sugar)”和“乙酰化糖(acetylatedsaccharide)”是指包含至少一个乙酰基的单糖、双糖和多糖。实例包括但不限于葡萄糖五乙酸酯、木糖四乙酸酯、乙酰化木聚糖、乙酰化木聚糖片段、β-D-呋喃核糖-1,2,3,5-四乙酸酯、三-O-乙酰基-D-半乳醛和三-O-乙酰基-己烯糖。
本文所用术语“烃基”、“烃基基团”和“烃基部分”意指通过碳-碳单键、双键或三键和/或通过醚键连接并相应地被氢原子取代的碳原子的直链、支链或环状排列。这类烃基可以是脂族和/或芳族的。烃基的实例包括甲基、乙基、丙基、异丙基、丁基、异丁基、叔丁基、环丙基、环丁基、戊基、环戊基、甲基环戊基、己基、环己基、苄基和苯基。在一个优选的实施方案中，烃基部分是通过碳-碳单键和/或通过醚键连接并相应地被氢原子取代的碳原子的直链、支链或环状排列。
本文所用术语1,2-乙二醇、1,2-丙二醇、1,3-丙二醇、1,2-丁二醇、1,3-丁二醇、2,3-丁二醇、1,4-丁二醇、1,2-戊二醇、2,5-戊二醇、1,5-戊二醇、1,6-戊二醇、1,2-己二醇、2,5-己二醇、1,6-己二醇的“单酯”和“二酯”及其混合物是指所述化合物包含至少一个式RC(O)O的酯基，其中R为C1-C7直链烃基部分。在一个实施方案中，羧酸酯底物选自丙二醇二乙酸酯(PGDA)、乙二醇二乙酸酯(EDGA)及其混合物。
本文所用术语“丙二醇二乙酸酯”与1,2-二乙酰氧基丙烷、亚丙基二乙酸酯(propylene diacetate)、1,2-丙二醇二乙酸酯和CAS登记号623-84-7的所有其它同义词同义。
本文所用术语“乙二醇二乙酸酯”与1,2-二乙酰氧基乙烷、亚乙基二乙酸酯、甘醇二乙酸酯和CAS登记号111-55-7的所有其它同义词同义。
本文所用术语“合适的酶促反应混合物”、“合适的反应组分”、“合适的水性反应混合物”、“反应混合物”和“产过酸组分”是指其中反应物和过水解酶催化剂接触的原料和水。产过酸组分可至少包括：具有过水解活性的酶，其中过水解酶是至少一种CE-7过水解酶(任选呈靶向身体表面的融合蛋白的形式)；至少一种合适的羧酸酯底物；过氧(peroxygen)源；和水。
本文所用术语“过水解(perhydrolysis)”定义为选定底物与过氧化物反应形成过酸。通常，无机过氧化物在催化剂存在下与选定底物反应以产生过氧羧酸。本文所用术语“化学过水解”包括其中底物(过氧羧酸前体)与过氧化氢源混合的过水解反应，其中过氧羧酸在没有酶催化剂时形成。本文所用术语“酶促过水解”包括其中羧酸酯底物(过酸前体；“酰基供体”)与过氧化氢源和水混合从而酶催化剂催化过酸形成的过水解反应。
本文所用术语“过水解酶活性”是指每单位质量(例如毫克)的蛋白质、细胞干重或固定化催化剂重量的催化剂活性。
如本文所用，“1单位酶活性”或“1单位活性”或“U”定义为在规定温度下每分钟产生1 μmol过氧羧酸产品所需要的过水解酶活性的量。
本文所用术语“酶催化剂”和“过水解酶催化剂”是指包含具有过水解活性的酶的催化剂，并且可以是呈完整微生物细胞、透化微生物细胞、微生物细胞提取物的一种或多种细胞组分、部分纯化的酶或纯化的酶的形式。酶催化剂还可经化学修饰(例如通过聚乙二醇化或通过与交联试剂反应)。还可采用本领域技术人员熟知的方法，将过水解酶催化剂固定在可溶或不溶支持体上；参见例如Immobilization of Enzymes and Cells; Gordon F.Bickerstaff编辑; Humana Press, Totowa, NJ, USA; 1997。
如本文所用，“乙酰木聚糖酯酶”是指催化乙酰化木聚糖和其它乙酰化糖类脱乙酰的酶(E.C. 3.1.1.72；AXE)。
本文所用术语“头孢菌素C脱乙酰酶”和“头孢菌素C乙酰水解酶”是指催化头孢菌素类例如头孢菌素C和7-氨基头孢霉烷酸(cephalosporanic acid)脱乙酰的酶(E.C.3.1.1.41) (Mitsushima等(1995) Appl. Env. Microbiol. 61(6):2224-2229)。本文提供了具有显著的过水解活性的几种头孢菌素C脱乙酰酶的氨基酸序列。
本文所用术语“枯草芽孢杆菌ATCC® 31954TM”是指保藏在美国典型培养物保藏中心(ATCC)、国际保藏号为ATCC® 31954 TM的细菌细胞。如本文所述，来自枯草芽孢杆菌ATCC®31954 TM的具有显著过水解酶活性的酶以SEQ ID NO: 4提供(参见美国专利申请公布号2010-0041752)。
本文所用术语“海栖热袍菌MSB8”是指据报道具有乙酰木聚糖酯酶活性的细菌细胞(GENBANK® NP_227893.1；参见美国专利申请公布号2008-0176299)。来自海栖热袍菌MSB8的具有过水解酶活性的酶的氨基酸序列以SEQ ID NO: 11提供。海栖热袍菌MSB8过水解酶的变体以SEQ ID NO: 1和16提供。
如本文所用，“分离的核酸分子”、“分离的多核苷酸”和“分离的核酸片段”可互换使用，是指单链或双链的、任选含有合成的、非天然的或经改变的核苷酸碱基的RNA或DNA的聚合物。呈DNA聚合物形式的分离的核酸分子可由cDNA、基因组DNA或合成DNA的一个或多个区段组成。
术语“氨基酸”是指蛋白质或多肽的基础化学结构单元。本文使用下列缩略语识别特定的氨基酸：
Figure DEST_PATH_IMAGE003
如本文所用，“分离的核酸分子”、“分离的多核苷酸”和“分离的核酸片段”可互换使用，是指RNA或DNA的聚合物。本文所用术语“签名基序”和“诊断基序”是指为具有规定活性的酶家族所共有的保守结构。签名基序可用来定义和/或鉴定对规定的底物家族具有相似酶活性的结构上相关的酶的家族。签名基序可以是单一连续氨基酸序列或在一起形成签名基序的一系列不连续的保守基序。通常，保守基序用氨基酸序列表示。在一个实施方案中，用于本发明组合物和方法的过水解酶包含CE-7碳水化合物酯酶签名基序。
本文所用术语“序列分析软件”是指用于分析核苷酸或氨基酸序列的任何计算机算法或软件程序。“序列分析软件”可以是市售的或独立开发的。典型的序列分析软件可包括但不限于GCG程序套件(Wisconsin Package 9.0版, Accelrys Software Corp., SanDiego, CA)、BLASTP、BLASTN、BLASTX (Altschul等, J. Mol. Biol. 215:403-410(1990))和DNASTAR (DNASTAR, Inc. 1228 S. Park St. Madison, WI 53715 USA)、CLUSTALW (例如1.83版；Thompson等, Nucleic Acids Research, 22(22):4673-4680(1994))和整合Smith-Waterman算法的FASTA程序(W. R. Pearson, Comput. Methods Genome Res., [Proc. Int. Symp.] (1994), 会议日期1992, 111-20. 编辑：Suhai,Sandor. 出版商: Plenum, New York, NY)、Vector NTI (Informax, Bethesda, MD)和Sequencher 4.05版。在本申请的情况下，应了解当序列分析软件用于分析时，分析结果应基于所引用程序的“默认值”，除非另有说明。如本文所用，“默认值”将意指首次初始化时最初与软件一起加载的由软件生产商设定的任何值或参数集。
术语“身体表面”是指可用作增益剂(benefit agent)例如过酸增益剂的靶标的人体的任何表面。本发明的方法和组合物涉及口腔护理应用和产品。因此，身体表面包含口腔材料/表面。在一个实施方案中，口腔材料包含牙釉质。
本文所用术语“牙齿增白”和“牙齿漂白”可互换使用，是指改善一颗或多颗牙的亮度(例如增白)。
如本文所用，牙齿的“内源性着色”是指由釉质和下层的牙本质内的色原产生的颜色。由于釉质变薄且下层的黄色牙本质变暗所致，人牙齿本身的颜色往往随着老化变得更黄。去除内源性着色常常需要使用过氧化物或其它氧化性化学品，其渗入釉质，并使内部色原脱色。
与内源性着色不同，当外源产色材料与釉质结合时，在牙表面形成“外源性着色”，通常在天然包覆牙的薄膜内形成。大多数人随时间推移在他们的牙齿上堆积某种程度的难看的外源性着色。这种着色过程受诸如以下因素促进：(1)摄入含有鞣质的食物和饮料例如咖啡、茶或红葡萄酒；(2)使用烟草产品；和/或(3)暴露于某些阳离子物质(例如锡、铁和氯己定)。这些物质往往附着于釉质的羟磷灰石结构上，这导致牙齿变色和牙齿洁白度同时降低。在数年时间内，外源性着色可渗入釉质层，并导致内源性着色。
本文所用术语“脱色”或“脱色性”是指从口腔表面除去着色的过程。着色可以是内源性着色、外源性着色或其组合。
如本文所用，“有效量的过水解酶”是指实现在具体应用中所需的酶促活性必需的过水解酶的量。这类有效量由本领域普通技术人员容易确定，而且基于许多因素，例如所用的具体酶变体。
本文所用术语“过氧源(peroxygen source)”和“过氧来源”是指在水溶液中能够提供浓度约1 mM以上的过氧化氢的化合物，包括但不限于过氧化氢、过氧化氢加合物(例如脲-过氧化氢加合物(过氧化氢脲))、过硼酸盐和过碳酸盐。如本文所述，增白条中存在的过氧源呈颗粒的形式，其中使用者使颗粒状过氧化物颗粒水合以释放有效量的过氧化氢。如本文所述，在混合反应组分时，水性反应制剂中由过氧化合物提供的过氧化氢的浓度最初为至少0.1 mM以上。在一个实施方案中，水性反应制剂中的过氧化氢浓度为至少0.5 mM。在一个实施方案中，水性反应制剂中的过氧化氢浓度为至少1 mM。在另一个实施方案中，水性反应制剂中的过氧化氢浓度为至少10 mM。在另一个实施方案中，水性反应制剂中的过氧化氢浓度为至少100 mM。在另一个实施方案中，水性反应制剂中的过氧化氢浓度为至少200mM。在另一个实施方案中，水性反应制剂中的过氧化氢浓度为500 mM以上。在又一个实施方案中，水性反应制剂中的过氧化氢浓度为1000 mM以上。制剂中过氧化氢与酶底物例如甘油三酯(H2O2:底物)的摩尔比率可为约0.002-20，优选约0.1-10，最优选约0.1-1。
本文所用术语“寡糖”是指含有通过糖苷键连接的2和至少24单糖单元之间的化合物。术语“单糖”是指经验式(CH2O)n的化合物，其中n≥3，碳骨架是不分枝的，除一个以外各个碳原子含有羟基，所述剩余的碳原子是在碳原子1上的醛或酮。术语“单糖”另指胞内环状半缩醛或半缩酮形式。
本文所用术语“能水合的胶粘剂”可指能够被水合的粘性材料。能水合的胶粘剂基本是干的和无粘着力的直到水合。在水合时，能水合的胶粘剂变得足够粘着以结合牙表面。
本文所用术语“有效量”可指实现所需作用必需的材料的量。
本文所用术语“基本上无粘着力直到水合”可指在水合前没有足以粘附于牙齿表面的粘合强度。
所谓“序列同一性”是指应用例如一般描述于以下文献的序列比对程序例如ClustalW或BLAST得到的氨基酸同一性：Altschul SF, Gish W, Miller W, Myers EW,Lipman DJ, "Basic local alignment search tool", J Mol Biol (1990) 215 (3):403–410；以及Goujon M, McWilliam H, Li W, Valentin F, Squizzato S, Paern J,Lopez R, Nucleic Acids Research (2010) 38 Suppl: W695-9。
用于本发明的例如在与过氧化物反应时形成过酸的酰基供体选自以下的一种或多种：(i)被羟基和/或C1-4烷氧基任选取代的C2-18羧酸，例如C2-6羧酸(例如乙酸)，包括低级直链或支链烷基羧酸；(ii)其可水解和可接受的酯(例如甘油单酯、甘油二酯和甘油三酯和酰化糖类)和(iii)其混合物。例如，酰基供体包括1,2,3-三乙酰氧基丙烷(本文有时称为三醋精或丙三醇三乙酸酯)和酰化糖类，例如乙酰化糖类。在一个具体实施方案中，用于该用途的酯可为例如在25℃下在水中具有至少5 ppm的溶解度的酯。
酰基供体和/或酶可任选被胶囊化。有多种本领域已知的天然和合成的胶囊化选择。改性淀粉和阿拉伯树胶是特别适当的，因为它们是食品级，相对便宜，快速溶解，并且可吸收相当高水平的液体油。需要考虑对最终粘度的任何影响。
在一些实施方案中，颗粒包含能够使神经脱敏或闭合牙本质小管的抗致敏剂(antisensitivity agent)。在一些实施方案中，抗致敏剂选自钾离子源、硅酸盐、亚锡离子源、碱性氨基酸、粘土及其组合。在一些实施方案中，钾离子源是口腔可接受的钾盐，并以有效降低牙本质敏感性的量存在。在一些实施方案中，钾离子源选自氯化钾、硝酸钾及其组合。在一些实施方案中，碱性氨基酸为精氨酸。在一些实施方案中，碱性氨基酸选自磷酸精氨酸、精氨酸重碳酸盐和盐酸精氨酸。在一些实施方案中，硅酸盐为硅酸钙。
CE-7过水解酶
本发明的组合物和方法包含具有过水解活性的酶，该酶在结构上归类为酶的碳水化合物家族酯酶家族7 (CE-7家族)的成员(参见Coutinho, P.M., Henrissat, B.“Carbohydrate-active enzymes: an integrated database approach (碳水化合物活性酶：集成数据库方法)”载于Recent Advances in Carbohydrate Bioengineering, H.J.Gilbert, G. Davies, B. Henrissat和B. Svensson编辑, (1999) The Royal Societyof Chemistry, Cambridge, 第3-12页)。已证实酶的CE-7家族在与过氧源混合时，从各种羧酸酯底物产生过氧羧酸特别有效(DiCosimo等人的美国专利7,794,378、7,951,566、7,723,083和7,964,378和美国专利申请公布号2008-0176299、2010-0087529、2011-0081693和2011-0236335；各通过引用结合到本文中)。
CE-7家族的成员包括头孢菌素C脱乙酰酶(CAH；E.C. 3.1.1.41)和乙酰木聚糖酯酶(AXE；E.C. 3.1.1.72)。CE-7酯酶家族的成员共有保守签名基序(Vincent等, J. Mol. Biol., 330:593-606 (2003))。包含CE-7签名基序(“CE-7过水解酶”)和/或基本相似结构的过水解酶适用于本文所述组合物和方法。鉴定基本相似的生物分子的方法是本领域众所周知的(例如序列比对方案、核酸杂交和/或保守签名基序的存在情况)。一方面，过水解酶包括包含CE-7签名基序和与本文提供的序列之一有以下氨基酸同一性的酶：至少20%、优选至少30%、更优选至少33%、更优选至少40%、更优选至少42%、更优选至少50%、更优选至少60%、更优选至少70%、更优选至少80%、更优选至少90%和最优选至少90%、91%、92%、93%、94%、95%、96%、97%、98%或99%。
如本文所用，短语“酶在结构上被归类为CE-7酶”、“CE-7过水解酶”或“在结构上归类为碳水化合物酯酶家族7酶”可用来指在结构上归类为CE-7碳水化合物酯酶的具有过水解活性的酶。该酶家族可通过签名基序的存在来界定(Vincent等，同上)。CE-7酯酶的签名基序包含以下3个保守基序(残基位置编号相对于参比序列SEQ ID NO: 1；海栖热袍菌过水解酶的C277S变体)。
Arg118-Gly119-Gln120；
Gly186-Xaa187-Ser188-Gln189-Gly190；和
His303-Glu304。
通常，氨基酸残基第187位的Xaa为甘氨酸、丙氨酸、脯氨酸、色氨酸或苏氨酸。属于催化三联体的3个氨基酸残基中的两个用黑体字表示。在一个实施方案中，氨基酸残基第187位的Xaa选自甘氨酸、丙氨酸、脯氨酸、色氨酸和苏氨酸。
CE-7碳水化合物酯酶家族内保守基序的进一步分析表明存在可用于进一步界定属于CE-7碳水化合物酯酶家族的过水解酶的其它保守基序(SEQ ID NO: 1氨基酸第272-274位的LXD)。在又一个实施方案中，上文界定的签名基序可包括如下界定的其它(第四个)保守基序：
Leu272-Xaa273-Asp274。
氨基酸残基第273位的Xaa通常为异亮氨酸、缬氨酸或甲硫氨酸。第四基序包括属于催化三联体(Ser188-Asp274-His303)的天冬氨酸残基(黑体字)。
CE-7过水解酶可为具有至少一个肽组分的融合蛋白的形式，所述肽组分对至少一种身体表面具有亲和力。在一个实施方案中，用来确定靶向过水解酶(融合蛋白)是否包含CE-7签名基序的所有比对将根据不含对身体表面具有亲和力的肽组分的过水解酶的氨基酸序列。
许多众所周知的全局比对算法(即序列分析软件)可用来比对表示具有过水解酶活性的酶的两个或更多个氨基酸序列以确定该酶是否包含本发明的签名基序。将比对序列与参比序列(SEQ ID NO: 1)进行比较以确定签名基序的存在。在一个实施方案中，使用参比氨基酸序列(如本文所用的过水解酶序列(SEQ ID NO: 1))的CLUSTAL比对(例如CLUSTALW)用来鉴定属于CE-7酯酶家族的过水解酶。保守氨基酸残基的相对编号基于参比氨基酸序列的残基编号以说明比对序列内小的插入或缺失(例如通常5个氨基酸以内)。
可用来鉴定包含本发明签名基序的序列(当与参比序列相比时)的其它适合算法的实例包括但不限于Needleman和Wunsch (J. Mol. Biol. 48, 443-453 (1970)；一种全局比对工具)和Smith-Waterman (J. Mol. Biol. 147:195-197 (1981)；一种局部比对工具)。在一个实施方案中，Smith-Waterman比对使用默认参数执行。合适的默认参数的实例包括利用BLOSUM62评分矩阵，其GAP开放罚分=10，GAP延伸罚分=0.5。
在一个实施方案中，合适的过水解酶包括包含CE-7签名基序和与SEQ ID NO: 1有以下氨基酸同一性的酶：至少20%、优选至少30%、33%、40%、50%、60%、70%、80%、85%、90%、91%、92%、93%、94%、95%、96%、97%、98%或99%。
具有过水解活性的合适CE-7碳水化合物酯酶的实例包括但不限于具有例如SEQID NO: 1和4-28的氨基酸序列的酶。在一个实施方案中，酶包含选自1、10、11、15和16的氨基酸序列。
本文所用术语“CE-7变体”、“变异过水解酶”或“变体”可指当与衍生变体的相应酶(通常野生型酶)相比时，具有导致至少一个氨基酸添加、缺失和/或取代的遗传修饰的CE-7过水解酶；只要保持CE-7签名基序和相关过水解活性。CE-7变异过水解酶也可用于本发明的组合物和方法。CE-7变体的实例以SEQ ID NO: 1、15、16、17、18、19和20提供。在一个实施方案中，变体可包括SEQ ID NO: 1和16。
技术人员认知到基本相似的CE-7过水解酶序列(保留签名基序)也可用于本发明的组合物和方法。在一个实施方案中，基本相似的序列通过其与本文所列举序列相关的核酸分子在高严格性条件下杂交的能力界定。在另一个实施方案中，序列比对算法可用来根据与本文提供的DNA或氨基酸序列的百分比同一性来界定基本相似的酶。
如本文所用，核酸分子当第一分子的单链在适当的温度和溶液离子强度条件下可与其它分子退火时，该核酸分子与另一核酸分子(例如cDNA、基因组DNA或RNA)是可杂交的。杂交和洗涤条件是众所周知的，在Sambrook, J.和Russell, D., T. Molecular Cloning: A Laboratory Manual, 第3版, Cold Spring Harbor Laboratory Press, Cold SpringHarbor (2001)中有举例说明。温度和离子强度条件决定杂交的“严格性”。可调整严格性条件以筛选中度相似的分子(例如来自远缘生物的同源序列)至高度相似分子(例如复制来自近缘生物的功能酶的基因)。杂交后洗涤通常决定严格性条件。一组优选的条件采用一系列洗涤，以6X SSC，0.5% SDS在室温下达15分钟开始，然后以2X SSC，0.5% SDS在45℃下30分钟重复，然后以0.2X SSC，0.5% SDS在50℃下30分钟重复两次。更优选的一组条件采用较高温度，其中洗涤与上述条件相同，只是最后在0.2X SSC，0.5% SDS中的两次30分钟洗涤的温度提高到60℃。另一组优选的高严格杂交条件是0.1X SSC，0.1% SDS，65℃,并且用2X SSC，0.1% SDS洗涤，接着0.1X SSC，0.1% SDS，65℃的最终洗涤。
杂交要求两个核酸含有互补序列，虽然取决于杂交的严格性，但碱基间的错配是可能的。用于使核酸杂交的合适的严格性取决于本领域众所周知的变量：核酸的长度和互补的程度。两个核苷酸序列之间的相似性或同源性程度越大，具有这些序列的核酸的杂合体的Tm值越大。核酸杂交的相对稳定性(相当于较高的Tm)按以下顺序下降：RNA:RNA、DNA:RNA、DNA:DNA。对于长度大于100个核苷酸的杂合体，已推导出计算Tm的方程式(Sambrook和Russell，同上)。对于与较短核酸(即寡核苷酸)的杂交，错配的位置变得更重要，并且寡核苷酸的长度决定其特异性(Sambrook和Russell，同上)。一方面，可杂交核酸的长度为至少约10个核苷酸。优选可杂交核酸的最小长度为至少约15个核苷酸，更优选长度为至少约20个核苷酸，甚至更优选长度为至少30个核苷酸，甚至更优选长度为至少300个核苷酸，最优选长度为至少800个核苷酸。此外，技术人员应认识到，可根据例如探针的长度等因素按需调节温度和洗涤溶液盐浓度。
本文所用术语“百分比同一性”是两个或更多个多肽序列或两个或更多个多核苷酸序列之间的关系，通过比较序列来确定。本领域中，“同一性”亦指多肽或多核苷酸序列之间序列关联性的程度，视情况，由这类序列串间的匹配确定。“同一性”和“相似性”可容易地通过已知方法计算，包括但不限于描述于以下文献的方法：Computational Molecular Biology (Lesk, A. M.编辑) Oxford University Press, NY (1988)；Biocomputing: Informatics and Genome Projects (Smith, D. W.编辑) Academic Press, NY (1993)；Computer Analysis of Sequence Data, Part I (Griffin, A. M.和Griffin, H. G.编辑) Humana Press, NJ (1994)；Sequence Analysis in Molecular Biology (vonHeinje, G.编辑) Academic Press (1987)；以及Sequence Analysis Primer (Gribskov,M. and Devereux, J.编辑) Stockton Press, NY (1991)。在可公开获取的计算机程序中编入有确定同一性和相似性的方法。可应用LASERGENE生物信息学计算套件的Megalign程序(DNASTAR Inc.，Madison，WI)、Vector NTI 7.0版的AlignX程序(Informax，Inc.，Bethesda，MD)或EMBOSS公开软件套件(EMBL-EBI；Rice等，Trends in Genetics 16，(6):276-277 (2000))进行序列比对和百分比同一性计算。可应用通过欧洲生物信息学研究院(European Bioinformatics Institute)获自欧洲分子生物实验室(European MolecularBiology Laboratory)的比对的Clustal方法(例如CLUSTALW；例如1.83版)，以默认参数进行序列多重比对(Higgins和Sharp, CABIOS, 5:151-153 (1989)；Higgins等, Nucleic Acids Res. 22:4673-4680 (1994)；以及Chenna等, Nucleic Acids Res 31 (13):3497-500 (2003))。CLUSTALW蛋白质比对的合适参数包括GAP延伸罚分=15，GAP延伸=0.2，矩阵=Gonnet (例如Gonnet250)，蛋白质ENDGAP=-1，蛋白质GAPDIST=4，KTUPLE=1。在一个实施方案中，采用具有默认设置的快或慢比对，其中优选慢比对。或者，采用CLUSTALW方法(例如1.83版)的参数可经改进，以亦采用KTUPLE=1，GAP PENALTY=10，GAP延伸=1，矩阵=BLOSUM(例如BLOSUM64)，WINDOW=5和TOP DIAGONALS SAVED=5。
一方面，合适的分离核酸分子编码具有与本文报告的氨基酸序列有以下同一性的氨基酸序列的多肽：至少约20%、优选至少30%、33%、40%、50%、60%、70%、80%、85%、90%、91%、92%、93%、94%、95%、96%、97%、98%或99%。另一方面，合适的分离核酸分子编码具有与本文报告的氨基酸序列有以下同一性的氨基酸序列的多肽：至少约20%、优选至少30%、33%、40%、50%、60%、70%、80%、85%、90%、91%、92%、93%、94%、95%、96%、97%、98%或99%。合适的核酸分子不仅具有上述同源性，而且还通常编码具有长度为约210-340个氨基酸、约300-约340个氨基酸、优选约310-约330个氨基酸、最优选长度约318-约325氨基酸的多肽，其中各多肽的特征在于具有过水解活性。
靶向过水解酶
本文所用术语“靶向过水解酶”和“具有过水解活性的靶向酶”可指包含与对靶向表面(优选靶向身体表面)具有亲和力的至少一种肽组分融合/偶联的至少一种过水解酶(野生型或其变体)的融合蛋白。靶向过水解酶内的过水解酶可以是具有过水解活性的任何CE-7碳水化合物酯酶。CE-7过水解酶可通过与参比序列SEQ ID NO: 1对准(align with)的CE-7签名基序的存在来鉴定，所述签名基序包含：
i) 对应于SEQ ID NO: 1的118-120位的位置上的RGQ基序；
ii) 对应于SEQ ID NO:1的186-190位的位置上的GXSQG基序；和
iii) 对应于SEQ ID NO:1的303-304位的位置上的HE基序。
如本文所用，核酸分子当第一分子的单链在合适的温度和溶液条件下可与其它分子退火时，该核酸分子与另一核酸分子(例如cDNA、基因组DNA或RNA)是“可杂交的”。在一个实施方案中，过水解酶可以是具有与本文报告的氨基酸序列的任一个(即SEQ ID NO: 1和4-28)有以下同一性的氨基酸序列的那些过水解酶：至少约20%、优选至少30%、33%、40%、50%、60%、70%、80%、85%、90%、91%、92%、93%、94%、95%、96%、97%、98%或99%。
在另一个实施方案中，融合蛋白包含具有选自SEQ ID NO: 1和4-28的氨基酸序列的过水解酶。
本文所用术语“肽组分”、“对口腔表面具有亲和力的肽组分”、“口腔结合域”和“OCBD”指不是过水解酶的部分、包含至少一个通过肽键连接的两个或更多个氨基酸的聚合物的融合蛋白的组分；其中该组分对靶标口腔表面具有亲和力。在一个优选的方面，OCBD对牙釉质具有亲和力。
在一个实施方案中，对身体表面具有亲和力的肽组分可以是抗体、Fab抗体片段、单链可变片段(scFv)抗体、骆驼抗体(Muyldermans, S., Rev. Mol. Biotechnol. (2001)74:277-302)、非抗体支架展示蛋白质(non-antibody scaffold display protein) (对于各种支架辅助方法的综述：Hosse等, Prot. Sci. (2006) 15(1): 14-27和Binz, H.等(2005) Nature Biotechnology 23, 1257-1268)或没有免疫球蛋白折叠的单链多肽。另一方面，对口腔组织/表面(例如牙釉质)具有亲和力的肽组分是没有免疫球蛋白折叠的单链肽。
对口腔表面具有亲和力的肽组分可通过任选的肽接头与过水解酶分隔开。某些肽接头/间隔基长度为1-100或1-50个氨基酸。在一些实施方案中，肽间隔基长度为约1-约25、3-约40或3-约30个氨基酸。在其它实施方案中，为长度约5-约20个氨基酸的间隔基。可使用多个肽接头。在一个实施方案中，存在至少一个肽接头，并且可重复多达10次。
在一个实施方案中，融合肽包含至少一种选自SEQ ID NO: 178-197的口腔表面结合肽。
对口腔表面具有亲和力的肽组分可通过任选的肽接头与CE-7过水解酶分隔开。某些肽接头/间隔基长度为1-100或1-50个氨基酸。在一些实施方案中，肽间隔基长度为约1-约25、3-约40或3-约30个氨基酸。在其它实施方案中，为长度约5-约20个氨基酸的间隔基。可使用多个肽接头。肽接头的实例以SEQ ID NO: 164 – 177提供。
因此，靶向CE-7过水解酶的实例可包括但不限于具有选自与对口腔表面具有亲和力的肽组分偶联的SEQ ID NO: 1和4-28的氨基酸序列的CE-7过水解酶的任一个。在一个优选的实施方案中，靶向过水解酶的实例可包括但不限于具有选自与对口腔表面具有亲和力的一个或多个身体表面结合肽偶联(任选通过肽间隔基)的SEQ ID NO: 1、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24、25、26、27和28的氨基酸序列的CE-7过水解酶的任一个。在一个优选的实施方案中，靶向过水解酶包括具有选自SEQ ID NO: 1和16的氨基酸序列的CE-7过水解酶。
在一个实施方案中，过水解酶是呈具有下列通用结构的融合蛋白形式的CE-7过水解酶：
PAH-[L]y-OCBD或OCBD-[L]y-PAH
其中PAH为具有过水解活性(例如具有CE-7签名基序)的酶，例如SEQ ID NO:1，OCBD为对口腔表面具有亲和力的肽组分，L为任选的接头，y为0-10的整数。在一个实施方案中，接头(L)存在，并且是长度为1-100个氨基酸的肽接头。
例如SEQ ID NO: 2是具有与对口腔组织有亲和力的C端靶向结构域偶联的SEQ IDNO: 1的过水解酶序列的融合蛋白。
用于本发明的产品和方法的过水解酶可呈游离形式、保护形式(例如乙酰化)或盐形式。
在另一个实施方案中，目标表面是作为包装和/或递送至口腔的部分的材料。针对其对使用的一种或多种材料(例如聚合物、塑料和薄膜)的亲和力选择肽组分。靶向CE-7过水解酶融合蛋白设计允许通过将其保持在可移动装置(例如口腔托盘或条)上而由使用者控制释放并除去过水解酶。
结合亲和力
对口腔表面具有亲和力的肽组分包括10-5摩尔(M)以下的对口腔表面的结合亲和力。在某些实施方案中，肽组分是对牙釉质具有10-5摩尔(M)以下结合亲和力的一个或多个口腔表面结合肽和/或结合域。在一些实施方案中，在至少约50 – 500 mM盐的存在下，结合肽或结合域的结合亲和力值可为10-5 M以下。术语“结合亲和力”是指结合肽与其相应底物的相互作用的强度。结合亲和力可以用结合肽的解离常数(“KD”)或“MB50”来定义或测量。
“KD”相当于靶标的结合部位被占据一半时肽的浓度，即具有肽结合的靶标(结合的靶标材料)的浓度等于没有肽结合的靶标的浓度。解离常数越小，肽结合得越牢固。例如，具有纳摩尔(nM)解离常数的肽比具有微摩尔(μM)解离常数的肽更牢固地结合。本发明的某些实施方案可具有10-5以下的KD值。
“MB50”是指产生是在ELISA型结合测定法中获得的最大信号50%的信号的结合肽的浓度。参见例如美国专利申请公布2005/022683的实施例3；通过引用结合到本文中。MB50提供复合物组分的结合相互作用或亲和力的强度的指征。MB50值越低，肽与其相应底物的相互作用越强即“越好”。例如，具有纳摩尔(nM) MB50的肽比具有微摩尔(μM) MB50的肽更牢固地结合。本发明的某些实施方案可具有10-5 M以下的MB50值。
在一些实施方案中，如通过KD或MB50值测量，对口腔表面具有亲和力的肽组分可具有小于或等于约10-5 M、小于或等于约10-6 M、小于或等于约10-7 M、小于或等于约10-8 M、小于或等于约10-9 M或小于或等于约10-10 M的结合亲和力。
在一些实施方案中，如通过KD或MB50值测量，口腔表面结合肽和/或口腔表面-结合域可具有小于或等于约10-5 M、小于或等于约10-6 M、小于或等于约10-7 M、小于或等于约10-8 M、小于或等于约10-9 M或小于或等于约10-10 M的结合亲和力。
本文所用术语“强亲和力”可指KD或MB50值小于或等于约10-5 M、优选小于或等于约10-6 M、更优选小于或等于约10-7 M、更优选小于或等于约10-8 M、小于或等于约10-9 M或最优选小于或等于约10-10 M的结合亲和力。
酶粉
在一些实施方案中，个人护理组合物可使用呈稳定型酶粉形式的酶催化剂。制备并稳定包含酶粉的制剂的方法描述于美国专利申请公布号2010-0086534和2010-0086535。
在一个实施方案中，酶可以是量为以酶粉干重计范围约5重量百分比(wt%)-约75wt%的酶粉。酶粉/喷雾干燥混合物中酶优选的重量百分比范围为约10 wt%-50 wt%，酶粉/喷雾干燥混合物中酶更优选的重量百分比范围为约20 wt%-33 wt%。
在一个实施方案中，酶粉还可包含赋形剂。一方面，赋形剂按以酶粉干重计约95wt%-约25 wt%的量提供。酶粉中赋形剂优选的wt%范围为约90 wt%-50 wt%，酶粉中赋形剂更优选的wt%范围为约80 wt%-67 wt%。
在一个实施方案中，用于制备酶粉的赋形剂可以是寡糖赋形剂。在一个实施方案中，寡糖赋形剂的数均分子量为至少约1250，重量平均分子量为至少约9000。在一些实施方案中，寡糖赋形剂的数均分子量为至少约1700，重量平均分子量为至少约15000。具体的寡糖可包括但不限于麦芽糖糊精、木聚糖、普鲁兰多糖、甘露聚糖、岩藻依聚糖、半乳甘露聚糖、脱乙酰壳多糖、棉子糖、水苏糖、果胶、胰岛素(insulin)、果聚糖、裸麦聚果糖(graminan)、支链淀粉、蔗糖、乳果糖、乳糖、麦芽糖、海藻糖、纤维二糖、黑曲三糖(nigerotriose)、麦芽三糖、松三糖、maltotriulose、棉子糖、蔗果三糖及其混合物。在一个优选的实施方案中，寡糖赋形剂是麦芽糖糊精。基于寡糖的赋形剂还可包括但不限于水溶性非离子纤维素醚，例如羟甲基纤维素和羟丙基甲基纤维素及其混合物。在再一个实施方案中，赋形剂可选自但不限于一种或多种下列化合物：海藻糖、乳糖、蔗糖、甘露糖醇、山梨糖醇、葡萄糖、纤维二糖、α-环糊精、普鲁兰多糖和羧甲基纤维素。
合适的酯底物/酰基供体
合适的羧酸酯底物可包括具有下式的酯：
(a) 一种或多种具有以下结构的酯
[X]mR5
其中
X为式R6C(O)O的酯基；
R6为被羟基或C1-C4烷氧基任选取代的C1-C7直链、支链或环状烃基部分，其中在R6为C2-C7时，R6任选包含一个或多个醚键；
R5为被羟基任选取代的C1-C6直链、支链或环状烃基部分或5元环状杂芳族部分或6元环状芳族或杂芳族部分；其中R5中的每个碳原子各自包含不超过一个羟基或不超过一个酯基或羧酸基，且其中R5任选包含一个或多个醚键；
m为1至R5中的碳原子数的整数，
所述一种或多种酯在25℃下在水中具有至少5 ppm的溶解度；或
(b) 具有以下结构的一种或多种甘油酯
Figure DEST_PATH_IMAGE004
其中R1为被羟基或C1-C4烷氧基任选取代的C1-C7直链或支链烷基，R3和R4各自为H或R1C(O)；或
(c) 下式的一种或多种酯
Figure DEST_PATH_IMAGE005
其中R1为被羟基或C1-C4烷氧基任选取代的C1-C7直链或支链烷基，R2为C1-C10直链或支链烷基、烯基、炔基、芳基、烷基芳基、烷基杂芳基、杂芳基、(CH2CH2O)n或(CH2CH(CH3)-O)nH，且n为1-10；或
(d) 一种或多种乙酰化单糖、乙酰化二糖或乙酰化多糖；或
(e) (a)至(d)的任何组合。
合适的底物还可包括选自酰化单糖、二糖和多糖的一种或多种酰化糖类。在另一个实施方案中，酰化糖类选自乙酰化木聚糖、乙酰化木聚糖的片段、乙酰化木糖(例如木糖四乙酸酯)、乙酰化葡萄糖(例如α-D-葡萄糖五乙酸酯、β-D-葡萄糖五乙酸酯、1-巯基-β-D-葡萄糖-2,3,4,6-四乙酸酯)、β-D-半乳糖五乙酸酯、山梨糖醇六乙酸酯、蔗糖八乙酸酯、β-D-呋喃核糖-1,2,3,5-四乙酸酯、β-D-呋喃核糖-1,2,3,4-四乙酸酯、三-O-乙酰基-D-半乳醛、三-O-乙酰基-D-己烯糖、β-D-呋喃木糖四乙酸酯，β-D-吡喃葡萄糖五乙酸酯、β-D-吡喃葡萄糖-1,2,3,4-四乙酸酯、β-D-吡喃葡萄糖-2,3,4,6-四乙酸酯、2-乙酰氨基-2-脱氧-1,3,4,6-四乙酰基-β-D-吡喃葡萄糖、2-乙酰氨基-2-脱氧-3,4,6-三乙酰基-1-氯(chloride)-α-D-吡喃葡萄糖、β-D-甘露吡喃糖五乙酸酯和乙酰化纤维素。在一个优选的实施方案中，乙酰化糖选自β-D-呋喃核糖-1,2,3,5-四乙酸酯、三-O-乙酰基-D-半乳醛、三-O-乙酰基-D-己烯糖、蔗糖八乙酸酯和乙酰化纤维素。
在另一个实施方案中，其它合适的底物还可包括5-乙酰氧基甲基-2-糠醛、3,4-二乙酰氧基-1-丁烯、4-乙酰氧基苯甲酸、香草醛乙酸酯、丙二醇甲醚乙酸酯、乳酸甲酯、乳酸乙酯、羟乙酸甲酯、羟乙酸乙酯、甲氧基乙酸甲酯、甲氧基乙酸乙酯、3-羟基丁酸甲酯、3-羟基丁酸乙酯和2-乙酰基柠檬酸三乙酯。
在另一个实施方案中，合适的底物选自：一醋精、二醋精、三醋精、单丙酸甘油酯(monopropionin)、二丙酸甘油酯、三丙酸甘油酯、单丁酸甘油酯、二丁酸甘油酯、三丁酸甘油酯、葡萄糖五乙酸酯、木糖四乙酸酯、乙酰化木聚糖、乙酰化木聚糖片段、β-D-呋喃核糖-1,2,3,5-四乙酸酯、三-O-乙酰基-D-半乳醛、三-O-乙酰基-D-己烯糖，1,2-乙二醇、1,2-丙二醇、1,3-丙二醇、1,2-丁二醇、1,3-丁二醇、2,3-丁二醇、1,4-丁二醇、1,2-戊二醇、2,5-戊二醇、1,5-戊二醇、1,6-戊二醇、1,2-己二醇、2,5-己二醇、1,6-己二醇的单酯或二酯，及其混合物。在另一个实施方案中，底物为包含一个或多个酯基的C1-C6多元醇。在一个优选的实施方案中，C1-C6多元醇上的一个或多个羟基被一个或多个乙酰氧基取代(例如1,3-丙二醇二乙酸酯、1,2-丙二醇二乙酸酯、1,4-丁二醇二乙酸酯、1,5-戊二醇二乙酸酯等)。在又一个实施方案中，底物是丙二醇二乙酸酯(PGDA)、乙二醇二乙酸酯(EGDA)或其混合物。
在又一个实施方案中，合适的底物选自一醋精、二醋精、三醋精、单丙酸甘油酯、二丙酸甘油酯、三丙酸甘油酯、单丁酸甘油酯、二丁酸甘油酯和三丁酸甘油酯。再一方面，底物选自二醋精和三醋精。在一个最优选的实施方案中，合适的底物包含三醋精。
羧酸酯以在酶催化过水解时足以产生所需的过氧羧酸浓度的浓度存在。羧酸酯不必完全溶于反应制剂中，但是具有足够的溶解度允许酯被过水解酶催化剂转化为相应的过氧羧酸。羧酸酯在反应制剂中以反应制剂的0.05 wt%-40 wt%的浓度存在，优选为反应制剂的0.1 wt%-20 wt%的浓度，更优选为反应制剂的0.5 wt%-10 wt%的浓度。
过氧源以颗粒提供，且可包括过氧化氢加合物(例如脲-过氧化氢加合物(过氧化氢脲))、过硼酸盐、过碳酸盐和过氧化物盐。反应制剂中过氧化合物的浓度的范围可为0.0033 wt%-约50 wt%，更优选0.033 wt%-约40 wt%，更优选0.1 wt%-约30 wt%。
据报道许多过水解酶催化剂(完整细胞、透化完整细胞和部分纯化的完整细胞提取物)具有过氧化氢酶活性(EC 1.11.1.6)。过氧化氢酶催化过氧化氢转化成氧和水。一方面，过水解催化剂没有过氧化氢酶活性。另一方面，可将过氧化氢酶抑制剂加入反应制剂中。本领域技术人员可根据需要调节过氧化氢酶抑制剂的浓度。过氧化氢酶抑制剂的浓度范围通常为0.1 mM-约1 M、优选约1 mM-约50 mM、更优选约1 mM-约20 mM。
在另一个实施方案中，酶催化剂没有显著的过氧化氢酶活性或可被工程改造以降低或消除过氧化氢酶活性。可通过采用众所周知的技术，包括但不限于转座子诱变、RNA反义表达、定向诱变和随机诱变，破坏负责过氧化氢酶活性的基因的表达，来下调或消除宿主细胞中的过氧化氢酶活性。
在开始过水解反应的10分钟内，优选在5分钟内，通过至少一种羧酸酯过水解所产生的过氧羧酸(例如过乙酸)的浓度为至少约0.1 ppm、优选至少0.5 ppm、1 ppm、5 ppm、10ppm、20 ppm、100 ppm、200 ppm、300 ppm、500 ppm、700 ppm、1000 ppm、2000 ppm、5000 ppm或10,000 ppm的过酸。显然本领域技术人员可调节反应组分以达到所需的过酸浓度。
一方面，产生所需的过酸浓度所需要的反应时间不大于约2小时，优选不大于约30分钟，更优选不大于约10分钟，最优选在约5分钟以下。
测定过氧羧酸和过氧化氢的浓度的HPLC测定方法。
各种分析方法可用来分析反应物和产品，包括但不限于滴定、高效液相色谱法(HPLC)、气相色谱法(GC)、质谱法(MS)、毛细管电泳(CE)、U. Pinkernell等(Anal. Chem.,69(17):3623-3627 (1997))描述的分析方法和2,2’-连氮基-双(3-乙基苯并噻唑啉)-6-磺酸酯(ABTS)测定法(U. Pinkernell等，Analyst，122：567-571 (1997)和Dinu等，Adv. Funct. Mater., 20: 392-398 (2010))，如本发明实施例中所述。
在一个实施方案中，本发明提供用于口腔护理产品的套装，其包含多个室，并被设计成将成分单独和不反应地保持在各室中直到使用时间点。例如，本发明提供化学稳定的结构套装设计，其允许酶催化的牙齿增白产品在成分彼此暴露并混合后在毫秒内达到稳态前动力学。通过开口装置，例如通过带有可移动盖子或塞子或当消费者折断容器的优先划痕的部分时变得起作用时的喷嘴，分配容器的内容物，允许通过有形的喷嘴清洁且方便地分配产品。
各室具有存贮例如0.1 – 30克成分的容量。口腔护理产品是牙齿增白产品，提供从所有室中递送的产品的总量为例如1.0-5.0克、例如1-2克以提供预期益处。各室的容量被设计成容纳比重为例如1.0-1.1、优选比重范围为1.02-1.05的成分。
在一个实施方案中，套装采用厚度为50微米-500微米、优选300微米厚的至少两种挠性薄膜的加热成型工艺来生产。两种薄膜可以是不透明、半透明或透明的，并且当在加热成型工艺中装配时可为任何组合。两种材料均提供水汽屏障特征，例如在3年期限内水分丢失小于3%，例如在相同期限内水分丢失小于1%。该薄膜还提供气味屏障。味道丢失可通过气相色谱法和通过感官评价确定。
薄膜对本文包含的材料有化学抗性。例如，在一个实施方案，它们耐得住0.1%-10%过氧化氢溶液(按重量计算)，例如高达0.3%过氧化氢溶液(按重量计算)。
在一个实施方案中，两种挠性材料之一是聚合物层压材料，且选择层压材料的内层与第一挠性材料结合，但当向具有易碎密封片的室手工施加压力时，内层将分层。折断密封片所需要的力用手施加，并且可在2英寸-lbf和5英寸-lbf之间变化。
在隔室间的易碎密封片破裂后，各室中的成分将彼此密切接触。允许消费者将各个成分混合一段时间以超过稳态前动力学速率或爆发期(burst phase)。稳态前动力学或爆发期的时间可以毫秒计。这为酶-底物中间体的形成和消耗提供了足够的时间，直到达到其稳态浓度。在达到稳态后，消费者可破裂多室容器的优先划痕部分，并将混合物分配在牙托盘上。将托盘放在牙齿上达15分钟-45分钟的一段时间，并提供有效的增白益处。
本发明的示例性实施方案因此包括例如套装、口腔护理组合物和牙齿增白方法，例如：
1. 套装1，一种包含经配置形成至少两个密封室的可变形材料、具有第一室、第二室和任选其它室的套装，所述各室被一个或多个易碎或易撕裂的屏障分隔开，
其中
第一室含有包含具有过水解活性的酶的低粘度液体溶液，所述酶具有与参比序列SEQ ID NO: 1对准的碳水化合物酯酶家族7 (CE-7)签名基序，所述签名基序包含：
i) 对应于SEQ ID NO: 1的118-120位的位置上的RGQ基序；
ii) 对应于SEQ ID NO:1的186-190位的位置上的GXSQG基序；和
iii) 对应于SEQ ID NO:1的303-304位的位置上的HE基序；和
第二室包含至少一种酰基供体底物，所述底物选自：
i) 具有以下结构的酯
[X]mR5
其中X=式R6C(O)O的酯基
R6=被羟基或C1-C4烷氧基任选取代的C1-C7直链、支链或环状烃基部分，其中在R6为C2-C7时，R6任选包含一个或多个醚键；
R5=被羟基任选取代的C1-C6直链、支链或环状烃基部分或5元环状杂芳族部分或6元环状芳族或杂芳族部分；其中R5中的每个碳原子各自包含不超过一个羟基或不超过一个酯基或羧酸基；其中R5任选包含一个或多个醚键；
M为1至R5中的碳原子数的整数；和
其中所述酯在25℃下在水中具有至少5 ppm的溶解度；
ii) 具有以下结构的甘油酯
Figure DEST_PATH_IMAGE006
其中R1=被羟基或C1-C4烷氧基任选取代的C1-C7直链或支链烷基，且R3和R4独立地为H或R1C(O)；
iii) 下式的一种或多种酯
Figure DEST_PATH_IMAGE007
其中R1为被羟基或C1-C4烷氧基任选取代的C1-C7直链或支链烷基、R2为C1-C10直链或支链烷基、烯基、炔基、芳基、烷基芳基、烷基杂芳基、杂芳基、(CH2CH2O)n或(CH2CH(CH3)-O)nH，且n为1-10；和
iv) 选自乙酰化单糖、乙酰化二糖和乙酰化多糖的乙酰化糖类；和
其中第二室或任选的其它室含有过氧化物源，
使得当例如挤压第一室后室间的一个或多个屏障破裂时，低粘度液体溶液与过氧化物源和酰基供体底物混合，且具有过水解活性的酶催化由过氧化物源释放的过氧化物和酰基供体底物之间的反应形成过酸；和
套装具有开口装置例如划痕区、盖子或塞子，允许打开套装以提供分配混合物的出口。
1.1 套装1，其中具有过水解活性的酶包含选自以下的氨基酸序列：
a) SEQ ID NO: 1；和
b) 与SEQ ID NO: 1具有至少80%氨基酸序列同一性的氨基酸序列
套装1或1.1，其中具有过水解活性的酶还包含与酶的N端或C端融合的结合域，所述结合域对口腔组织或对牙齿增白条具有亲和力。
1.2. 前述套装的任一个，其中对口腔组织具有亲和力的结合域包含选自SEQ IDNO: 178-197的氨基酸序列。
1.3. 前述套装的任一个，其中具有过水解活性的酶对口腔组织具有亲和力，并且包含选自SEQ ID NO: 2的氨基酸序列和与SEQ ID NO: 2具有至少80%氨基酸序列同一性的氨基酸序列。
1.4. 前述套装的任一个，其中可变形材料是塑料或铝。
1.5前述套装的任一个，其中低粘度液体溶液具有足够低以确保与第二室的内容物混合的粘度，例如低于5,000 cps，例如低于500 cps。
1.6. 前述套装的任一个，其中低粘度液体溶液包含缓冲剂。
1.7. 前述套装的任一个，其中酰基供体底物选自(i)一种或多种C2-18羧酸，例如C2-6羧酸(例如乙酸)，包括被羟基和/或C1-4烷氧基任选取代的低级直链或支链烷基羧酸；(ii)其一种或多种可水解和可接受的酯(例如甘油单酯、甘油二酯和甘油三酯和酰化糖类)；和(iii)其混合物。
1.8. 前述套装的任一个，其中酰基供体底物选自1,2,3-三乙酰氧基丙烷(本文有时称为三醋精或丙三醇三乙酸酯)和酰化糖类，例如乙酰化糖类。
1.9.前述套装的任一个，其包含酰基供体底物，所述底物包含在25℃下在水中具有至少5 ppm的溶解度的酯化合物。
1.10. 前述套装的任一个，其中过氧化物源选自固体过氧化物和固体过氧化物供体及其混合物，例如选自过氧化物盐或复合物(例如过氧磷酸盐、过氧碳酸盐、过硼酸盐、过氧硅酸盐或过硫酸盐；例如过氧磷酸钙、过硼酸钠、过碳酸钠、过氧磷酸钠和过硫酸钾)；次氯酸盐；过氧化脲；过氧化氢聚合物复合物例如过氧化氢-聚乙烯吡咯烷酮聚合物复合物；金属过氧化物例如过氧化锌和过氧化钙；例如选自以下的固体过氧化物：过氧化脲、聚乙烯吡咯烷酮-过氧化氢复合物、过碳酸钠、过硼酸钠和金属过氧化物，例如过氧化锌和过氧化钙。
1.11. 前述套装，其中过氧化物源是过氧化脲。
1.12. 前述套装，其中过氧化物源包含过氧化氢-聚乙烯吡咯烷酮复合物。
1.13. 前述套装的任一个，其中各室的成分以在混合时提供量和浓度有效增白牙齿的漂白剂的量存在。
1.14. 前述套装的任一个，其中第二室含有呈粉末形式的胶凝剂。
1.15. 前述套装，其中胶凝剂选自卡波姆胶凝剂(例如Carbopol 971P)、多糖树胶例如黄原胶、改性食品淀粉、基于动物或鱼的明胶和二氧化硅。
1.16. 前述套装，其中胶凝剂是卡波姆胶凝剂。
1.17. 前述套装的任一个，其中第二室含有相对量为在与第一室的内容物混合时提供100,000-150,000 cps、例如约125,000 cps的粘度的呈粉末形式的胶凝剂，例如其中胶凝剂以占第一室和第二室的内容物的最终混合物重量的5%-50%的量存在。
1.18. 前述套装的任一个，其中第一室含有包含具有过水解活性的酶和缓冲剂的低粘度水溶液，第二室含有均为粉末形式的胶凝剂、过氧化物源和含乙酰基的化合物，使得当易碎屏障破裂且两室的内容物被允许混合时，过氧化物和含乙酰基化合物可发生由具有过水解酶活性的蛋白质催化的反应，以在由液体和胶凝剂形成的可挤出凝胶中形成过乙酸，然后可使用例如托盘或条，将所述可挤出凝胶挤出并涂覆于牙齿上持续足够的时间(例如10-30分钟)，以漂白牙齿。
1.19. 前述套装的任一个，其还包含涂覆装置例如牙托盘或条，用于将第一室和第二室的内容物的混合物涂覆在牙齿上。
1.20. 前述套装，其中当分配混合物时，将第二室的开口与托盘直接连接，使得混合物被挤进托盘中。
2. 组合物2，为多部分口腔护理组合物，其包含在贮存期间与第二部分物理上分隔并且在临用前(例如用前10分钟内)与第二部分混合的第一部分，其中第一部分包含前述套装任一个所述的具有过水解活性的酶，第二部分包含过氧化物源和选自羧酸和酰基化合物的羧基供体，其中过氧化物源和羧基供体(例如前述套装的任一个所述的过氧化物源和羧基供体)在过水解酶的存在下发生反应形成过酸，
2.1. 前述组合物，其中羧基供体选自C2-18羧酸(例如乙酸)及其可水解和可接受的酯(例如甘油单酯、甘油二酯和甘油三酯)及其混合物。
2.2. 前述组合物，其中羧基供体是1,2,3-三乙酰氧基丙烷(本文有时称为三醋精或丙三醇三乙酸酯)。
2.3. 前述组合物的任一种，其中过氧化物源是选自以下的固体过氧化物：过氧化脲、聚乙烯吡咯烷酮-过氧化氢复合物、过碳酸钠、过硼酸钠和金属过氧化物，例如过氧化锌和过氧化钙。
2.4. 前述组合物的任一种，其中过氧化物源是过氧化脲。
2.5. 前述组合物的任一种，其中过氧化物源包含过氧化氢-聚乙烯吡咯烷酮复合物。
2.6. 包装在本文上述套装(例如套装1及其后述套装)中的前述组合物的任一种。
3. 一种增白牙齿的方法(方法3)，所述方法包括通过将上述两部分口腔护理组合物的两部分混合以激活所述组合物，并使用例如涂覆器(例如牙托盘或条)，将有效量的由此获得的混合物涂覆在牙齿上达足够的时间，例如至少10分钟，例如10-30分钟，以增白牙齿。
已知过氧羧酸(“过酸”)为有效的抗微生物剂和漂白剂。Viscio, D.的美国专利5,302,375公开了用于增白的包含溶于溶媒中的过乙酸的口腔组合物，其中通过将水、乙酰水杨酸和水溶性碱金属过碳酸盐混合，在溶媒内原位产生过乙酸。Church等人的美国专利5,279,816公开了使着色或脱色的牙齿变白的包含过乙酸的组合物的用途。Montgomery，R.的美国专利6,221,341和7,189,385公开了适用于牙齿增白方法的过氧酸牙齿增白组合物。更具体地讲，可通过将过氧化氢前体、甘油乙酸酯和水混合以经化学过水解产生过乙酸，来产生过乙酸组合物。
这些参考文献没有披露酶促过水解。Concar等人的美国专利申请公布号2009-0311198公开了包含具有过水解活性的酶的耻垢分枝杆菌(M. smegmatis)的口腔组合物以漂白牙齿。
许多水解酶和酯酶(例如脂肪酶、丝氨酸水解酶和碳水化合物酯酶)催化过水解，即由羧酸和过氧化氢可逆地形成过酸。过水解酶、酯酶和脂肪酶一般含有由丝氨酸(Ser)、谷氨酸(Glu)或天冬氨酸(Asp)和组氨酸(His)组成的催化三联体。许多过水解酶(例如不含金属的卤过氧化物酶(haloperoxidase))含有Ser-His-Asp催化三联体，并催化由过氧化氢和羧酸可逆地形成过酸。虽不受理论束缚，但是认为过水解按酯酶样机制发生，其中羧酸与活性部位丝氨酸反应形成酰基酶中间体，其随后与过氧化氢反应形成过酸。
本领域已描述了多种过水解酶。Wieland等人的美国专利7,510,859公开了包括在身体护理产品中的具有过水解活性的特殊变异枯草杆菌蛋白酶Carlsberg蛋白酶。没有披露特殊变异蛋白酶以外的过水解酶，也没有表明酶促产生过酸作为个人护理增益剂的任何有效实例。DiCosimo等人的美国专利申请公布号2008-0176783 A1、2008-0176299 A1、2009-0005590 A1和2010-0041752 A1公开了结构上归类为碳水化合物酯酶的CE-7家族的成员的酶(即头孢菌素C脱乙酰酶[CAH]和乙酰木聚糖酯酶[AXE])，其特征在于将羧酸酯底物(在合适的过氧源例如过氧化氢存在下)转化成浓度足以用作消毒剂和/或漂白剂的过氧羧酸的显著过水解活性。已证实一旦将反应组分混合，碳水化合物酯酶的一些CE-7家族成员具有足以在1分钟内从醇、二醇和甘油的乙酰基酯产生4000 – 5000 ppm过乙酸及在5分钟和30分钟内产生高达9000 ppm过乙酸的过水解活性(DiCosimo等，美国2009-0005590A1)。美国专利申请公布号2010-0087529 A1描述了过水解活性得到改进的变异CE-7酶。
在一个实施方案中，本发明使用含有具有过水解活性的多个碳水化合物酯酶家族7成员的催化域的过水解酶(“CE-7过水解酶”)。虽然CE-7过水解酶具有优异的过水解活性，但在前述临时申请前未公开过其在美容个人护理产品中的用途。
本发明的酰基供体选自(i)被羟基和/或C1-4烷氧基任选取代的一种或多种C2-18羧酸酯，例如C2-6羧酸酯，包括低级直链或支链烷基羧酸，和(ii)其混合物。例如，酰基供体包括1,2,3-三乙酰氧基丙烷(本文有时称为三醋精或丙三醇三乙酸酯)和酰化糖类，例如乙酰化糖类。在一个具体实施方案中，用于该用途的酯可为例如在25℃下在水中具有至少5 ppm的溶解度的酯。
酰基供体或其它材料可任选被胶囊化。有多种本领域已知的天然和合成的胶囊化选择。改性淀粉和阿拉伯树胶是特别适当的，因为它们是食品级的，相对便宜，快速溶解，并且可吸收相当高水平的液体油。需要考虑对最终粘度的任何影响。
如上所述，本发明可包含胶凝剂，例如卡波姆胶凝剂(例如Carbopol 971P)、多糖树胶例如黄原胶、改性食品淀粉、基于动物或鱼的明胶和二氧化硅。与牙齿增白剂一起使用的粘性凝胶制剂是本领域已知的，如例如美国专利7,862,801、5,746,598、6,730,316、7,128,899中所述。胶凝剂可用于使增白溶液增稠至不会从牙托盘流出或从牙齿流到软组织区的程度。这使得漂白剂保持与牙接触达一段长的时间，并保护软组织。牙托盘和粘性漂白剂的使用允许低浓度漂白剂，以对患者的最低风险在1-2周时间内有效地使个体牙齿增白。应选择并调整该用途的胶凝剂以提供涂覆时100,000-150,000 cps、例如约125,000 cps的粘度。
在一个具体实施方案中，上文所述套装或多部分组合物包含卡波姆胶凝剂，例如改性聚丙烯酸亲水聚合物，例如Lubrizol生产的CARBOPOL®。卡波姆能够按上述小至5%(重量)的浓度形成粘性凝胶。
用于本文所述制剂的所有成分均是口用可接受的。所谓“口用可接受的”作为术语在本文使用时意指如所述以在用于口腔时不会使制剂不安全的量和形式存在于制剂中的成分。
在一些实施方案中，具有过水解活性的酶包含选自以下的氨基酸序列：a) SEQ IDNO: 1；和b) 与SEQ ID NO: 1具有至少80%氨基酸序列同一性的氨基酸序列。
在一些实施方案中，具有过水解活性的酶还包含与酶的N端或C端融合的结合域，所述结合域对口腔组织具有亲和力。
在一些实施方案中，具有过水解活性的酶对口腔组织具有亲和力，并且包含选自以下的氨基酸序列：a) SEQ ID NO: 2，和b)与SEQ ID NO: 2具有至少80%氨基酸序列同一性的氨基酸序列。
在一些实施方案中，固定化酶吸附在不溶性材料上、截留在不溶性珠粒中、通过化学反应与不溶性材料共价键合、通过对不溶性材料具有亲和力的肽的结合域连接或包埋在不溶性基质中。
一些实施方案提供增白牙齿或治疗龈炎、牙菌斑或口臭的方法，所述方法包括按照前述要求保护的方法制备包含增白剂的液体，并将液体给予口腔，例如通过用该液体漱口达15秒钟-1分钟的时间，然后吐出该液体。
在一些实施方案中，产品递送漱口剂中的漂白剂，其中漂白剂是通过过氧化氢和三醋精的酶催化反应所产生的过酸。在一些实施方案中，两种组合物(一种包含过氧化氢，另一种包含三醋精)贮存在漱口瓶(第一区室)中。一些实施方案包括(在该瓶顶部)第二区室，其例如使用插入式或螺旋式接头连接。在一些实施方案中，第二区室是例如穿流药筒(flow through cartridge)，其含有固定在所携带材料(例如羟磷灰石或纤维素颗粒)表面的具有过水解活性的酶。在一些实施方案中，第二区室用作漱口剂的活化组分。
在一些实施方案中，过氧化氢和三醋精与具有过水解活性的酶分隔开。在一些实施方案中，在使用期间，混合物流过该药筒，与表面上具有过水解活性的酶接触，并且反应经催化以快速产生过酸。在一些实施方案中，在使用后，将混合物再次与酶分隔开。
如全文所用，范围用作用于描述在该范围内的每个和所有值的简写。该范围内的任何值可选择为该范围的末端。另外，本文引用的所有参考文献均通过引用以其整体结合到本文中。在本公开内容的定义与所引用的参考文献的定义有冲突的情况下，以本公开内容为准。
除非另有说明，否则本文或说明书的其它部分所表达的所有百分比和量应理解为是指重量百分比。量根据材料的有效重量给出。
实施例
实施例1
在两室套装中，含有0.04 mg过水解酶的1.0 mL pH 7磷酸盐缓冲液与多组分粉料分别贮存。多组分粉料见表1A、1B和1C，并包含胶囊化三醋精与香料、颗粒状过氧化脲和卡波姆胶凝剂。在该实施例中，充分混合的粉料的比例1A:1B:1C为92.3:1.7:6。用水不渗透热封屏障分隔两室，所述屏障没有套装周围的外层密封牢固(参见例如图1)。为准备使用，消费者按压缓冲剂/酶室，这破坏易碎内密封，将缓冲剂/酶推入粉料室。粉料与液体快速混合，溶解过氧化物源、淀粉与所吸附的三醋精与香料，且更缓慢地使胶凝剂水合。在混合这些组分几秒钟后，凝胶有效地形成，并准备就绪待加入托盘中。将约0.5克新形成的凝胶加入上和下递送装置，得到4.3 mg过氧化脲(相当于1.5 mg过氧化氢)、10 mg三醋精和0.01mg水解酶的剂量。
打开套装的孔，使用者通过预划痕开口(参见图1)，可将凝胶加到托盘上，然后戴上托盘20-30分钟。或者，可将凝胶加在挠性条例如无孔挠性聚乙烯或缓慢溶解薄膜上。
表1A –胶囊化三醋精
成分 重量%
淀粉(CAPSUL®，National Starch) 94.6
三醋精 4.3
香料 1.1
共计 100
表1B –过氧化物
成分 重量%
过氧化脲颗粒，5-10微米 100
表1C –固体胶凝剂
Figure DEST_PATH_IMAGE008
实施例2
将示例性过水解酶固定在固体可渗透基质上。将基质装载到注射器中，推动包含过氧化氢和三醋精的溶液通过基质以产生并分配过乙酸(PAA)。
原型酶基质如下制备：将0.1 g羟磷灰石粉料与1500微升在10 mM磷酸盐缓冲液pH7.2中的5微摩尔浓度的具有过水解区和羟磷灰石结合域的酶于37℃温育1小时。粉料然后用1 ml 10 mM磷酸盐缓冲液洗涤3次，每次离心，吸出液体，重新悬浮于缓冲液中，并重复。然后将粉料重新悬浮于500微升10 mM磷酸盐缓冲液中，装载到具有25 m注射器过滤嘴(5微米膜)的3 ml注射器中，过量液体通过滤器分配。
包含100 mM磷酸盐缓冲剂、100 mM三醋精和100 mM过氧化氢的500微升反应缓冲液装载到注射器中，通过滤器分配并收集。收集90微升的产物，然后用40微升1.3M H3PO4终止反应。然后将所得混合物在磷酸盐缓冲液中1:10稀释，加到检测试剂中，温育10分钟，在A405 nm处读数。测量所产生的PAA的比例。然后重复没有酶的方法，作为对照。
与没有过水解酶时的32 ppm相比，该方法产生约900 ppm的PAA。使反应物与固定化酶接触小于60秒钟：
表2A
样品 PAA (ppm) 标准差
酶 903.818 122.922
无酶 32.438 2.414
重复实验，3次有酶，3次无酶；允许与酶接触不超过15秒钟。有酶时以约300-350ppm、无酶时以约65 ppm的水平始终产生PAA。结果见下表2B。
表2B
样品 PAA (ppm) 标准差
酶1 363.380 74.462
酶2 356.309 43.188
酶3 308.960 55.096
无酶1 66.066 2.663
无酶2 63.299 0.533
无酶3 65.759 0.533
使用较大(10 ml)注射器获得相似结果：
表2C
样品 PAA (ppm) 标准差
酶 333.864 65.987
无酶 62.223 1.399
因此，该反应在固定化酶存在下可重现、快速和有效地进行，提供是杀死细菌所需水平多倍的PAA水平，并且可充分使牙齿增白。
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<110> 高露洁－棕榄公司
纳幕尔杜邦公司
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<220>
<221> CDS
<222> (1)..(960)
<400> 3
atg caa cta ttc gat ctg ccg ctc gac caa ttg caa aca tat aag cct 48
Met Gln Leu Phe Asp Leu Pro Leu Asp Gln Leu Gln Thr Tyr Lys Pro
1 5 10 15
gaa aaa aca gca ccg aaa gat ttt tct gag ttt tgg aaa ttg tct ttg 96
Glu Lys Thr Ala Pro Lys Asp Phe Ser Glu Phe Trp Lys Leu Ser Leu
20 25 30
gag gaa ctt gca aaa gtc caa gca gaa cct gat tta cag ccg gtt gac 144
Glu Glu Leu Ala Lys Val Gln Ala Glu Pro Asp Leu Gln Pro Val Asp
35 40 45
tat cct gct gac gga gta aaa gtg tac cgt ctc aca tat aaa agc ttc 192
Tyr Pro Ala Asp Gly Val Lys Val Tyr Arg Leu Thr Tyr Lys Ser Phe
50 55 60
gga aac gcc cgc att acc gga tgg tac gcg gtg cct gac aag caa ggc 240
Gly Asn Ala Arg Ile Thr Gly Trp Tyr Ala Val Pro Asp Lys Gln Gly
65 70 75 80
ccg cat ccg gcg atc gtg aaa tat cat ggc tac aat gca agc tat gat 288
Pro His Pro Ala Ile Val Lys Tyr His Gly Tyr Asn Ala Ser Tyr Asp
85 90 95
ggt gag att cat gaa atg gta aac tgg gca ctc cat ggc tac gcc gca 336
Gly Glu Ile His Glu Met Val Asn Trp Ala Leu His Gly Tyr Ala Ala
100 105 110
ttc ggc atg ctt gtc cgc ggc cag cag agc agc gag gat acg agt att 384
Phe Gly Met Leu Val Arg Gly Gln Gln Ser Ser Glu Asp Thr Ser Ile
115 120 125
tca ctg cac ggt cac gct ttg ggc tgg atg acg aaa gga att ctt gat 432
Ser Leu His Gly His Ala Leu Gly Trp Met Thr Lys Gly Ile Leu Asp
130 135 140
aaa gat aca tac tat tac cgc ggt gtt tat ttg gac gcc gtc cgc gcg 480
Lys Asp Thr Tyr Tyr Tyr Arg Gly Val Tyr Leu Asp Ala Val Arg Ala
145 150 155 160
ctt gag gtc atc agc agc ttc gac gag gtt gac gaa aca agg atc ggt 528
Leu Glu Val Ile Ser Ser Phe Asp Glu Val Asp Glu Thr Arg Ile Gly
165 170 175
gtg aca gga gga agc caa ggc gga ggt tta acc att gcc gca gca gcg 576
Val Thr Gly Gly Ser Gln Gly Gly Gly Leu Thr Ile Ala Ala Ala Ala
180 185 190
ctg tca gac att cca aaa gcc gcg gtt gcc gat tat cct tat tta agc 624
Leu Ser Asp Ile Pro Lys Ala Ala Val Ala Asp Tyr Pro Tyr Leu Ser
195 200 205
aac ttc gaa cgg gcc att gat gtg gcg ctt gaa cag ccg tac ctt gaa 672
Asn Phe Glu Arg Ala Ile Asp Val Ala Leu Glu Gln Pro Tyr Leu Glu
210 215 220
atc aat tcc ttc ttc aga aga aat ggc agc ccg gaa aca gaa gtg cag 720
Ile Asn Ser Phe Phe Arg Arg Asn Gly Ser Pro Glu Thr Glu Val Gln
225 230 235 240
gcg atg aag aca ctt tca tat ttc gat att atg aat ctc gct gac cga 768
Ala Met Lys Thr Leu Ser Tyr Phe Asp Ile Met Asn Leu Ala Asp Arg
245 250 255
gtg aag gtg cct gtc ctg atg tca atc ggc ctg att gac aag gtc acg 816
Val Lys Val Pro Val Leu Met Ser Ile Gly Leu Ile Asp Lys Val Thr
260 265 270
ccg ccg tcc acc gtg ttt gcc gcc tac aat cat ttg gaa aca gag aaa 864
Pro Pro Ser Thr Val Phe Ala Ala Tyr Asn His Leu Glu Thr Glu Lys
275 280 285
gag ctg aag gtg tac cgc tac ttc gga cat gag tat atc cct gct ttt 912
Glu Leu Lys Val Tyr Arg Tyr Phe Gly His Glu Tyr Ile Pro Ala Phe
290 295 300
caa acg gaa aaa ctt gct ttc ttt aag cag cat ctt aaa ggc tga taa 960
Gln Thr Glu Lys Leu Ala Phe Phe Lys Gln His Leu Lys Gly
305 310 315
<210> 4
<211> 318
<212> PRT
<213> 枯草芽孢杆菌
<400> 4
Met Gln Leu Phe Asp Leu Pro Leu Asp Gln Leu Gln Thr Tyr Lys Pro
1 5 10 15
Glu Lys Thr Ala Pro Lys Asp Phe Ser Glu Phe Trp Lys Leu Ser Leu
20 25 30
Glu Glu Leu Ala Lys Val Gln Ala Glu Pro Asp Leu Gln Pro Val Asp
35 40 45
Tyr Pro Ala Asp Gly Val Lys Val Tyr Arg Leu Thr Tyr Lys Ser Phe
50 55 60
Gly Asn Ala Arg Ile Thr Gly Trp Tyr Ala Val Pro Asp Lys Gln Gly
65 70 75 80
Pro His Pro Ala Ile Val Lys Tyr His Gly Tyr Asn Ala Ser Tyr Asp
85 90 95
Gly Glu Ile His Glu Met Val Asn Trp Ala Leu His Gly Tyr Ala Ala
100 105 110
Phe Gly Met Leu Val Arg Gly Gln Gln Ser Ser Glu Asp Thr Ser Ile
115 120 125
Ser Leu His Gly His Ala Leu Gly Trp Met Thr Lys Gly Ile Leu Asp
130 135 140
Lys Asp Thr Tyr Tyr Tyr Arg Gly Val Tyr Leu Asp Ala Val Arg Ala
145 150 155 160
Leu Glu Val Ile Ser Ser Phe Asp Glu Val Asp Glu Thr Arg Ile Gly
165 170 175
Val Thr Gly Gly Ser Gln Gly Gly Gly Leu Thr Ile Ala Ala Ala Ala
180 185 190
Leu Ser Asp Ile Pro Lys Ala Ala Val Ala Asp Tyr Pro Tyr Leu Ser
195 200 205
Asn Phe Glu Arg Ala Ile Asp Val Ala Leu Glu Gln Pro Tyr Leu Glu
210 215 220
Ile Asn Ser Phe Phe Arg Arg Asn Gly Ser Pro Glu Thr Glu Val Gln
225 230 235 240
Ala Met Lys Thr Leu Ser Tyr Phe Asp Ile Met Asn Leu Ala Asp Arg
245 250 255
Val Lys Val Pro Val Leu Met Ser Ile Gly Leu Ile Asp Lys Val Thr
260 265 270
Pro Pro Ser Thr Val Phe Ala Ala Tyr Asn His Leu Glu Thr Glu Lys
275 280 285
Glu Leu Lys Val Tyr Arg Tyr Phe Gly His Glu Tyr Ile Pro Ala Phe
290 295 300
Gln Thr Glu Lys Leu Ala Phe Phe Lys Gln His Leu Lys Gly
305 310 315
<210> 5
<211> 318
<212> PRT
<213> 枯草芽孢杆菌
<400> 5
Met Gln Leu Phe Asp Leu Pro Leu Asp Gln Leu Gln Thr Tyr Lys Pro
1 5 10 15
Glu Lys Thr Ala Pro Lys Asp Phe Ser Glu Phe Trp Lys Leu Ser Leu
20 25 30
Glu Glu Leu Ala Lys Val Gln Ala Glu Pro Asp Leu Gln Pro Val Asp
35 40 45
Tyr Pro Ala Asp Gly Val Lys Val Tyr Arg Leu Thr Tyr Lys Ser Phe
50 55 60
Gly Asn Ala Arg Ile Thr Gly Trp Tyr Ala Val Pro Asp Lys Glu Gly
65 70 75 80
Pro His Pro Ala Ile Val Lys Tyr His Gly Tyr Asn Ala Ser Tyr Asp
85 90 95
Gly Glu Ile His Glu Met Val Asn Trp Ala Leu His Gly Tyr Ala Thr
100 105 110
Phe Gly Met Leu Val Arg Gly Gln Gln Ser Ser Glu Asp Thr Ser Ile
115 120 125
Ser Pro His Gly His Ala Leu Gly Trp Met Thr Lys Gly Ile Leu Asp
130 135 140
Lys Asp Thr Tyr Tyr Tyr Arg Gly Val Tyr Leu Asp Ala Val Arg Ala
145 150 155 160
Leu Glu Val Ile Ser Ser Phe Asp Glu Val Asp Glu Thr Arg Ile Gly
165 170 175
Val Thr Gly Gly Ser Gln Gly Gly Gly Leu Thr Ile Ala Ala Ala Ala
180 185 190
Leu Ser Asp Ile Pro Lys Ala Ala Val Ala Asp Tyr Pro Tyr Leu Ser
195 200 205
Asn Phe Glu Arg Ala Ile Asp Val Ala Leu Glu Gln Pro Tyr Leu Glu
210 215 220
Ile Asn Ser Phe Phe Arg Arg Asn Gly Ser Pro Glu Thr Glu Val Gln
225 230 235 240
Ala Met Lys Thr Leu Ser Tyr Phe Asp Ile Met Asn Leu Ala Asp Arg
245 250 255
Val Lys Val Pro Val Leu Met Ser Ile Gly Leu Ile Asp Lys Val Thr
260 265 270
Pro Pro Ser Thr Val Phe Ala Ala Tyr Asn His Leu Glu Thr Lys Lys
275 280 285
Glu Leu Lys Val Tyr Arg Tyr Phe Gly His Glu Tyr Ile Pro Ala Phe
290 295 300
Gln Thr Glu Lys Leu Ala Phe Phe Lys Gln His Leu Lys Gly
305 310 315
<210> 6
<211> 318
<212> PRT
<213> 枯草芽孢杆菌
<400> 6
Met Gln Leu Phe Asp Leu Pro Leu Asp Gln Leu Gln Thr Tyr Lys Pro
1 5 10 15
Glu Lys Thr Thr Pro Asn Asp Phe Ser Glu Phe Trp Lys Ser Ser Leu
20 25 30
Asp Glu Leu Ala Lys Val Lys Ala Ala Pro Asp Leu Gln Leu Val Asp
35 40 45
Tyr Pro Ala Asp Gly Val Lys Val Tyr Arg Leu Thr Tyr Lys Ser Phe
50 55 60
Gly Asn Ala Arg Ile Thr Gly Trp Tyr Ala Val Pro Asp Lys Glu Gly
65 70 75 80
Pro His Pro Ala Ile Val Lys Tyr His Gly Tyr Asn Ala Ser Tyr Asp
85 90 95
Gly Glu Ile His Glu Met Val Asn Trp Ala Leu His Gly Tyr Ala Ala
100 105 110
Phe Gly Met Leu Val Arg Gly Gln Gln Ser Ser Glu Asp Thr Ser Ile
115 120 125
Ser Pro His Gly His Ala Leu Gly Trp Met Thr Lys Gly Ile Leu Asp
130 135 140
Lys Asp Thr Tyr Tyr Tyr Arg Gly Val Tyr Leu Asp Ala Val Arg Ala
145 150 155 160
Leu Glu Val Ile Ser Ser Phe Asp Glu Val Asp Glu Thr Arg Ile Gly
165 170 175
Val Thr Gly Gly Ser Gln Gly Gly Gly Leu Thr Ile Ala Ala Ala Ala
180 185 190
Leu Ser Asp Ile Pro Lys Ala Ala Val Ala Asp Tyr Pro Tyr Leu Ser
195 200 205
Asn Phe Glu Arg Ala Ile Asp Val Ala Leu Glu Gln Pro Tyr Leu Glu
210 215 220
Ile Asn Ser Phe Phe Arg Arg Asn Gly Ser Pro Glu Thr Glu Glu Lys
225 230 235 240
Ala Met Lys Thr Leu Ser Tyr Phe Asp Ile Met Asn Leu Ala Asp Arg
245 250 255
Val Lys Val Pro Val Leu Met Ser Ile Gly Leu Ile Asp Lys Val Thr
260 265 270
Pro Pro Ser Thr Val Phe Ala Ala Tyr Asn His Leu Glu Thr Glu Lys
275 280 285
Glu Leu Lys Val Tyr Arg Tyr Phe Gly His Glu Tyr Ile Pro Ala Phe
290 295 300
Gln Thr Glu Lys Leu Ala Phe Phe Lys Gln His Leu Lys Gly
305 310 315
<210> 7
<211> 318
<212> PRT
<213> 地衣芽孢杆菌(Bacillus licheniformis)
<400> 7
Met Gln Gln Pro Tyr Asp Met Pro Leu Glu Gln Leu Tyr Gln Tyr Lys
1 5 10 15
Pro Glu Arg Thr Ala Pro Ala Asp Phe Lys Glu Phe Trp Lys Gly Ser
20 25 30
Leu Glu Glu Leu Ala Asn Glu Lys Ala Gly Pro Gln Leu Glu Pro His
35 40 45
Glu Tyr Pro Ala Asp Gly Val Lys Val Tyr Trp Leu Thr Tyr Arg Ser
50 55 60
Ile Gly Gly Ala Arg Ile Lys Gly Trp Tyr Ala Val Pro Asp Arg Gln
65 70 75 80
Gly Pro His Pro Ala Ile Val Lys Tyr His Gly Tyr Asn Ala Ser Tyr
85 90 95
Asp Gly Asp Ile His Asp Ile Val Asn Trp Ala Leu His Gly Tyr Ala
100 105 110
Ala Phe Gly Met Leu Val Arg Gly Gln Asn Ser Ser Glu Asp Thr Glu
115 120 125
Ile Ser His His Gly His Val Pro Gly Trp Met Thr Lys Gly Ile Leu
130 135 140
Asp Pro Lys Thr Tyr Tyr Tyr Arg Gly Val Tyr Leu Asp Ala Val Arg
145 150 155 160
Ala Val Glu Val Val Ser Gly Phe Ala Glu Val Asp Glu Lys Arg Ile
165 170 175
Gly Val Ile Gly Ala Ser Gln Gly Gly Gly Leu Ala Val Ala Val Ser
180 185 190
Ala Leu Ser Asp Ile Pro Lys Ala Ala Val Ser Glu Tyr Pro Tyr Leu
195 200 205
Ser Asn Phe Gln Arg Ala Ile Asp Thr Ala Ile Asp Gln Pro Tyr Leu
210 215 220
Glu Ile Asn Ser Phe Phe Arg Arg Asn Thr Ser Pro Asp Ile Glu Gln
225 230 235 240
Ala Ala Met His Thr Leu Ser Tyr Phe Asp Val Met Asn Leu Ala Gln
245 250 255
Leu Val Lys Ala Thr Val Leu Met Ser Ile Gly Leu Val Asp Thr Ile
260 265 270
Thr Pro Pro Ser Thr Val Phe Ala Ala Tyr Asn His Leu Glu Thr Asp
275 280 285
Lys Glu Ile Lys Val Tyr Arg Tyr Phe Gly His Glu Tyr Ile Pro Pro
290 295 300
Phe Gln Thr Glu Lys Leu Ala Phe Leu Arg Lys His Leu Lys
305 310 315
<210> 8
<211> 320
<212> PRT
<213> 短小芽孢杆菌(Bacillus pumilus)
<400> 8
Met Gln Leu Phe Asp Leu Ser Leu Glu Glu Leu Lys Lys Tyr Lys Pro
1 5 10 15
Lys Lys Thr Ala Arg Pro Asp Phe Ser Asp Phe Trp Lys Lys Ser Leu
20 25 30
Glu Glu Leu Arg Gln Val Glu Ala Glu Pro Thr Leu Glu Ser Tyr Asp
35 40 45
Tyr Pro Val Lys Gly Val Lys Val Tyr Arg Leu Thr Tyr Gln Ser Phe
50 55 60
Gly His Ser Lys Ile Glu Gly Phe Tyr Ala Val Pro Asp Gln Thr Gly
65 70 75 80
Pro His Pro Ala Leu Val Arg Phe His Gly Tyr Asn Ala Ser Tyr Asp
85 90 95
Gly Gly Ile His Asp Ile Val Asn Trp Ala Leu His Gly Tyr Ala Thr
100 105 110
Phe Gly Met Leu Val Arg Gly Gln Gly Gly Ser Glu Asp Thr Ser Val
115 120 125
Thr Pro Gly Gly His Ala Leu Gly Trp Met Thr Lys Gly Ile Leu Ser
130 135 140
Lys Asp Thr Tyr Tyr Tyr Arg Gly Val Tyr Leu Asp Ala Val Arg Ala
145 150 155 160
Leu Glu Val Ile Gln Ser Phe Pro Glu Val Asp Glu His Arg Ile Gly
165 170 175
Val Ile Gly Gly Ser Gln Gly Gly Ala Leu Ala Ile Ala Ala Ala Ala
180 185 190
Leu Ser Asp Ile Pro Lys Val Val Val Ala Asp Tyr Pro Tyr Leu Ser
195 200 205
Asn Phe Glu Arg Ala Val Asp Val Ala Leu Glu Gln Pro Tyr Leu Glu
210 215 220
Ile Asn Ser Tyr Phe Arg Arg Asn Ser Asp Pro Lys Val Glu Glu Lys
225 230 235 240
Ala Phe Glu Thr Leu Ser Tyr Phe Asp Leu Ile Asn Leu Ala Gly Trp
245 250 255
Val Lys Gln Pro Thr Leu Met Ala Ile Gly Leu Ile Asp Lys Ile Thr
260 265 270
Pro Pro Ser Thr Val Phe Ala Ala Tyr Asn His Leu Glu Thr Asp Lys
275 280 285
Asp Leu Lys Val Tyr Arg Tyr Phe Gly His Glu Phe Ile Pro Ala Phe
290 295 300
Gln Thr Glu Lys Leu Ser Phe Leu Gln Lys His Leu Leu Leu Ser Thr
305 310 315 320
<210> 9
<211> 320
<212> PRT
<213> 热解纤维梭菌(Clostridium thermocellum)
<400> 9
Met Ala Gln Leu Tyr Asp Met Pro Leu Glu Glu Leu Lys Lys Tyr Lys
1 5 10 15
Pro Ala Leu Thr Lys Gln Lys Asp Phe Asp Glu Phe Trp Glu Lys Ser
20 25 30
Leu Lys Glu Leu Ala Glu Ile Pro Leu Lys Tyr Gln Leu Ile Pro Tyr
35 40 45
Asp Phe Pro Ala Arg Arg Val Lys Val Phe Arg Val Glu Tyr Leu Gly
50 55 60
Phe Lys Gly Ala Asn Ile Glu Gly Trp Leu Ala Val Pro Glu Gly Glu
65 70 75 80
Gly Leu Tyr Pro Gly Leu Val Gln Phe His Gly Tyr Asn Trp Ala Met
85 90 95
Asp Gly Cys Val Pro Asp Val Val Asn Trp Ala Leu Asn Gly Tyr Ala
100 105 110
Ala Phe Leu Met Leu Val Arg Gly Gln Gln Gly Arg Ser Val Asp Asn
115 120 125
Ile Val Pro Gly Ser Gly His Ala Leu Gly Trp Met Ser Lys Gly Ile
130 135 140
Leu Ser Pro Glu Glu Tyr Tyr Tyr Arg Gly Val Tyr Met Asp Ala Val
145 150 155 160
Arg Ala Val Glu Ile Leu Ala Ser Leu Pro Cys Val Asp Glu Ser Arg
165 170 175
Ile Gly Val Thr Gly Gly Ser Gln Gly Gly Gly Leu Ala Leu Ala Val
180 185 190
Ala Ala Leu Ser Gly Ile Pro Lys Val Ala Ala Val His Tyr Pro Phe
195 200 205
Leu Ala His Phe Glu Arg Ala Ile Asp Val Ala Pro Asp Gly Pro Tyr
210 215 220
Leu Glu Ile Asn Glu Tyr Leu Arg Arg Asn Ser Gly Glu Glu Ile Glu
225 230 235 240
Arg Gln Val Lys Lys Thr Leu Ser Tyr Phe Asp Ile Met Asn Leu Ala
245 250 255
Pro Arg Ile Lys Cys Arg Thr Trp Ile Cys Thr Gly Leu Val Asp Glu
260 265 270
Ile Thr Pro Pro Ser Thr Val Phe Ala Val Tyr Asn His Leu Lys Cys
275 280 285
Pro Lys Glu Ile Ser Val Phe Arg Tyr Phe Gly His Glu His Met Pro
290 295 300
Gly Ser Val Glu Ile Lys Leu Arg Ile Leu Met Asp Glu Leu Asn Pro
305 310 315 320
<210> 10
<211> 325
<212> PRT
<213> 那不勒斯栖热袍菌(Thermotoga neapolitana)
<400> 10
Met Ala Phe Phe Asp Met Pro Leu Glu Glu Leu Lys Lys Tyr Arg Pro
1 5 10 15
Glu Arg Tyr Glu Glu Lys Asp Phe Asp Glu Phe Trp Arg Glu Thr Leu
20 25 30
Lys Glu Ser Glu Gly Phe Pro Leu Asp Pro Val Phe Glu Lys Val Asp
35 40 45
Phe His Leu Lys Thr Val Glu Thr Tyr Asp Val Thr Phe Ser Gly Tyr
50 55 60
Arg Gly Gln Arg Ile Lys Gly Trp Leu Leu Val Pro Lys Leu Ala Glu
65 70 75 80
Glu Lys Leu Pro Cys Val Val Gln Tyr Ile Gly Tyr Asn Gly Gly Arg
85 90 95
Gly Phe Pro His Asp Trp Leu Phe Trp Pro Ser Met Gly Tyr Ile Cys
100 105 110
Phe Val Met Asp Thr Arg Gly Gln Gly Ser Gly Trp Met Lys Gly Asp
115 120 125
Thr Pro Asp Tyr Pro Glu Gly Pro Val Asp Pro Gln Tyr Pro Gly Phe
130 135 140
Met Thr Arg Gly Ile Leu Asp Pro Gly Thr Tyr Tyr Tyr Arg Arg Val
145 150 155 160
Phe Val Asp Ala Val Arg Ala Val Glu Ala Ala Ile Ser Phe Pro Arg
165 170 175
Val Asp Ser Arg Lys Val Val Val Ala Gly Gly Ser Gln Gly Gly Gly
180 185 190
Ile Ala Leu Ala Val Ser Ala Leu Ser Asn Arg Val Lys Ala Leu Leu
195 200 205
Cys Asp Val Pro Phe Leu Cys His Phe Arg Arg Ala Val Gln Leu Val
210 215 220
Asp Thr His Pro Tyr Val Glu Ile Thr Asn Phe Leu Lys Thr His Arg
225 230 235 240
Asp Lys Glu Glu Ile Val Phe Arg Thr Leu Ser Tyr Phe Asp Gly Val
245 250 255
Asn Phe Ala Ala Arg Ala Lys Val Pro Ala Leu Phe Ser Val Gly Leu
260 265 270
Met Asp Thr Ile Cys Pro Pro Ser Thr Val Phe Ala Ala Tyr Asn His
275 280 285
Tyr Ala Gly Pro Lys Glu Ile Arg Ile Tyr Pro Tyr Asn Asn His Glu
290 295 300
Gly Gly Gly Ser Phe Gln Ala Ile Glu Gln Val Lys Phe Leu Lys Arg
305 310 315 320
Leu Phe Glu Glu Gly
325
<210> 11
<211> 325
<212> PRT
<213> 海栖热袍菌
<400> 11
Met Ala Phe Phe Asp Leu Pro Leu Glu Glu Leu Lys Lys Tyr Arg Pro
1 5 10 15
Glu Arg Tyr Glu Glu Lys Asp Phe Asp Glu Phe Trp Glu Glu Thr Leu
20 25 30
Ala Glu Ser Glu Lys Phe Pro Leu Asp Pro Val Phe Glu Arg Met Glu
35 40 45
Ser His Leu Lys Thr Val Glu Ala Tyr Asp Val Thr Phe Ser Gly Tyr
50 55 60
Arg Gly Gln Arg Ile Lys Gly Trp Leu Leu Val Pro Lys Leu Glu Glu
65 70 75 80
Glu Lys Leu Pro Cys Val Val Gln Tyr Ile Gly Tyr Asn Gly Gly Arg
85 90 95
Gly Phe Pro His Asp Trp Leu Phe Trp Pro Ser Met Gly Tyr Ile Cys
100 105 110
Phe Val Met Asp Thr Arg Gly Gln Gly Ser Gly Trp Leu Lys Gly Asp
115 120 125
Thr Pro Asp Tyr Pro Glu Gly Pro Val Asp Pro Gln Tyr Pro Gly Phe
130 135 140
Met Thr Arg Gly Ile Leu Asp Pro Arg Thr Tyr Tyr Tyr Arg Arg Val
145 150 155 160
Phe Thr Asp Ala Val Arg Ala Val Glu Ala Ala Ala Ser Phe Pro Gln
165 170 175
Val Asp Gln Glu Arg Ile Val Ile Ala Gly Gly Ser Gln Gly Gly Gly
180 185 190
Ile Ala Leu Ala Val Ser Ala Leu Ser Lys Lys Ala Lys Ala Leu Leu
195 200 205
Cys Asp Val Pro Phe Leu Cys His Phe Arg Arg Ala Val Gln Leu Val
210 215 220
Asp Thr His Pro Tyr Ala Glu Ile Thr Asn Phe Leu Lys Thr His Arg
225 230 235 240
Asp Lys Glu Glu Ile Val Phe Arg Thr Leu Ser Tyr Phe Asp Gly Val
245 250 255
Asn Phe Ala Ala Arg Ala Lys Ile Pro Ala Leu Phe Ser Val Gly Leu
260 265 270
Met Asp Asn Ile Cys Pro Pro Ser Thr Val Phe Ala Ala Tyr Asn Tyr
275 280 285
Tyr Ala Gly Pro Lys Glu Ile Arg Ile Tyr Pro Tyr Asn Asn His Glu
290 295 300
Gly Gly Gly Ser Phe Gln Ala Val Glu Gln Val Lys Phe Leu Lys Lys
305 310 315 320
Leu Phe Glu Lys Gly
325
<210> 12
<211> 320
<212> PRT
<213> 热厌氧杆菌属菌种(Thermoanaerobacterium sp.)
<400> 12
Met Gly Leu Phe Asp Met Pro Leu Gln Lys Leu Arg Glu Tyr Thr Gly
1 5 10 15
Thr Asn Pro Cys Pro Glu Asp Phe Asp Glu Tyr Trp Asn Arg Ala Leu
20 25 30
Asp Glu Met Arg Ser Val Asp Pro Lys Ile Glu Leu Lys Glu Ser Ser
35 40 45
Phe Gln Val Ser Phe Ala Glu Cys Tyr Asp Leu Tyr Phe Thr Gly Val
50 55 60
Arg Gly Ala Arg Ile His Ala Lys Tyr Ile Lys Pro Lys Thr Glu Gly
65 70 75 80
Lys His Pro Ala Leu Ile Arg Phe His Gly Tyr Ser Ser Asn Ser Gly
85 90 95
Asp Trp Asn Asp Lys Leu Asn Tyr Val Ala Ala Gly Phe Thr Val Val
100 105 110
Ala Met Asp Val Arg Gly Gln Gly Gly Gln Ser Gln Asp Val Gly Gly
115 120 125
Val Thr Gly Asn Thr Leu Asn Gly His Ile Ile Arg Gly Leu Asp Asp
130 135 140
Asp Ala Asp Asn Met Leu Phe Arg His Ile Phe Leu Asp Thr Ala Gln
145 150 155 160
Leu Ala Gly Ile Val Met Asn Met Pro Glu Val Asp Glu Asp Arg Val
165 170 175
Gly Val Met Gly Pro Ser Gln Gly Gly Gly Leu Ser Leu Ala Cys Ala
180 185 190
Ala Leu Glu Pro Arg Val Arg Lys Val Val Ser Glu Tyr Pro Phe Leu
195 200 205
Ser Asp Tyr Lys Arg Val Trp Asp Leu Asp Leu Ala Lys Asn Ala Tyr
210 215 220
Gln Glu Ile Thr Asp Tyr Phe Arg Leu Phe Asp Pro Arg His Glu Arg
225 230 235 240
Glu Asn Glu Val Phe Thr Lys Leu Gly Tyr Ile Asp Val Lys Asn Leu
245 250 255
Ala Lys Arg Ile Lys Gly Asp Val Leu Met Cys Val Gly Leu Met Asp
260 265 270
Gln Val Cys Pro Pro Ser Thr Val Phe Ala Ala Tyr Asn Asn Ile Gln
275 280 285
Ser Lys Lys Asp Ile Lys Val Tyr Pro Asp Tyr Gly His Glu Pro Met
290 295 300
Arg Gly Phe Gly Asp Leu Ala Met Gln Phe Met Leu Glu Leu Tyr Ser
305 310 315 320
<210> 13
<211> 319
<212> PRT
<213> 耐盐芽孢杆菌(Bacillus halodurans)
<400> 13
Met Pro Leu Ile Asp Met Pro Leu Thr Glu Leu Lys Glu Tyr Met Gly
1 5 10 15
Arg Asn Pro Lys Pro Asp Asp Phe Thr Glu Tyr Trp Asp Arg Ala Leu
20 25 30
Gln Glu Met Arg Lys Val Asn Pro Asn Val Glu Leu Ile Pro Ser Asp
35 40 45
Phe Gln Thr Thr Tyr Ala Glu Cys Phe His Leu Tyr Phe Thr Gly Val
50 55 60
Arg Gly Ala Arg Ile His Ala Lys Tyr Val Arg Pro Arg His Thr Ser
65 70 75 80
Gly Thr His Pro Ala Val Ile His Phe His Gly Tyr Thr Met Asn Ala
85 90 95
Gly Glu Trp Thr Gly Leu Leu His Tyr Ala Ala Leu Gly Tyr Ser Val
100 105 110
Leu Ala Met Asp Val Arg Gly Gln Gly Gly Leu Ser Glu Asp Thr Gly
115 120 125
Gly Val Lys Gly Asn Thr His Ser Gly His Ile Ile Arg Gly Leu Asp
130 135 140
Asp Asn Ala Asp Gln Leu Leu Phe Arg His Val Phe Leu Asp Thr Ala
145 150 155 160
Gln Leu Ala Asn Ile Val Met Asn Leu Pro Glu Val Asp Glu Glu Arg
165 170 175
Val Ala Val Thr Gly Trp Ser Gln Gly Gly Ala Leu Ala Ile Ala Cys
180 185 190
Ala Ala Leu Glu Pro Lys Ile Lys Lys Val Ala Pro Val Tyr Pro Phe
195 200 205
Leu Ser Asp Tyr Gln Arg Val Trp Glu Met Asp Leu Ala Glu Lys Ala
210 215 220
Tyr Asp Glu Leu Gln Thr Tyr Phe Arg Arg Phe Asp Pro Gln His Arg
225 230 235 240
Arg Glu Ala Glu Ile Phe Thr Lys Leu Gly Tyr Ile Asp Ile Gln His
245 250 255
Leu Ala Pro Leu Val Lys Gly Glu Val Leu Leu Ala Val Gly Leu Met
260 265 270
Asp Thr Val Cys Pro Pro Ser Thr Gln Phe Ala Met Tyr Asn Lys Leu
275 280 285
Thr Thr Thr Lys Ser Ile Glu Leu Tyr Pro Asp Phe Ala His Glu Asp
290 295 300
Leu Pro Gly His Arg Asp Arg Ile Phe Gln Phe Leu Ser Asp Leu
305 310 315
<210> 14
<211> 317
<212> PRT
<213> 克劳氏芽孢杆菌(Bacillus clausii)
<400> 14
Met Pro Leu Val Asp Met Pro Leu Arg Glu Leu Leu Ala Tyr Glu Gly
1 5 10 15
Ile Asn Pro Lys Pro Ala Asp Phe Asp Gln Tyr Trp Asn Arg Ala Lys
20 25 30
Thr Glu Ile Glu Ala Ile Asp Pro Glu Val Thr Leu Val Glu Ser Ser
35 40 45
Phe Gln Cys Ser Phe Ala Asn Cys Tyr His Phe Tyr Tyr Arg Ser Ala
50 55 60
Gly Asn Ala Lys Ile His Ala Lys Tyr Val Gln Pro Lys Ala Gly Glu
65 70 75 80
Lys Thr Pro Ala Val Phe Met Phe His Gly Tyr Gly Gly Arg Ser Ala
85 90 95
Glu Trp Ser Ser Leu Leu Asn Tyr Val Ala Ala Gly Phe Ser Val Phe
100 105 110
Tyr Met Asp Val Arg Gly Gln Gly Gly Thr Ser Glu Asp Pro Gly Gly
115 120 125
Val Arg Gly Asn Thr Tyr Arg Gly His Ile Ile Arg Gly Leu Asp Ala
130 135 140
Gly Pro Asp Ala Leu Phe Tyr Arg Ser Val Phe Leu Asp Thr Val Gln
145 150 155 160
Leu Val Arg Ala Ala Lys Thr Leu Pro His Ile Asp Lys Thr Arg Leu
165 170 175
Met Ala Thr Gly Trp Ser Gln Gly Gly Ala Leu Thr Leu Ala Cys Ala
180 185 190
Ala Leu Val Pro Glu Ile Lys Arg Leu Ala Pro Val Tyr Pro Phe Leu
195 200 205
Ser Asp Tyr Lys Arg Val Trp Gln Met Asp Leu Ala Val Arg Ser Tyr
210 215 220
Lys Glu Leu Ala Asp Tyr Phe Arg Ser Tyr Asp Pro Gln His Lys Arg
225 230 235 240
His Gly Glu Ile Phe Glu Arg Leu Gly Tyr Ile Asp Val Gln His Leu
245 250 255
Ala Asp Arg Ile Gln Gly Asp Val Leu Met Gly Val Gly Leu Met Asp
260 265 270
Thr Glu Cys Pro Pro Ser Thr Gln Phe Ala Ala Tyr Asn Lys Ile Lys
275 280 285
Ala Lys Lys Ser Tyr Glu Leu Tyr Pro Asp Phe Gly His Glu His Leu
290 295 300
Pro Gly Met Asn Asp His Ile Phe Arg Phe Phe Thr Ser
305 310 315
<210> 15
<211> 325
<212> PRT
<213> 那不勒斯栖热袍菌
<220>
<221> 其他特征
<222> (277)..(277)
<223> Xaa是Ala、Val、Ser或Thr
<400> 15
Met Ala Phe Phe Asp Met Pro Leu Glu Glu Leu Lys Lys Tyr Arg Pro
1 5 10 15
Glu Arg Tyr Glu Glu Lys Asp Phe Asp Glu Phe Trp Arg Glu Thr Leu
20 25 30
Lys Glu Ser Glu Gly Phe Pro Leu Asp Pro Val Phe Glu Lys Val Asp
35 40 45
Phe His Leu Lys Thr Val Glu Thr Tyr Asp Val Thr Phe Ser Gly Tyr
50 55 60
Arg Gly Gln Arg Ile Lys Gly Trp Leu Leu Val Pro Lys Leu Ala Glu
65 70 75 80
Glu Lys Leu Pro Cys Val Val Gln Tyr Ile Gly Tyr Asn Gly Gly Arg
85 90 95
Gly Phe Pro His Asp Trp Leu Phe Trp Pro Ser Met Gly Tyr Ile Cys
100 105 110
Phe Val Met Asp Thr Arg Gly Gln Gly Ser Gly Trp Met Lys Gly Asp
115 120 125
Thr Pro Asp Tyr Pro Glu Gly Pro Val Asp Pro Gln Tyr Pro Gly Phe
130 135 140
Met Thr Arg Gly Ile Leu Asp Pro Gly Thr Tyr Tyr Tyr Arg Arg Val
145 150 155 160
Phe Val Asp Ala Val Arg Ala Val Glu Ala Ala Ile Ser Phe Pro Arg
165 170 175
Val Asp Ser Arg Lys Val Val Val Ala Gly Gly Ser Gln Gly Gly Gly
180 185 190
Ile Ala Leu Ala Val Ser Ala Leu Ser Asn Arg Val Lys Ala Leu Leu
195 200 205
Cys Asp Val Pro Phe Leu Cys His Phe Arg Arg Ala Val Gln Leu Val
210 215 220
Asp Thr His Pro Tyr Val Glu Ile Thr Asn Phe Leu Lys Thr His Arg
225 230 235 240
Asp Lys Glu Glu Ile Val Phe Arg Thr Leu Ser Tyr Phe Asp Gly Val
245 250 255
Asn Phe Ala Ala Arg Ala Lys Val Pro Ala Leu Phe Ser Val Gly Leu
260 265 270
Met Asp Thr Ile Xaa Pro Pro Ser Thr Val Phe Ala Ala Tyr Asn His
275 280 285
Tyr Ala Gly Pro Lys Glu Ile Arg Ile Tyr Pro Tyr Asn Asn His Glu
290 295 300
Gly Gly Gly Ser Phe Gln Ala Ile Glu Gln Val Lys Phe Leu Lys Arg
305 310 315 320
Leu Phe Glu Glu Gly
325
<210> 16
<211> 325
<212> PRT
<213> 海栖热袍菌
<220>
<221> 其他特征
<222> (277)..(277)
<223> Xaa是Ala、Val、Ser或Thr
<400> 16
Met Ala Phe Phe Asp Leu Pro Leu Glu Glu Leu Lys Lys Tyr Arg Pro
1 5 10 15
Glu Arg Tyr Glu Glu Lys Asp Phe Asp Glu Phe Trp Glu Glu Thr Leu
20 25 30
Ala Glu Ser Glu Lys Phe Pro Leu Asp Pro Val Phe Glu Arg Met Glu
35 40 45
Ser His Leu Lys Thr Val Glu Ala Tyr Asp Val Thr Phe Ser Gly Tyr
50 55 60
Arg Gly Gln Arg Ile Lys Gly Trp Leu Leu Val Pro Lys Leu Glu Glu
65 70 75 80
Glu Lys Leu Pro Cys Val Val Gln Tyr Ile Gly Tyr Asn Gly Gly Arg
85 90 95
Gly Phe Pro His Asp Trp Leu Phe Trp Pro Ser Met Gly Tyr Ile Cys
100 105 110
Phe Val Met Asp Thr Arg Gly Gln Gly Ser Gly Trp Leu Lys Gly Asp
115 120 125
Thr Pro Asp Tyr Pro Glu Gly Pro Val Asp Pro Gln Tyr Pro Gly Phe
130 135 140
Met Thr Arg Gly Ile Leu Asp Pro Arg Thr Tyr Tyr Tyr Arg Arg Val
145 150 155 160
Phe Thr Asp Ala Val Arg Ala Val Glu Ala Ala Ala Ser Phe Pro Gln
165 170 175
Val Asp Gln Glu Arg Ile Val Ile Ala Gly Gly Ser Gln Gly Gly Gly
180 185 190
Ile Ala Leu Ala Val Ser Ala Leu Ser Lys Lys Ala Lys Ala Leu Leu
195 200 205
Cys Asp Val Pro Phe Leu Cys His Phe Arg Arg Ala Val Gln Leu Val
210 215 220
Asp Thr His Pro Tyr Ala Glu Ile Thr Asn Phe Leu Lys Thr His Arg
225 230 235 240
Asp Lys Glu Glu Ile Val Phe Arg Thr Leu Ser Tyr Phe Asp Gly Val
245 250 255
Asn Phe Ala Ala Arg Ala Lys Ile Pro Ala Leu Phe Ser Val Gly Leu
260 265 270
Met Asp Asn Ile Xaa Pro Pro Ser Thr Val Phe Ala Ala Tyr Asn Tyr
275 280 285
Tyr Ala Gly Pro Lys Glu Ile Arg Ile Tyr Pro Tyr Asn Asn His Glu
290 295 300
Gly Gly Gly Ser Phe Gln Ala Val Glu Gln Val Lys Phe Leu Lys Lys
305 310 315 320
Leu Phe Glu Lys Gly
325
<210> 17
<211> 326
<212> PRT
<213> 莱廷格栖热袍菌(Thermotoga lettingae)
<220>
<221> 其他特征
<222> (277)..(277)
<223> Xaa是Ala、Val、Ser或Thr
<400> 17
Met Val Tyr Phe Asp Met Pro Leu Glu Asp Leu Arg Lys Tyr Leu Pro
1 5 10 15
Gln Arg Tyr Glu Glu Lys Asp Phe Asp Asp Phe Trp Lys Gln Thr Ile
20 25 30
His Glu Thr Arg Gly Tyr Phe Gln Glu Pro Ile Leu Lys Lys Val Asp
35 40 45
Phe Tyr Leu Gln Asn Val Glu Thr Phe Asp Val Thr Phe Ser Gly Tyr
50 55 60
Arg Gly Gln Lys Ile Lys Gly Trp Leu Ile Leu Pro Lys Phe Arg Asn
65 70 75 80
Gly Lys Leu Pro Cys Val Val Glu Phe Val Gly Tyr Gly Gly Gly Arg
85 90 95
Gly Phe Pro Tyr Asp Trp Leu Leu Trp Ser Ala Ala Gly Tyr Ala His
100 105 110
Phe Ile Met Asp Thr Arg Gly Gln Gly Ser Asn Trp Met Lys Gly Asp
115 120 125
Thr Pro Asp Tyr Glu Asp Asn Pro Ser Asp Pro Gln Tyr Pro Gly Phe
130 135 140
Leu Thr Lys Gly Val Leu Asn Pro Glu Thr Tyr Tyr Tyr Arg Arg Val
145 150 155 160
Phe Met Asp Ala Phe Met Ala Val Glu Thr Ile Ser Gln Leu Glu Gln
165 170 175
Ile Asp Ser Gln Thr Ile Ile Leu Ser Gly Ala Ser Gln Gly Gly Gly
180 185 190
Ile Ala Leu Ala Val Ser Ala Leu Ser Ser Lys Val Met Ala Leu Leu
195 200 205
Cys Asp Val Pro Phe Leu Cys His Tyr Lys Arg Ala Val Gln Ile Thr
210 215 220
Asp Ser Met Pro Tyr Ala Glu Ile Thr Arg Tyr Cys Lys Thr His Ile
225 230 235 240
Asp Lys Ile Gln Thr Val Phe Arg Thr Leu Ser Tyr Phe Asp Gly Val
245 250 255
Asn Phe Ala Ala Arg Ala Lys Cys Pro Ala Leu Phe Ser Val Gly Leu
260 265 270
Met Asp Asp Ile Xaa Pro Pro Ser Thr Val Phe Ala Ala Tyr Asn Tyr
275 280 285
Tyr Ala Gly Glu Lys Asp Ile Arg Ile Tyr Pro Tyr Asn Asn His Glu
290 295 300
Gly Gly Gly Ser Phe His Thr Leu Glu Lys Leu Lys Phe Val Lys Lys
305 310 315 320
Thr Ile Ser Met Arg Glu
325
<210> 18
<211> 325
<212> PRT
<213> 嗜石油栖热袍菌(Thermotoga petrophilia)
<220>
<221> 其他特征
<222> (277)..(277)
<223> Xaa是Ala、Val、Ser或Thr
<400> 18
Met Ala Phe Phe Asp Leu Pro Leu Glu Glu Leu Lys Lys Tyr Arg Pro
1 5 10 15
Glu Arg Tyr Glu Glu Lys Asp Phe Asp Glu Phe Trp Glu Gly Thr Leu
20 25 30
Ala Glu Asn Glu Lys Phe Pro Leu Asp Pro Val Phe Glu Arg Met Glu
35 40 45
Ser His Leu Lys Thr Val Glu Ala Tyr Asp Val Thr Phe Ser Gly Tyr
50 55 60
Met Gly Gln Arg Ile Lys Gly Trp Leu Leu Val Pro Lys Leu Glu Glu
65 70 75 80
Glu Lys Leu Pro Cys Val Val Gln Tyr Ile Gly Tyr Asn Gly Gly Arg
85 90 95
Gly Phe Pro His Asp Trp Leu Phe Trp Pro Ser Met Gly Tyr Ile Cys
100 105 110
Phe Val Met Asp Thr Arg Gly Gln Gly Ser Gly Trp Met Lys Gly Asp
115 120 125
Thr Pro Asp Tyr Pro Glu Asp Pro Val Asp Pro Gln Tyr Pro Gly Phe
130 135 140
Met Thr Arg Gly Ile Leu Asp Pro Arg Thr Tyr Tyr Tyr Arg Arg Val
145 150 155 160
Phe Thr Asp Ala Val Arg Ala Val Glu Ala Ala Ala Ser Phe Pro Arg
165 170 175
Val Asp His Glu Arg Ile Val Ile Ala Gly Gly Ser Gln Gly Gly Gly
180 185 190
Ile Ala Leu Ala Val Ser Ala Leu Ser Lys Lys Ala Lys Ala Leu Leu
195 200 205
Cys Asp Val Pro Phe Leu Cys His Phe Arg Arg Ala Val Gln Leu Val
210 215 220
Asp Thr His Pro Tyr Ala Glu Ile Thr Asn Phe Leu Lys Thr His Arg
225 230 235 240
Asp Lys Glu Glu Ile Val Phe Arg Thr Leu Ser Tyr Phe Asp Gly Val
245 250 255
Asn Phe Ala Val Arg Ala Lys Ile Pro Ala Leu Phe Ser Val Gly Leu
260 265 270
Met Asp Asn Ile Xaa Pro Pro Ser Thr Val Phe Ala Ala Tyr Asn His
275 280 285
Tyr Ala Gly Pro Lys Glu Ile Arg Ile Tyr Pro Tyr Asn Asn His Glu
290 295 300
Gly Gly Gly Ser Phe Gln Ala Ile Glu Gln Val Lys Phe Leu Lys Arg
305 310 315 320
Leu Phe Glu Lys Gly
325
<210> 19
<211> 325
<212> PRT
<213> 栖热袍菌属菌种(Thermotoga sp.) RQ2a
<220>
<221> 其他特征
<222> (277)..(277)
<223> Xaa是Ala、Val、Ser或Thr
<400> 19
Met Ala Phe Phe Asp Leu Pro Leu Glu Glu Leu Lys Lys Tyr Arg Pro
1 5 10 15
Glu Arg Tyr Glu Glu Lys Asp Phe Asp Glu Phe Trp Lys Glu Thr Leu
20 25 30
Ala Glu Ser Glu Lys Phe Pro Leu Asp Pro Val Phe Glu Arg Met Glu
35 40 45
Ser His Leu Lys Thr Val Glu Val Tyr Asp Val Thr Phe Ser Gly Tyr
50 55 60
Arg Gly Gln Arg Ile Lys Gly Trp Leu Leu Val Pro Lys Leu Glu Glu
65 70 75 80
Glu Lys Leu Pro Cys Val Val Gln Tyr Ile Gly Tyr Asn Gly Gly Arg
85 90 95
Gly Phe Pro His Asp Trp Leu Phe Trp Pro Ser Met Gly Tyr Ile Cys
100 105 110
Phe Val Met Asp Thr Arg Gly Gln Gly Ser Gly Trp Leu Lys Gly Asp
115 120 125
Thr Pro Asp Tyr Pro Glu Asp Pro Val Asp Pro Gln Tyr Pro Gly Phe
130 135 140
Met Thr Arg Gly Ile Leu Asp Pro Arg Thr Tyr Tyr Tyr Arg Arg Val
145 150 155 160
Phe Thr Asp Ala Val Arg Ala Val Glu Ala Ala Ala Ser Phe Pro Arg
165 170 175
Val Asp His Glu Arg Ile Val Ile Ala Gly Gly Ser Gln Gly Gly Gly
180 185 190
Ile Ala Leu Ala Val Ser Ala Leu Ser Lys Lys Ala Lys Ala Leu Leu
195 200 205
Cys Asp Val Pro Phe Leu Cys His Phe Arg Arg Ala Val Gln Leu Val
210 215 220
Asp Thr His Pro Tyr Ala Glu Ile Thr Asn Phe Leu Lys Thr His Arg
225 230 235 240
Asp Lys Glu Glu Ile Val Phe Arg Thr Leu Ser Tyr Phe Asp Gly Val
245 250 255
Asn Phe Ala Val Arg Ala Lys Ile Pro Ala Leu Phe Ser Val Gly Leu
260 265 270
Met Asp Asn Ile Xaa Pro Pro Ser Thr Val Phe Ala Ala Tyr Asn His
275 280 285
Tyr Ala Gly Pro Lys Glu Ile Arg Ile Tyr Pro Tyr Asn Asn His Glu
290 295 300
Gly Gly Gly Ser Phe Gln Ala Ile Glu Gln Val Lys Phe Leu Lys Arg
305 310 315 320
Leu Phe Glu Lys Gly
325
<210> 20
<211> 329
<212> PRT
<213> 栖热袍菌属菌种RQ2b
<220>
<221> 其他特征
<222> (278)..(278)
<223> Xaa是Ala、Val、Ser或Thr
<400> 20
Met Ala Leu Phe Asp Met Pro Leu Glu Lys Leu Arg Ser Tyr Leu Pro
1 5 10 15
Asp Arg Tyr Glu Glu Glu Asp Phe Asp Leu Phe Trp Lys Glu Thr Leu
20 25 30
Glu Glu Ser Arg Lys Phe Pro Leu Asp Pro Ile Phe Glu Arg Val Asp
35 40 45
Tyr Leu Leu Glu Asn Val Glu Val Tyr Asp Val Thr Phe Ser Gly Tyr
50 55 60
Arg Gly Gln Arg Ile Lys Ala Trp Leu Ile Leu Pro Val Val Lys Lys
65 70 75 80
Glu Glu Arg Leu Pro Cys Ile Val Glu Phe Ile Gly Tyr Arg Gly Gly
85 90 95
Arg Gly Phe Pro Phe Asp Trp Leu Phe Trp Ser Ser Ala Gly Tyr Ala
100 105 110
His Phe Val Met Asp Thr Arg Gly Gln Gly Thr Ser Arg Val Lys Gly
115 120 125
Asp Thr Pro Asp Tyr Cys Asp Glu Pro Ile Asn Pro Gln Phe Pro Gly
130 135 140
Phe Met Thr Arg Gly Ile Leu Asp Pro Arg Thr Tyr Tyr Tyr Arg Arg
145 150 155 160
Val Phe Thr Asp Ala Val Arg Ala Val Glu Thr Ala Ser Ser Phe Pro
165 170 175
Gly Ile Asp Pro Glu Arg Ile Ala Val Val Gly Thr Ser Gln Gly Gly
180 185 190
Gly Ile Ala Leu Ala Val Ala Ala Leu Ser Glu Ile Pro Lys Ala Leu
195 200 205
Val Ser Asn Val Pro Phe Leu Cys His Phe Arg Arg Ala Val Gln Ile
210 215 220
Thr Asp Asn Ala Pro Tyr Ser Glu Ile Val Asn Tyr Leu Lys Val His
225 230 235 240
Arg Asp Lys Glu Glu Ile Val Phe Arg Thr Leu Ser Tyr Phe Asp Gly
245 250 255
Val Asn Phe Ala Ala Arg Ala Lys Ile Pro Ala Leu Phe Ser Val Ala
260 265 270
Leu Met Asp Lys Thr Xaa Pro Pro Ser Thr Val Phe Ala Ala Tyr Asn
275 280 285
His Tyr Ala Gly Pro Lys Glu Ile Lys Val Tyr Pro Phe Asn Glu His
290 295 300
Glu Gly Gly Glu Ser Phe Gln Arg Met Glu Glu Leu Arg Phe Met Lys
305 310 315 320
Arg Ile Leu Lys Gly Glu Phe Lys Ala
325
<210> 21
<211> 326
<212> PRT
<213> 莱廷格栖热袍菌
<400> 21
Met Val Tyr Phe Asp Met Pro Leu Glu Asp Leu Arg Lys Tyr Leu Pro
1 5 10 15
Gln Arg Tyr Glu Glu Lys Asp Phe Asp Asp Phe Trp Lys Gln Thr Ile
20 25 30
His Glu Thr Arg Gly Tyr Phe Gln Glu Pro Ile Leu Lys Lys Val Asp
35 40 45
Phe Tyr Leu Gln Asn Val Glu Thr Phe Asp Val Thr Phe Ser Gly Tyr
50 55 60
Arg Gly Gln Lys Ile Lys Gly Trp Leu Ile Leu Pro Lys Phe Arg Asn
65 70 75 80
Gly Lys Leu Pro Cys Val Val Glu Phe Val Gly Tyr Gly Gly Gly Arg
85 90 95
Gly Phe Pro Tyr Asp Trp Leu Leu Trp Ser Ala Ala Gly Tyr Ala His
100 105 110
Phe Ile Met Asp Thr Arg Gly Gln Gly Ser Asn Trp Met Lys Gly Asp
115 120 125
Thr Pro Asp Tyr Glu Asp Asn Pro Ser Asp Pro Gln Tyr Pro Gly Phe
130 135 140
Leu Thr Lys Gly Val Leu Asn Pro Glu Thr Tyr Tyr Tyr Arg Arg Val
145 150 155 160
Phe Met Asp Ala Phe Met Ala Val Glu Thr Ile Ser Gln Leu Glu Gln
165 170 175
Ile Asp Ser Gln Thr Ile Ile Leu Ser Gly Ala Ser Gln Gly Gly Gly
180 185 190
Ile Ala Leu Ala Val Ser Ala Leu Ser Ser Lys Val Met Ala Leu Leu
195 200 205
Cys Asp Val Pro Phe Leu Cys His Tyr Lys Arg Ala Val Gln Ile Thr
210 215 220
Asp Ser Met Pro Tyr Ala Glu Ile Thr Arg Tyr Cys Lys Thr His Ile
225 230 235 240
Asp Lys Ile Gln Thr Val Phe Arg Thr Leu Ser Tyr Phe Asp Gly Val
245 250 255
Asn Phe Ala Ala Arg Ala Lys Cys Pro Ala Leu Phe Ser Val Gly Leu
260 265 270
Met Asp Asp Ile Cys Pro Pro Ser Thr Val Phe Ala Ala Tyr Asn Tyr
275 280 285
Tyr Ala Gly Glu Lys Asp Ile Arg Ile Tyr Pro Tyr Asn Asn His Glu
290 295 300
Gly Gly Gly Ser Phe His Thr Leu Glu Lys Leu Lys Phe Val Lys Lys
305 310 315 320
Thr Ile Ser Met Arg Glu
325
<210> 22
<211> 325
<212> PRT
<213> 嗜石油栖热袍菌
<400> 22
Met Ala Phe Phe Asp Leu Pro Leu Glu Glu Leu Lys Lys Tyr Arg Pro
1 5 10 15
Glu Arg Tyr Glu Glu Lys Asp Phe Asp Glu Phe Trp Glu Gly Thr Leu
20 25 30
Ala Glu Asn Glu Lys Phe Pro Leu Asp Pro Val Phe Glu Arg Met Glu
35 40 45
Ser His Leu Lys Thr Val Glu Ala Tyr Asp Val Thr Phe Ser Gly Tyr
50 55 60
Met Gly Gln Arg Ile Lys Gly Trp Leu Leu Val Pro Lys Leu Glu Glu
65 70 75 80
Glu Lys Leu Pro Cys Val Val Gln Tyr Ile Gly Tyr Asn Gly Gly Arg
85 90 95
Gly Phe Pro His Asp Trp Leu Phe Trp Pro Ser Met Gly Tyr Ile Cys
100 105 110
Phe Val Met Asp Thr Arg Gly Gln Gly Ser Gly Trp Met Lys Gly Asp
115 120 125
Thr Pro Asp Tyr Pro Glu Asp Pro Val Asp Pro Gln Tyr Pro Gly Phe
130 135 140
Met Thr Arg Gly Ile Leu Asp Pro Arg Thr Tyr Tyr Tyr Arg Arg Val
145 150 155 160
Phe Thr Asp Ala Val Arg Ala Val Glu Ala Ala Ala Ser Phe Pro Arg
165 170 175
Val Asp His Glu Arg Ile Val Ile Ala Gly Gly Ser Gln Gly Gly Gly
180 185 190
Ile Ala Leu Ala Val Ser Ala Leu Ser Lys Lys Ala Lys Ala Leu Leu
195 200 205
Cys Asp Val Pro Phe Leu Cys His Phe Arg Arg Ala Val Gln Leu Val
210 215 220
Asp Thr His Pro Tyr Ala Glu Ile Thr Asn Phe Leu Lys Thr His Arg
225 230 235 240
Asp Lys Glu Glu Ile Val Phe Arg Thr Leu Ser Tyr Phe Asp Gly Val
245 250 255
Asn Phe Ala Val Arg Ala Lys Ile Pro Ala Leu Phe Ser Val Gly Leu
260 265 270
Met Asp Asn Ile Cys Pro Pro Ser Thr Val Phe Ala Ala Tyr Asn His
275 280 285
Tyr Ala Gly Pro Lys Glu Ile Arg Ile Tyr Pro Tyr Asn Asn His Glu
290 295 300
Gly Gly Gly Ser Phe Gln Ala Ile Glu Gln Val Lys Phe Leu Lys Arg
305 310 315 320
Leu Phe Glu Lys Gly
325
<210> 23
<211> 325
<212> PRT
<213> 栖热袍菌属菌种RQ2
<400> 23
Met Ala Phe Phe Asp Leu Pro Leu Glu Glu Leu Lys Lys Tyr Arg Pro
1 5 10 15
Glu Arg Tyr Glu Glu Lys Asp Phe Asp Glu Phe Trp Lys Glu Thr Leu
20 25 30
Ala Glu Ser Glu Lys Phe Pro Leu Asp Pro Val Phe Glu Arg Met Glu
35 40 45
Ser His Leu Lys Thr Val Glu Val Tyr Asp Val Thr Phe Ser Gly Tyr
50 55 60
Arg Gly Gln Arg Ile Lys Gly Trp Leu Leu Val Pro Lys Leu Glu Glu
65 70 75 80
Glu Lys Leu Pro Cys Val Val Gln Tyr Ile Gly Tyr Asn Gly Gly Arg
85 90 95
Gly Phe Pro His Asp Trp Leu Phe Trp Pro Ser Met Gly Tyr Ile Cys
100 105 110
Phe Val Met Asp Thr Arg Gly Gln Gly Ser Gly Trp Leu Lys Gly Asp
115 120 125
Thr Pro Asp Tyr Pro Glu Asp Pro Val Asp Pro Gln Tyr Pro Gly Phe
130 135 140
Met Thr Arg Gly Ile Leu Asp Pro Arg Thr Tyr Tyr Tyr Arg Arg Val
145 150 155 160
Phe Thr Asp Ala Val Arg Ala Val Glu Ala Ala Ala Ser Phe Pro Arg
165 170 175
Val Asp His Glu Arg Ile Val Ile Ala Gly Gly Ser Gln Gly Gly Gly
180 185 190
Ile Ala Leu Ala Val Ser Ala Leu Ser Lys Lys Ala Lys Ala Leu Leu
195 200 205
Cys Asp Val Pro Phe Leu Cys His Phe Arg Arg Ala Val Gln Leu Val
210 215 220
Asp Thr His Pro Tyr Ala Glu Ile Thr Asn Phe Leu Lys Thr His Arg
225 230 235 240
Asp Lys Glu Glu Ile Val Phe Arg Thr Leu Ser Tyr Phe Asp Gly Val
245 250 255
Asn Phe Ala Val Arg Ala Lys Ile Pro Ala Leu Phe Ser Val Gly Leu
260 265 270
Met Asp Asn Ile Cys Pro Pro Ser Thr Val Phe Ala Ala Tyr Asn His
275 280 285
Tyr Ala Gly Pro Lys Glu Ile Arg Ile Tyr Pro Tyr Asn Asn His Glu
290 295 300
Gly Gly Gly Ser Phe Gln Ala Ile Glu Gln Val Lys Phe Leu Lys Arg
305 310 315 320
Leu Phe Glu Lys Gly
325
<210> 24
<211> 329
<212> PRT
<213> 栖热袍菌属菌种RQ2
<400> 24
Met Ala Leu Phe Asp Met Pro Leu Glu Lys Leu Arg Ser Tyr Leu Pro
1 5 10 15
Asp Arg Tyr Glu Glu Glu Asp Phe Asp Leu Phe Trp Lys Glu Thr Leu
20 25 30
Glu Glu Ser Arg Lys Phe Pro Leu Asp Pro Ile Phe Glu Arg Val Asp
35 40 45
Tyr Leu Leu Glu Asn Val Glu Val Tyr Asp Val Thr Phe Ser Gly Tyr
50 55 60
Arg Gly Gln Arg Ile Lys Ala Trp Leu Ile Leu Pro Val Val Lys Lys
65 70 75 80
Glu Glu Arg Leu Pro Cys Ile Val Glu Phe Ile Gly Tyr Arg Gly Gly
85 90 95
Arg Gly Phe Pro Phe Asp Trp Leu Phe Trp Ser Ser Ala Gly Tyr Ala
100 105 110
His Phe Val Met Asp Thr Arg Gly Gln Gly Thr Ser Arg Val Lys Gly
115 120 125
Asp Thr Pro Asp Tyr Cys Asp Glu Pro Ile Asn Pro Gln Phe Pro Gly
130 135 140
Phe Met Thr Arg Gly Ile Leu Asp Pro Arg Thr Tyr Tyr Tyr Arg Arg
145 150 155 160
Val Phe Thr Asp Ala Val Arg Ala Val Glu Thr Ala Ser Ser Phe Pro
165 170 175
Gly Ile Asp Pro Glu Arg Ile Ala Val Val Gly Thr Ser Gln Gly Gly
180 185 190
Gly Ile Ala Leu Ala Val Ala Ala Leu Ser Glu Ile Pro Lys Ala Leu
195 200 205
Val Ser Asn Val Pro Phe Leu Cys His Phe Arg Arg Ala Val Gln Ile
210 215 220
Thr Asp Asn Ala Pro Tyr Ser Glu Ile Val Asn Tyr Leu Lys Val His
225 230 235 240
Arg Asp Lys Glu Glu Ile Val Phe Arg Thr Leu Ser Tyr Phe Asp Gly
245 250 255
Val Asn Phe Ala Ala Arg Ala Lys Ile Pro Ala Leu Phe Ser Val Ala
260 265 270
Leu Met Asp Lys Thr Cys Pro Pro Ser Thr Val Phe Ala Ala Tyr Asn
275 280 285
His Tyr Ala Gly Pro Lys Glu Ile Lys Val Tyr Pro Phe Asn Glu His
290 295 300
Glu Gly Gly Glu Ser Phe Gln Arg Met Glu Glu Leu Arg Phe Met Lys
305 310 315 320
Arg Ile Leu Lys Gly Glu Phe Lys Ala
325
<210> 25
<211> 320
<212> PRT
<213> 解糖热厌氧杆菌(Thermoanaerobacterium saccharolyticum)
<400> 25
Met Gly Leu Phe Asp Met Pro Leu Gln Lys Leu Arg Glu Tyr Thr Gly
1 5 10 15
Thr Asn Pro Cys Pro Glu Asp Phe Asp Glu Tyr Trp Asp Arg Ala Leu
20 25 30
Asp Glu Met Arg Ser Val Asp Pro Lys Ile Lys Met Lys Lys Ser Ser
35 40 45
Phe Gln Val Pro Phe Ala Glu Cys Tyr Asp Leu Tyr Phe Thr Gly Val
50 55 60
Arg Gly Ala Arg Ile His Ala Lys Tyr Ile Arg Pro Lys Thr Glu Gly
65 70 75 80
Lys His Pro Ala Leu Ile Arg Phe His Gly Tyr Ser Ser Asn Ser Gly
85 90 95
Asp Trp Asn Asp Lys Leu Asn Tyr Val Ala Ala Gly Phe Thr Val Val
100 105 110
Ala Met Asp Ala Arg Gly Gln Gly Gly Gln Ser Gln Asp Val Gly Gly
115 120 125
Val Asn Gly Asn Thr Leu Asn Gly His Ile Ile Arg Gly Leu Asp Asp
130 135 140
Asp Ala Asp Asn Met Leu Phe Arg His Ile Phe Leu Asp Thr Ala Gln
145 150 155 160
Leu Ala Gly Ile Val Met Asn Met Pro Glu Ile Asp Glu Asp Arg Val
165 170 175
Ala Val Met Gly Pro Ser Gln Gly Gly Gly Leu Ser Leu Ala Cys Ala
180 185 190
Ala Leu Glu Pro Lys Ile Arg Lys Val Val Ser Glu Tyr Pro Phe Leu
195 200 205
Ser Asp Tyr Lys Arg Val Trp Asp Leu Asp Leu Ala Lys Asn Ala Tyr
210 215 220
Gln Glu Ile Thr Asp Tyr Phe Arg Leu Phe Asp Pro Arg His Glu Arg
225 230 235 240
Glu Asn Glu Val Phe Thr Lys Leu Gly Tyr Ile Asp Val Lys Asn Leu
245 250 255
Ala Lys Arg Ile Lys Gly Asp Val Leu Met Cys Val Gly Leu Met Asp
260 265 270
Gln Val Cys Pro Pro Ser Thr Val Phe Ala Ala Tyr Asn Asn Ile Gln
275 280 285
Ser Lys Lys Asp Ile Lys Val Tyr Pro Asp Tyr Gly His Glu Pro Met
290 295 300
Arg Gly Phe Gly Asp Leu Ala Met Gln Phe Met Leu Glu Leu Tyr Ser
305 310 315 320
<210> 26
<211> 312
<212> PRT
<213> 乳酸乳球菌(Lactococcus lactis)
<400> 26
Met Thr Lys Ile Asn Asn Trp Gln Asp Tyr Gln Gly Ser Ser Leu Lys
1 5 10 15
Pro Glu Asp Phe Asp Lys Phe Trp Asp Glu Lys Ile Asn Leu Val Ser
20 25 30
Asn His Gln Phe Glu Phe Glu Leu Ile Glu Lys Asn Leu Ser Ser Lys
35 40 45
Val Val Asn Phe Tyr His Leu Trp Phe Thr Ala Ile Asp Gly Ala Lys
50 55 60
Ile His Ala Gln Leu Ile Val Pro Lys Asn Leu Lys Glu Lys Tyr Pro
65 70 75 80
Ala Ile Leu Gln Phe His Gly Tyr His Cys Asp Ser Gly Asp Trp Val
85 90 95
Asp Lys Ile Gly Ile Val Ala Glu Gly Asn Val Val Leu Ala Leu Asp
100 105 110
Cys Arg Gly Gln Gly Gly Leu Ser Gln Asp Asn Ile Gln Thr Met Gly
115 120 125
Met Thr Met Lys Gly Leu Ile Val Arg Gly Ile Asp Glu Gly Tyr Glu
130 135 140
Asn Leu Tyr Tyr Val Arg Gln Phe Met Asp Leu Ile Thr Ala Thr Lys
145 150 155 160
Ile Leu Ser Glu Phe Asp Phe Val Asp Glu Thr Asn Ile Ser Ala Gln
165 170 175
Gly Ala Ser Gln Gly Gly Ala Leu Ala Val Ala Cys Ala Ala Leu Ser
180 185 190
Pro Leu Ile Lys Lys Val Thr Ala Thr Tyr Pro Phe Leu Ser Asp Tyr
195 200 205
Arg Lys Ala Tyr Glu Leu Gly Ala Glu Glu Ser Ala Phe Glu Glu Leu
210 215 220
Pro Tyr Trp Phe Gln Phe Lys Asp Pro Leu His Leu Arg Glu Asp Trp
225 230 235 240
Phe Phe Asn Gln Leu Glu Tyr Ile Asp Ile Gln Asn Leu Ala Pro Arg
245 250 255
Ile Lys Ala Glu Val Ile Trp Ile Leu Gly Gly Lys Asp Thr Val Val
260 265 270
Pro Pro Ile Thr Gln Met Ala Ala Tyr Asn Lys Ile Gln Ser Lys Lys
275 280 285
Ser Leu Tyr Val Leu Pro Glu Tyr Gly His Glu Tyr Leu Pro Lys Ile
290 295 300
Ser Asp Trp Leu Arg Glu Asn Gln
305 310
<210> 27
<211> 323
<212> PRT
<213> 百脉根中间根瘤菌(Mesorhizobium loit)
<400> 27
Met Pro Phe Pro Asp Leu Ile Gln Pro Glu Leu Gly Ala Tyr Val Ser
1 5 10 15
Ser Val Gly Met Pro Asp Asp Phe Ala Gln Phe Trp Thr Ser Thr Ile
20 25 30
Ala Glu Ala Arg Gln Ala Gly Gly Glu Val Ser Ile Val Gln Ala Gln
35 40 45
Thr Thr Leu Lys Ala Val Gln Ser Phe Asp Val Thr Phe Pro Gly Tyr
50 55 60
Gly Gly His Pro Ile Lys Gly Trp Leu Ile Leu Pro Thr His His Lys
65 70 75 80
Gly Arg Leu Pro Leu Val Val Gln Tyr Ile Gly Tyr Gly Gly Gly Arg
85 90 95
Gly Leu Ala His Glu Gln Leu His Trp Ala Ala Ser Gly Phe Ala Tyr
100 105 110
Phe Arg Met Asp Thr Arg Gly Gln Gly Ser Asp Trp Ser Val Gly Glu
115 120 125
Thr Ala Asp Pro Val Gly Ser Thr Ser Ser Ile Pro Gly Phe Met Thr
130 135 140
Arg Gly Val Leu Asp Lys Asn Asp Tyr Tyr Tyr Arg Arg Leu Phe Thr
145 150 155 160
Asp Ala Val Arg Ala Ile Asp Ala Leu Leu Gly Leu Asp Phe Val Asp
165 170 175
Pro Glu Arg Ile Ala Val Cys Gly Asp Ser Gln Gly Gly Gly Ile Ser
180 185 190
Leu Ala Val Gly Gly Ile Asp Pro Arg Val Lys Ala Val Met Pro Asp
195 200 205
Val Pro Phe Leu Cys Asp Phe Pro Arg Ala Val Gln Thr Ala Val Arg
210 215 220
Asp Pro Tyr Leu Glu Ile Val Arg Phe Leu Ala Gln His Arg Glu Lys
225 230 235 240
Lys Ala Ala Val Phe Glu Thr Leu Asn Tyr Phe Asp Cys Val Asn Phe
245 250 255
Ala Arg Arg Ser Lys Ala Pro Ala Leu Phe Ser Val Ala Leu Met Asp
260 265 270
Glu Val Cys Pro Pro Ser Thr Val Tyr Gly Ala Phe Asn Ala Tyr Ala
275 280 285
Gly Glu Lys Thr Ile Thr Glu Tyr Glu Phe Asn Asn His Glu Gly Gly
290 295 300
Gln Gly Tyr Gln Glu Arg Gln Gln Met Thr Trp Leu Ser Arg Leu Phe
305 310 315 320
Gly Val Gly
<210> 28
<211> 329
<212> PRT
<213> 嗜热脂肪土芽孢杆菌(Geobacillus stearothermophilus)
<400> 28
Met Phe Asp Met Pro Leu Ala Gln Leu Gln Lys Tyr Met Gly Thr Asn
1 5 10 15
Pro Lys Pro Ala Asp Phe Ala Asp Phe Trp Ser Arg Ala Leu Glu Glu
20 25 30
Leu Ser Ala Gln Ser Leu His Tyr Glu Leu Ile Pro Ala Thr Phe Gln
35 40 45
Thr Thr Val Ala Ser Cys Tyr His Leu Tyr Phe Thr Gly Val Gly Gly
50 55 60
Ala Arg Val His Cys Gln Leu Val Lys Pro Arg Glu Gln Lys Gln Lys
65 70 75 80
Gly Pro Gly Leu Val Trp Phe His Gly Tyr His Thr Asn Ser Gly Asp
85 90 95
Trp Val Asp Lys Leu Ala Tyr Ala Ala Ala Gly Phe Thr Val Leu Ala
100 105 110
Met Asp Cys Arg Gly Gln Gly Gly Lys Ser Glu Asp Asn Leu Gln Val
115 120 125
Lys Gly Pro Thr Leu Lys Gly His Ile Ile Arg Gly Ile Glu Asp Pro
130 135 140
Asn Pro His His Leu Tyr Tyr Arg Asn Val Phe Leu Asp Thr Val Gln
145 150 155 160
Ala Val Arg Ile Leu Cys Ser Met Asp His Ile Asp Arg Glu Arg Ile
165 170 175
Gly Val Tyr Gly Ala Ser Gln Gly Gly Ala Leu Ala Leu Ala Cys Ala
180 185 190
Ala Leu Glu Pro Ser Val Val Lys Lys Ala Val Val Leu Tyr Pro Phe
195 200 205
Leu Ser Asp Tyr Lys Arg Ala Gln Glu Leu Asp Met Lys Asn Thr Ala
210 215 220
Tyr Glu Glu Ile His Tyr Tyr Phe Arg Phe Leu Asp Pro Thr His Glu
225 230 235 240
Arg Glu Glu Glu Val Phe Tyr Lys Leu Gly Tyr Ile Asp Ile Gln Leu
245 250 255
Leu Ala Asp Arg Ile Cys Ala Asp Val Leu Trp Ala Val Ala Leu Glu
260 265 270
Asp His Ile Cys Pro Pro Ser Thr Gln Phe Ala Val Tyr Asn Lys Ile
275 280 285
Lys Ser Lys Lys Asp Met Val Leu Phe Tyr Glu Tyr Gly His Glu Tyr
290 295 300
Leu Pro Thr Met Gly Asp Arg Ala Tyr Leu Phe Phe Cys Pro Ile Phe
305 310 315 320
Phe Pro Ile Gln Lys Arg Asn Val Lys
325
<210> 29
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 29
Ala His Pro Glu Ser Leu Gly Ile Lys Tyr Ala Leu Asp Gly Asn Ser
1 5 10 15
Asp Pro His Ala
20
<210> 30
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 30
Ala Ser Val Ser Asn Tyr Pro Pro Ile His His Leu Ala Thr Ser Asn
1 5 10 15
Thr Thr Val Asn
20
<210> 31
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 31
Asp Glu Cys Met Glu Pro Leu Asn Ala Ala His Cys Trp Arg
1 5 10
<210> 32
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 32
Asp Glu Cys Met His Gly Ser Asp Val Glu Phe Cys Thr Ser
1 5 10
<210> 33
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 33
Asp Leu Cys Ser Met Gln Met Met Asn Thr Gly Cys His Tyr
1 5 10
<210> 34
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 34
Asp Leu Cys Ser Ser Pro Ser Thr Trp Gly Ser Cys Ile Arg
1 5 10
<210> 35
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 35
Asp Pro Asn Glu Ser Asn Tyr Glu Asn Ala Thr Thr Val Ser Gln Pro
1 5 10 15
Thr Arg His Leu
20
<210> 36
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 36
Glu Pro Thr His Pro Thr Met Arg Ala Gln Met His Gln Ser Leu Arg
1 5 10 15
Ser Ser Ser Pro
20
<210> 37
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 37
Gly Asn Thr Asp Thr Thr Pro Pro Asn Ala Val Met Glu Pro Thr Val
1 5 10 15
Gln His Lys Trp
20
<210> 38
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 38
Asn Gly Pro Asp Met Val Gln Ser Val Gly Lys His Lys Asn Ser
1 5 10 15
<210> 39
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 39
Asn Gly Pro Glu Val Arg Gln Ile Pro Ala Asn Phe Glu Lys Leu
1 5 10 15
<210> 40
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 40
Asn Asn Thr Ser Ala Asp Asn Pro Pro Glu Thr Asp Ser Lys His His
1 5 10 15
Leu Ser Met Ser
20
<210> 41
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 41
Asn Asn Thr Trp Pro Glu Gly Ala Gly His Thr Met Pro Ser Thr Asn
1 5 10 15
Ile Arg Gln Ala
20
<210> 42
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 42
Asn Pro Thr Ala Thr Pro His Met Lys Asp Pro Met His Ser Asn Ala
1 5 10 15
His Ser Ser Ala
20
<210> 43
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 43
Asn Pro Thr Asp His Ile Pro Ala Asn Ser Thr Asn Ser Arg Val Ser
1 5 10 15
Lys Gly Asn Thr
20
<210> 44
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 44
Asn Pro Thr Asp Ser Thr His Met Met His Ala Arg Asn His Glu
1 5 10 15
<210> 45
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 45
Gln His Cys Ile Thr Glu Arg Leu His Pro Pro Cys Thr Lys
1 5 10
<210> 46
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 46
Thr Pro Cys Ala Pro Ala Ser Phe Asn Pro His Cys Ser Arg
1 5 10
<210> 47
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 47
Thr Pro Cys Ala Thr Tyr Pro His Phe Ser Gly Cys Arg Ala
1 5 10
<210> 48
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 48
Trp Cys Thr Asp Phe Cys Thr Arg Ser Thr Pro Thr Ser Thr Ser Arg
1 5 10 15
Ser Thr Thr Ser
20
<210> 49
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 49
Ala Pro Pro Leu Lys Thr Tyr Met Gln Glu Arg Glu Leu Thr Met Ser
1 5 10 15
Gln Asn Lys Asp
20
<210> 50
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 50
Glu Pro Pro Thr Arg Thr Arg Val Asn Asn His Thr Val Thr Val Gln
1 5 10 15
Ala Gln Gln His
20
<210> 51
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 51
Gly Tyr Cys Leu Arg Gly Asp Glu Pro Ala Val Cys Ser Gly
1 5 10
<210> 52
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 52
Leu Ser Ser Lys Asp Phe Gly Val Thr Asn Thr Asp Gln Arg Thr Tyr
1 5 10 15
Asp Tyr Thr Thr
20
<210> 53
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 53
Asn Phe Cys Glu Thr Gln Leu Asp Leu Ser Val Cys Thr Val
1 5 10
<210> 54
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 54
Asn Thr Cys Gln Pro Thr Lys Asn Ala Thr Pro Cys Ser Ala
1 5 10
<210> 55
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 55
Pro Ser Glu Pro Glu Arg Arg Asp Arg Asn Ile Ala Ala Asn Ala Gly
1 5 10 15
Arg Phe Asn Thr
20
<210> 56
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 56
Thr His Asn Met Ser His Phe Pro Pro Ser Gly His Pro Lys Arg Thr
1 5 10 15
Ala Thr
<210> 57
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 57
Thr Thr Cys Pro Thr Met Gly Thr Tyr His Val Cys Trp Leu
1 5 10
<210> 58
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 58
Tyr Cys Ala Asp His Thr Pro Asp Pro Ala Asn Pro Asn Lys Ile Cys
1 5 10 15
Gly Tyr Ser His
20
<210> 59
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 59
Ala Ala Asn Pro His Thr Glu Trp Asp Arg Asp Ala Phe Gln Leu Ala
1 5 10 15
Met Pro Pro Lys
20
<210> 60
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 60
Asp Leu His Pro Met Asp Pro Ser Asn Lys Arg Pro Asp Asn Pro Ser
1 5 10 15
Asp Leu His Thr
20
<210> 61
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 61
Glu Ser Cys Val Ser Asn Ala Leu Met Asn Gln Cys Ile Tyr
1 5 10
<210> 62
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 62
His Asn Lys Ala Asp Ser Trp Asp Pro Asp Leu Pro Pro His Ala Gly
1 5 10 15
Met Ser Leu Gly
20
<210> 63
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 63
Leu Asn Asp Gln Arg Lys Pro Gly Pro Pro Thr Met Pro Thr His Ser
1 5 10 15
Pro Ala Val Gly
20
<210> 64
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 64
Asn Thr Cys Ala Thr Ser Pro Asn Ser Tyr Thr Cys Ser Asn
1 5 10
<210> 65
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 65
Ser Asp Cys Thr Ala Gly Leu Val Pro Pro Leu Cys Ala Thr
1 5 10
<210> 66
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 66
Thr Ile Glu Ser Ser Gln His Ser Arg Thr His Gln Gln Asn Tyr Gly
1 5 10 15
Ser Thr Lys Thr
20
<210> 67
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 67
Val Gly Thr Met Lys Gln His Pro Thr Thr Thr Gln Pro Pro Arg Val
1 5 10 15
Ser Ala Thr Asn
20
<210> 68
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 68
Tyr Ser Glu Thr Pro Asn Asp Gln Lys Pro Asn Pro His Tyr Lys Val
1 5 10 15
Ser Gly Thr Lys
20
<210> 69
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 69
Asn Gly Asn Asn His Thr Asp Ile Pro Asn Arg Ser Ser Tyr Thr Gly
1 5 10 15
Gly Ser Phe Ala
20
<210> 70
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 70
Thr Met Thr Asn His Val Tyr Asn Ser Tyr Thr Glu Lys His Ser Ser
1 5 10 15
Thr His Arg Ser
20
<210> 71
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 71
Thr Thr Tyr His Tyr Lys Asn Ile Tyr Gln Glu Ser Tyr Gln Gln Arg
1 5 10 15
Asn Pro Ala Val
20
<210> 72
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 72
Val Glu Pro Ala Thr Lys Asn Met Arg Glu Ala Arg Ser Ser Thr Gln
1 5 10 15
Met Arg Arg Ile
20
<210> 73
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 73
Tyr Leu Leu Pro Lys Asp Gln Thr Thr Ala Pro Gln Val Thr Pro Ile
1 5 10 15
Val Gln His Lys
20
<210> 74
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 74
Ala Ser Asn Leu Asp Ser Thr Phe Thr Ala Ile Asn Thr Pro Ala Cys
1 5 10 15
Cys Thr
<210> 75
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 75
Glu Phe Pro Tyr Tyr Asn Asp Asn Pro Pro Asn Pro Glu Arg His Thr
1 5 10 15
Leu Arg
<210> 76
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 76
Gly Met Pro Thr Arg Tyr Tyr His Asn Thr Pro Pro His Leu Thr Pro
1 5 10 15
Lys Phe
<210> 77
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 77
His Lys Asn Ala Ile Gln Pro Val Asn Asp Ala Thr Thr Leu Asp Thr
1 5 10 15
Thr Met
<210> 78
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 78
Ala Val Val Pro Ala Asp Leu Asn Asp His Ala Asn His Leu Ser
1 5 10 15
<210> 79
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 79
Asp Leu Gly Thr Phe Pro Asn Arg Thr Leu Lys Met Ala Ala His
1 5 10 15
<210> 80
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 80
Phe Asp Gly Ile Gly Leu Gly Thr Ala Thr Arg His Gln Asn Arg
1 5 10 15
<210> 81
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 81
Gln Ala Ala Gln Val His Met Met Gln His Ser Arg Pro Thr Thr
1 5 10 15
<210> 82
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 82
Ser Glu Ala Arg Ala Arg Thr Phe Asn Asp His Thr Thr Pro Met Pro
1 5 10 15
Ile Ile
<210> 83
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 83
Glu Leu Asp His Asp Ser Arg His Tyr Met Asn Gly Leu Gln Arg Lys
1 5 10 15
Val Thr
<210> 84
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 84
Gly Pro Gln His Val Leu Met Gln Asp Thr His Gln Gly Tyr Ala Phe
1 5 10 15
Asp Asn
<210> 85
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 85
Thr Thr Gly Ser Ser Ser Gln Ala Asp Thr Ser Ala Ser Met Ser Ile
1 5 10 15
Val Pro Ala His
20
<210> 86
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 86
Lys Ala Pro Ile Ala Asn Met Leu Gln Pro His Ser Tyr Gln Tyr Ser
1 5 10 15
Val Ala
<210> 87
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 87
Thr Tyr Gln Gly Val Pro Ser Trp Pro Ala Val Ile Asp Asp Ala Ile
1 5 10 15
Arg Arg
<210> 88
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 88
Val Asn Pro Asn Trp Val Glu Thr Gln Ala Leu His Gln Pro Pro Gly
1 5 10 15
Asn Thr
<210> 89
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 89
Asp His Asn Asn Arg Gln His Ala Val Glu Val Arg Glu Asn Lys Thr
1 5 10 15
His Thr Ala Arg
20
<210> 90
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 90
Ile Tyr Pro Asn Glu Ser Met Ser Thr Ser Asn Val Arg Gly Pro Tyr
1 5 10 15
His Pro
<210> 91
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 91
His Asp Pro Asn His Leu Thr His Gln Ala Arg Thr Ile Tyr Arg Asn
1 5 10 15
Ala Asn His Thr
20
<210> 92
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 92
Ser Asn Ala Thr Met Tyr Asn Ile Gln Ser His Ser His His Gln
1 5 10 15
<210> 93
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 93
Ala Asn Glu Leu Ser Thr Tyr Ala Gln Thr Asn Pro Gly Ser Gly
1 5 10 15
<210> 94
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 94
Asp Thr Ile His Pro Asn Lys Met Lys Ser Pro Ser Ser Pro Leu
1 5 10 15
<210> 95
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 95
Ala Pro Pro Thr Tyr Gln Thr Ala Ser Tyr Pro His Asn Leu Pro Ser
1 5 10 15
Lys Arg Lys Met
20
<210> 96
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 96
Gln Val Pro Asp Tyr Leu Ser Pro Thr His Gln Lys Lys Ala Phe Leu
1 5 10 15
Glu Ile Pro Thr
20
<210> 97
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 97
Thr Asn Asp Leu His Ala Asn Pro Phe Thr Gly Thr Tyr Ile Ala Pro
1 5 10 15
Asp Pro Thr Ser
20
<210> 98
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 98
His Lys Asn Glu Asn Ile Met Gln Tyr Asn Val Asn Asp Arg Trp His
1 5 10 15
Ile Thr Pro Ala
20
<210> 99
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 99
Ile Asp Gly Pro His His Ser Pro Val His Arg Tyr His Thr Pro Ser
1 5 10 15
Ile Thr
<210> 100
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 100
Ala Ile Glu Tyr Gln His Ser Ala Thr Thr Pro Trp Thr Met Arg Thr
1 5 10 15
Arg Leu Pro Pro
20
<210> 101
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 101
Glu Phe Tyr Pro Phe Ala Glu Val Pro Pro Glu Lys Ser Gly Ile Gly
1 5 10 15
Arg Gln Val Phe
20
<210> 102
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 102
Gly Val His Gln Tyr Ser Arg Pro Thr Val Pro Ser Tyr Leu Trp Thr
1 5 10 15
Ser Gly Gln His
20
<210> 103
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 103
Gly Tyr Gln Pro His Tyr Val Asp His Thr Ile Gly Trp Gln Pro Met
1 5 10 15
Ile Arg Pro Asn
20
<210> 104
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 104
Gln Phe Asn Gln Thr Ser His Ser Phe Met His Gly Thr Ser Gly Tyr
1 5 10 15
Val Pro Gly Lys
20
<210> 105
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 105
Ser Phe Ser Trp His Arg Gly Asp Trp Glu Leu Gly His Gln Ser Lys
1 5 10 15
Thr Met Gly Met
20
<210> 106
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 106
Ser Met Trp His Asp Ile Thr Lys Arg Tyr Arg Asn Pro Ser Glu Met
1 5 10 15
Val Ser Ala Tyr
20
<210> 107
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 107
Thr His Gly Asn Lys His Gln Ser Trp Thr Tyr Pro Ser Glu Ile Asn
1 5 10 15
His Lys Asn Tyr
20
<210> 108
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 108
Trp His Glu Pro His Gln Phe Ser Gly Glu Asn Thr Asp Tyr Ser Ser
1 5 10 15
Ser Met Gly Thr
20
<210> 109
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 109
Thr His Gly Asn Lys His Gln Ser Trp Thr Tyr Pro Ser Glu Ile Asn
1 5 10 15
His Lys Asn Tyr
20
<210> 110
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 110
Asp Gly Tyr Lys Leu Gln Thr Ser Leu Asp Trp Gln Met Trp Asn Pro
1 5 10 15
<210> 111
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 111
Phe Pro Ser Lys Trp Tyr Asn His His Arg His Ile Thr Gly His Val
1 5 10 15
<210> 112
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 112
Gly Gly Met Gly Ala Leu Glu Ser Tyr Arg Gln Trp Asn His Leu Ala
1 5 10 15
<210> 113
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 113
Gly Ile Asn Lys Gly Gln Arg Pro Pro Trp Glu Ser Trp His Glu Asn
1 5 10 15
<210> 114
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 114
Gly Tyr Gly Gln Tyr Val Ser Gln Gln Thr Trp Ala His Ser Asn Lys
1 5 10 15
<210> 115
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 115
His Asp His Leu Ser Trp Trp Gly Gln Phe Asp Arg Gln Asn Leu Leu
1 5 10 15
<210> 116
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 116
Met Pro Gly His Gln Glu Ser Ile Lys Val Gln Asn Trp Asn Arg Val
1 5 10 15
<210> 117
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 117
Asn Leu His Ser Pro Trp Pro Ser His Ala Ala His His Trp Ser Thr
1 5 10 15
<210> 118
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 118
Asn Gln Gln Met Lys Leu Val Pro Gln His Trp His Arg Ala Gln Pro
1 5 10 15
<210> 119
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> 合成口腔表面结合肽
<400> 119
Ser Glu Lys Trp Phe Asn Pro Gly Pro Trp Pro Lys Leu Ala Thr Gln
1 5 10 15
<210> 120
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 120
Ser Ser Arg Pro Asn Gly Asn Asn His Thr Asp Ile Pro Asn Arg Ser
1 5 10 15
Ser Tyr Thr Gly Gly Ser Phe Ala Lys
20 25
<210> 121
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 121
Ser Ser Arg Pro Thr Met Thr Asn His Val Tyr Asn Ser Tyr Thr Glu
1 5 10 15
Lys His Ser Ser Thr His Arg Ser Lys
20 25
<210> 122
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 122
Ser Ser Arg Pro Thr Thr Tyr His Tyr Lys Asn Ile Tyr Gln Glu Ser
1 5 10 15
Tyr Gln Gln Arg Asn Pro Ala Val Lys
20 25
<210> 123
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 123
Ser Ser Arg Pro Val Glu Pro Ala Thr Lys Asn Met Arg Glu Ala Arg
1 5 10 15
Ser Ser Thr Gln Met Arg Arg Ile Lys
20 25
<210> 124
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 124
Ser Ser Arg Pro Tyr Leu Leu Pro Lys Asp Gln Thr Thr Ala Pro Gln
1 5 10 15
Val Thr Pro Ile Val Gln His Lys Lys
20 25
<210> 125
<211> 23
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 125
Ser Ser Arg Pro Glu Phe Pro Tyr Tyr Asn Asp Asn Pro Pro Asn Pro
1 5 10 15
Glu Arg His Thr Leu Arg Lys
20
<210> 126
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 126
Ser Ser Arg Pro Asp Leu Gly Thr Phe Pro Asn Arg Thr Leu Lys Met
1 5 10 15
Ala Ala His Lys
20
<210> 127
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 127
Ser Ser Arg Pro Phe Asp Gly Ile Gly Leu Gly Thr Ala Thr Arg His
1 5 10 15
Gln Asn Arg Lys
20
<210> 128
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 128
Ser Ser Arg Pro Gln Ala Ala Gln Val His Met Met Gln His Ser Arg
1 5 10 15
Pro Thr Thr Lys
20
<210> 129
<211> 23
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 129
Ser Ser Arg Pro Ser Glu Ala Arg Ala Arg Thr Phe Asn Asp His Thr
1 5 10 15
Thr Pro Met Pro Ile Ile Lys
20
<210> 130
<211> 23
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 130
Ser Ser Arg Pro Glu Leu Asp His Asp Ser Arg His Tyr Met Asn Gly
1 5 10 15
Leu Gln Arg Lys Val Thr Lys
20
<210> 131
<211> 23
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 131
Ser Ser Arg Pro Gly Pro Gln His Val Leu Met Gln Asp Thr His Gln
1 5 10 15
Gly Tyr Ala Phe Asp Asn Lys
20
<210> 132
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 132
Ser Ser Arg Pro Thr Thr Gly Ser Ser Ser Gln Ala Asp Thr Ser Ala
1 5 10 15
Ser Met Ser Ile Val Pro Ala His Lys
20 25
<210> 133
<211> 23
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 133
Ser Ser Arg Pro Thr Tyr Gln Gly Val Pro Ser Trp Pro Ala Val Ile
1 5 10 15
Asp Asp Ala Ile Arg Arg Lys
20
<210> 134
<211> 23
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 134
Ser Ser Arg Pro Val Asn Pro Asn Trp Val Glu Thr Gln Ala Leu His
1 5 10 15
Gln Pro Pro Gly Asn Thr Lys
20
<210> 135
<211> 23
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 135
Ser Ser Arg Pro Ile Tyr Pro Asn Glu Ser Met Ser Thr Ser Asn Val
1 5 10 15
Arg Gly Pro Tyr His Pro Lys
20
<210> 136
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 136
Ser Ser Arg Pro His Asp Pro Asn His Leu Thr His Gln Ala Arg Thr
1 5 10 15
Ile Tyr Arg Asn Ala Asn His Thr Lys
20 25
<210> 137
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 137
Ser Ser Arg Pro Ala Pro Pro Thr Tyr Gln Thr Ala Ser Tyr Pro His
1 5 10 15
Asn Leu Pro Ser Lys Arg Lys Met Lys
20 25
<210> 138
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 138
Ser Ser Arg Pro Gln Val Pro Asp Tyr Leu Ser Pro Thr His Gln Lys
1 5 10 15
Lys Ala Phe Leu Glu Ile Pro Thr Lys
20 25
<210> 139
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 139
Ser Ser Arg Pro His Lys Asn Glu Asn Ile Met Gln Tyr Asn Val Asn
1 5 10 15
Asp Arg Trp His Ile Thr Pro Ala Lys
20 25
<210> 140
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 140
Ser Asn Ala Thr Met Tyr Asn Ile Gln Ser His Ser His His Gln
1 5 10 15
<210> 141
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 141
Gln Ala Ala Gln Val His Met Met Gln His Ser Arg Pro Thr Thr
1 5 10 15
<210> 142
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 142
His Asp Pro Tyr Thr Met Lys Ser Ala Leu Arg Gln Ser Thr Ser
1 5 10 15
<210> 143
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 143
Asp Leu Gly Thr Phe Pro Asn Arg Thr Leu Lys Met Ala Ala His
1 5 10 15
<210> 144
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 144
Asp Thr Ile His Pro Asn Lys Met Lys Ser Pro Ser Ser Pro Leu
1 5 10 15
<210> 145
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 145
Gly Ser Asn Asn His Leu Pro Ser Thr Val Pro Arg Leu Thr Val
1 5 10 15
<210> 146
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 146
Ser Asn Pro Ile Pro Asn Phe Ala His Asp Leu Arg His Ser Lys Tyr
1 5 10 15
Asn Ser
<210> 147
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 147
Thr Lys Pro Pro Arg Thr Pro Thr Ala Asn Thr Ser Arg Pro His His
1 5 10 15
Asn Phe
<210> 148
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 148
Ala Asn Ser Gly Phe Pro Ile Trp Leu Gln Lys Tyr Pro Trp Ser Glu
1 5 10 15
Val Gln Gln Glu
20
<210> 149
<211> 19
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 149
Ala Thr Pro Arg Leu Thr Pro Glu Ala His His Lys Ala Gly Asn Trp
1 5 10 15
Tyr Ala Ser
<210> 150
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 150
Ala Thr Pro Ser Gln His Arg Tyr Gly Leu Met Gln Asn His Ala Pro
1 5 10 15
Asn Gly Ile Glu
20
<210> 151
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 151
Gly Met Gly Ser Glu Val Leu Ser Gln Tyr Pro Gln Ala Pro Val Gly
1 5 10 15
<210> 152
<211> 21
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 152
Thr Thr Tyr His Tyr Lys Asn Ile Tyr Gln Glu Ser Tyr Gln Gln Arg
1 5 10 15
Asn Pro Ala Val Lys
20
<210> 153
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 153
Ser Asn Ala Thr Met Tyr Asn Ile Gln Ser His Ser His His Gln Lys
1 5 10 15
<210> 154
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 154
Gln Ala Ala Gln Val His Met Met Gln His Ser Arg Pro Thr Thr Lys
1 5 10 15
<210> 155
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 155
His Asp Pro Tyr Thr Met Lys Ser Ala Leu Arg Gln Ser Thr Ser Lys
1 5 10 15
<210> 156
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 156
Asp Leu Gly Thr Phe Pro Asn Arg Thr Leu Lys Met Ala Ala His Lys
1 5 10 15
<210> 157
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 157
Asp Thr Ile His Pro Asn Lys Met Lys Ser Pro Ser Ser Pro Leu Lys
1 5 10 15
<210> 158
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 158
Gly Ser Asn Asn His Leu Pro Ser Thr Val Pro Arg Leu Thr Val Lys
1 5 10 15
<210> 159
<211> 19
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 159
Ser Asn Pro Ile Pro Asn Phe Ala His Asp Leu Arg His Ser Lys Tyr
1 5 10 15
Asn Ser Lys
<210> 160
<211> 19
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 160
Thr Lys Pro Pro Arg Thr Pro Thr Ala Asn Thr Ser Arg Pro His His
1 5 10 15
Asn Phe Lys
<210> 161
<211> 21
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 161
Ala Asn Ser Gly Phe Pro Ile Trp Leu Gln Lys Tyr Pro Trp Ser Glu
1 5 10 15
Val Gln Gln Glu Lys
20
<210> 162
<211> 21
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 162
Ala Thr Pro Ser Gln His Arg Tyr Gly Leu Met Gln Asn His Ala Pro
1 5 10 15
Asn Gly Ile Glu Lys
20
<210> 163
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 163
Gly Met Gly Ser Glu Val Leu Ser Gln Tyr Pro Gln Ala Pro Val Gly
1 5 10 15
Lys
<210> 164
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体 - caspace 3可切割接头
<400> 164
Leu Glu Ser Gly Asp Glu Val Asp
1 5
<210> 165
<211> 37
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 165
Thr Ser Thr Ser Lys Ala Ser Thr Thr Thr Thr Ser Ser Lys Thr Thr
1 5 10 15
Thr Thr Ser Ser Lys Thr Thr Thr Thr Thr Ser Lys Thr Ser Thr Thr
20 25 30
Ser Ser Ser Ser Thr
35
<210> 166
<211> 22
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 166
Gly Gln Gly Gly Tyr Gly Gly Leu Gly Ser Gln Gly Ala Gly Arg Gly
1 5 10 15
Gly Leu Gly Gly Gln Gly
20
<210> 167
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 167
Gly Pro Gly Gly Tyr Gly Pro Gly Gln Gln
1 5 10
<210> 168
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 168
Gly Gly Ser Gly Pro Gly Ser Gly Gly
1 5
<210> 169
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 169
Gly Gly Pro Lys Lys
1 5
<210> 170
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 170
Gly Pro Gly Val Gly
1 5
<210> 171
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 171
Gly Gly Gly Cys Gly Gly Gly
1 5
<210> 172
<211> 4
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 172
Gly Gly Gly Cys
1
<210> 173
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 173
Pro His Met Ala Ser Met Thr Gly Gly Gln Gln Met Gly Ser
1 5 10
<210> 174
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 174
Gly Pro Glu Glu Ala Ala Lys Lys Glu Glu Ala Ala Lys Lys Pro Ala
1 5 10 15
<210> 175
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 175
Gly Ser Gly Gly Gly Gly Ser Gly Ser Gly Gly Gly Gly Ser
1 5 10
<210> 176
<211> 37
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 176
Gly Pro Glu Pro Glu Pro Glu Pro Glu Pro Ile Pro Glu Pro Pro Lys
1 5 10 15
Glu Ala Pro Val Val Ile Glu Lys Pro Lys Pro Lys Pro Lys Pro Lys
20 25 30
Pro Lys Pro Pro Ala
35
<210> 177
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 177
Gly Pro Gly Ser Gly Gly Ala Gly Ser Pro Gly Ser Ala Gly Gly Pro
1 5 10 15
Gly Ser
<210> 178
<211> 431
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 178
Met Ala Phe Phe Asp Leu Pro Leu Glu Glu Leu Lys Lys Tyr Arg Pro
1 5 10 15
Glu Arg Tyr Glu Glu Lys Asp Phe Asp Glu Phe Trp Glu Glu Thr Leu
20 25 30
Ala Glu Ser Glu Lys Phe Pro Leu Asp Pro Val Phe Glu Arg Met Glu
35 40 45
Ser His Leu Lys Thr Val Glu Ala Tyr Asp Val Thr Phe Ser Gly Tyr
50 55 60
Arg Gly Gln Arg Ile Lys Gly Trp Leu Leu Val Pro Lys Leu Glu Glu
65 70 75 80
Glu Lys Leu Pro Cys Val Val Gln Tyr Ile Gly Tyr Asn Gly Gly Arg
85 90 95
Gly Phe Pro His Asp Trp Leu Phe Trp Pro Ser Met Gly Tyr Ile Cys
100 105 110
Phe Val Met Asp Thr Arg Gly Gln Gly Ser Gly Trp Leu Lys Gly Asp
115 120 125
Thr Pro Asp Tyr Pro Glu Gly Pro Val Asp Pro Gln Tyr Pro Gly Phe
130 135 140
Met Thr Arg Gly Ile Leu Asp Pro Arg Thr Tyr Tyr Tyr Arg Arg Val
145 150 155 160
Phe Thr Asp Ala Val Arg Ala Val Glu Ala Ala Ala Ser Phe Pro Gln
165 170 175
Val Asp Gln Glu Arg Ile Val Ile Ala Gly Gly Ser Gln Gly Gly Gly
180 185 190
Ile Ala Leu Ala Val Ser Ala Leu Ser Lys Lys Ala Lys Ala Leu Leu
195 200 205
Cys Asp Val Pro Phe Leu Cys His Phe Arg Arg Ala Val Gln Leu Val
210 215 220
Asp Thr His Pro Tyr Ala Glu Ile Thr Asn Phe Leu Lys Thr His Arg
225 230 235 240
Asp Lys Glu Glu Ile Val Phe Arg Thr Leu Ser Tyr Phe Asp Gly Val
245 250 255
Asn Phe Ala Ala Arg Ala Lys Ile Pro Ala Leu Phe Ser Val Gly Leu
260 265 270
Met Asp Asn Ile Ser Pro Pro Ser Thr Val Phe Ala Ala Tyr Asn Tyr
275 280 285
Tyr Ala Gly Pro Lys Glu Ile Arg Ile Tyr Pro Tyr Asn Asn His Glu
290 295 300
Gly Gly Gly Ser Phe Gln Ala Val Glu Gln Val Lys Phe Leu Lys Lys
305 310 315 320
Leu Phe Glu Lys Gly Gly Pro Gly Ser Gly Gly Ala Gly Ser Pro Gly
325 330 335
Ser Ala Gly Gly Pro Gly Ser Pro Ser Ala Gln Ser Gln Leu Pro Asp
340 345 350
Lys His Ser Gly Leu His Glu Arg Ala Pro Gln Arg Tyr Gly Pro Glu
355 360 365
Pro Glu Pro Glu Pro Glu Pro Ile Pro Glu Pro Pro Lys Glu Ala Pro
370 375 380
Val Val Ile Glu Lys Pro Lys Pro Lys Pro Lys Pro Lys Pro Lys Pro
385 390 395 400
Pro Ala His Asp His Lys Asn Gln Lys Glu Thr His Gln Arg His Ala
405 410 415
Ala Gly Ser Gly Gly Gly Gly Ser Pro His His His His His His
420 425 430
<210> 179
<211> 353
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 179
Met Ala Phe Phe Asp Leu Pro Leu Glu Glu Leu Lys Lys Tyr Arg Pro
1 5 10 15
Glu Arg Tyr Glu Glu Lys Asp Phe Asp Glu Phe Trp Glu Glu Thr Leu
20 25 30
Ala Glu Ser Glu Lys Phe Pro Leu Asp Pro Val Phe Glu Arg Met Glu
35 40 45
Ser His Leu Lys Thr Val Glu Ala Tyr Asp Val Thr Phe Ser Gly Tyr
50 55 60
Arg Gly Gln Arg Ile Lys Gly Trp Leu Leu Val Pro Lys Leu Glu Glu
65 70 75 80
Glu Lys Leu Pro Cys Val Val Gln Tyr Ile Gly Tyr Asn Gly Gly Arg
85 90 95
Gly Phe Pro His Asp Trp Leu Phe Trp Pro Ser Met Gly Tyr Ile Cys
100 105 110
Phe Val Met Asp Thr Arg Gly Gln Gly Ser Gly Trp Leu Lys Gly Asp
115 120 125
Thr Pro Asp Tyr Pro Glu Gly Pro Val Asp Pro Gln Tyr Pro Gly Phe
130 135 140
Met Thr Arg Gly Ile Leu Asp Pro Arg Thr Tyr Tyr Tyr Arg Arg Val
145 150 155 160
Phe Thr Asp Ala Val Arg Ala Val Glu Ala Ala Ala Ser Phe Pro Gln
165 170 175
Val Asp Gln Glu Arg Ile Val Ile Ala Gly Gly Ser Gln Gly Gly Gly
180 185 190
Ile Ala Leu Ala Val Ser Ala Leu Ser Lys Lys Ala Lys Ala Leu Leu
195 200 205
Cys Asp Val Pro Phe Leu Cys His Phe Arg Arg Ala Val Gln Leu Val
210 215 220
Asp Thr His Pro Tyr Ala Glu Ile Thr Asn Phe Leu Lys Thr His Arg
225 230 235 240
Asp Lys Glu Glu Ile Val Phe Arg Thr Leu Ser Tyr Phe Asp Gly Val
245 250 255
Asn Phe Ala Ala Arg Ala Lys Ile Pro Ala Leu Phe Ser Val Gly Leu
260 265 270
Met Asp Asn Ile Ser Pro Pro Ser Thr Val Phe Ala Ala Tyr Asn Tyr
275 280 285
Tyr Ala Gly Pro Lys Glu Ile Arg Ile Tyr Pro Tyr Asn Asn His Glu
290 295 300
Gly Gly Gly Ser Phe Gln Ala Val Glu Gln Val Lys Phe Leu Lys Lys
305 310 315 320
Leu Phe Glu Lys Gly Gly Pro Gly Ser Gly Gly Ala Gly Ser Pro Gly
325 330 335
Ser Ala Gly Gly Pro Gly Ser Gly Lys Gly Lys Gly Lys Gly Lys Gly
340 345 350
Lys
<210> 180
<211> 359
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 180
Met Ala Phe Phe Asp Leu Pro Leu Glu Glu Leu Lys Lys Tyr Arg Pro
1 5 10 15
Glu Arg Tyr Glu Glu Lys Asp Phe Asp Glu Phe Trp Glu Glu Thr Leu
20 25 30
Ala Glu Ser Glu Lys Phe Pro Leu Asp Pro Val Phe Glu Arg Met Glu
35 40 45
Ser His Leu Lys Thr Val Glu Ala Tyr Asp Val Thr Phe Ser Gly Tyr
50 55 60
Arg Gly Gln Arg Ile Lys Gly Trp Leu Leu Val Pro Lys Leu Glu Glu
65 70 75 80
Glu Lys Leu Pro Cys Val Val Gln Tyr Ile Gly Tyr Asn Gly Gly Arg
85 90 95
Gly Phe Pro His Asp Trp Leu Phe Trp Pro Ser Met Gly Tyr Ile Cys
100 105 110
Phe Val Met Asp Thr Arg Gly Gln Gly Ser Gly Trp Leu Lys Gly Asp
115 120 125
Thr Pro Asp Tyr Pro Glu Gly Pro Val Asp Pro Gln Tyr Pro Gly Phe
130 135 140
Met Thr Arg Gly Ile Leu Asp Pro Arg Thr Tyr Tyr Tyr Arg Arg Val
145 150 155 160
Phe Thr Asp Ala Val Arg Ala Val Glu Ala Ala Ala Ser Phe Pro Gln
165 170 175
Val Asp Gln Glu Arg Ile Val Ile Ala Gly Gly Ser Gln Gly Gly Gly
180 185 190
Ile Ala Leu Ala Val Ser Ala Leu Ser Lys Lys Ala Lys Ala Leu Leu
195 200 205
Cys Asp Val Pro Phe Leu Cys His Phe Arg Arg Ala Val Gln Leu Val
210 215 220
Asp Thr His Pro Tyr Ala Glu Ile Thr Asn Phe Leu Lys Thr His Arg
225 230 235 240
Asp Lys Glu Glu Ile Val Phe Arg Thr Leu Ser Tyr Phe Asp Gly Val
245 250 255
Asn Phe Ala Ala Arg Ala Lys Ile Pro Ala Leu Phe Ser Val Gly Leu
260 265 270
Met Asp Asn Ile Ser Pro Pro Ser Thr Val Phe Ala Ala Tyr Asn Tyr
275 280 285
Tyr Ala Gly Pro Lys Glu Ile Arg Ile Tyr Pro Tyr Asn Asn His Glu
290 295 300
Gly Gly Gly Ser Phe Gln Ala Val Glu Gln Val Lys Phe Leu Lys Lys
305 310 315 320
Leu Phe Glu Lys Gly Gly Pro Gly Ser Gly Gly Ala Gly Ser Pro Gly
325 330 335
Ser Ala Gly Gly Pro Gly Ser Gly Lys Gly Lys Gly Lys Gly Lys Gly
340 345 350
Lys His His His His His His
355
<210> 181
<211> 375
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 181
Met Ala Phe Phe Asp Leu Pro Leu Glu Glu Leu Lys Lys Tyr Arg Pro
1 5 10 15
Glu Arg Tyr Glu Glu Lys Asp Phe Asp Glu Phe Trp Glu Glu Thr Leu
20 25 30
Ala Glu Ser Glu Lys Phe Pro Leu Asp Pro Val Phe Glu Arg Met Glu
35 40 45
Ser His Leu Lys Thr Val Glu Ala Tyr Asp Val Thr Phe Ser Gly Tyr
50 55 60
Arg Gly Gln Arg Ile Lys Gly Trp Leu Leu Val Pro Lys Leu Glu Glu
65 70 75 80
Glu Lys Leu Pro Cys Val Val Gln Tyr Ile Gly Tyr Asn Gly Gly Arg
85 90 95
Gly Phe Pro His Asp Trp Leu Phe Trp Pro Ser Met Gly Tyr Ile Cys
100 105 110
Phe Val Met Asp Thr Arg Gly Gln Gly Ser Gly Trp Leu Lys Gly Asp
115 120 125
Thr Pro Asp Tyr Pro Glu Gly Pro Val Asp Pro Gln Tyr Pro Gly Phe
130 135 140
Met Thr Arg Gly Ile Leu Asp Pro Arg Thr Tyr Tyr Tyr Arg Arg Val
145 150 155 160
Phe Thr Asp Ala Val Arg Ala Val Glu Ala Ala Ala Ser Phe Pro Gln
165 170 175
Val Asp Gln Glu Arg Ile Val Ile Ala Gly Gly Ser Gln Gly Gly Gly
180 185 190
Ile Ala Leu Ala Val Ser Ala Leu Ser Lys Lys Ala Lys Ala Leu Leu
195 200 205
Cys Asp Val Pro Phe Leu Cys His Phe Arg Arg Ala Val Gln Leu Val
210 215 220
Asp Thr His Pro Tyr Ala Glu Ile Thr Asn Phe Leu Lys Thr His Arg
225 230 235 240
Asp Lys Glu Glu Ile Val Phe Arg Thr Leu Ser Tyr Phe Asp Gly Val
245 250 255
Asn Phe Ala Ala Arg Ala Lys Ile Pro Ala Leu Phe Ser Val Gly Leu
260 265 270
Met Asp Asn Ile Thr Pro Pro Ser Thr Val Phe Ala Ala Tyr Asn Tyr
275 280 285
Tyr Ala Gly Pro Lys Glu Ile Arg Ile Tyr Pro Tyr Asn Asn His Glu
290 295 300
Gly Gly Gly Ser Phe Gln Ala Val Glu Gln Val Lys Phe Leu Lys Lys
305 310 315 320
Leu Phe Glu Lys Gly Gly Pro Gly Ser Gly Gly Ala Gly Ser Pro Gly
325 330 335
Ser Ala Gly Gly Pro Gly Ser Thr Lys Pro Pro Arg Thr Pro Thr Ala
340 345 350
Asn Thr Ser Arg Pro His His Asn Phe Gly Ser Gly Gly Gly Gly Ser
355 360 365
Pro His His His His His His
370 375
<210> 182
<211> 431
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 182
Met Ala Phe Phe Asp Leu Pro Leu Glu Glu Leu Lys Lys Tyr Arg Pro
1 5 10 15
Glu Arg Tyr Glu Glu Lys Asp Phe Asp Glu Phe Trp Glu Glu Thr Leu
20 25 30
Ala Glu Ser Glu Lys Phe Pro Leu Asp Pro Val Phe Glu Arg Met Glu
35 40 45
Ser His Leu Lys Thr Val Glu Ala Tyr Asp Val Thr Phe Ser Gly Tyr
50 55 60
Arg Gly Gln Arg Ile Lys Gly Trp Leu Leu Val Pro Lys Leu Glu Glu
65 70 75 80
Glu Lys Leu Pro Cys Val Val Gln Tyr Ile Gly Tyr Asn Gly Gly Arg
85 90 95
Gly Phe Pro His Asp Trp Leu Phe Trp Pro Ser Met Gly Tyr Ile Cys
100 105 110
Phe Val Met Asp Thr Arg Gly Gln Gly Ser Gly Trp Leu Lys Gly Asp
115 120 125
Thr Pro Asp Tyr Pro Glu Gly Pro Val Asp Pro Gln Tyr Pro Gly Phe
130 135 140
Met Thr Arg Gly Ile Leu Asp Pro Arg Thr Tyr Tyr Tyr Arg Arg Val
145 150 155 160
Phe Thr Asp Ala Val Arg Ala Val Glu Ala Ala Ala Ser Phe Pro Gln
165 170 175
Val Asp Gln Glu Arg Ile Val Ile Ala Gly Gly Ser Gln Gly Gly Gly
180 185 190
Ile Ala Leu Ala Val Ser Ala Leu Ser Lys Lys Ala Lys Ala Leu Leu
195 200 205
Cys Asp Val Pro Phe Leu Cys His Phe Arg Arg Ala Val Gln Leu Val
210 215 220
Asp Thr His Pro Tyr Ala Glu Ile Thr Asn Phe Leu Lys Thr His Arg
225 230 235 240
Asp Lys Glu Glu Ile Val Phe Arg Thr Leu Ser Tyr Phe Asp Gly Val
245 250 255
Asn Phe Ala Ala Arg Ala Lys Ile Pro Ala Leu Phe Ser Val Gly Leu
260 265 270
Met Asp Asn Ile Thr Pro Pro Ser Thr Val Phe Ala Ala Tyr Asn Tyr
275 280 285
Tyr Ala Gly Pro Lys Glu Ile Arg Ile Tyr Pro Tyr Asn Asn His Glu
290 295 300
Gly Gly Gly Ser Phe Gln Ala Val Glu Gln Val Lys Phe Leu Lys Lys
305 310 315 320
Leu Phe Glu Lys Gly Gly Pro Gly Ser Gly Gly Ala Gly Ser Pro Gly
325 330 335
Ser Ala Gly Gly Pro Gly Ser Pro Ser Ala Gln Ser Gln Leu Pro Asp
340 345 350
Lys His Ser Gly Leu His Glu Arg Ala Pro Gln Arg Tyr Gly Pro Glu
355 360 365
Pro Glu Pro Glu Pro Glu Pro Ile Pro Glu Pro Pro Lys Glu Ala Pro
370 375 380
Val Val Ile Glu Lys Pro Lys Pro Lys Pro Lys Pro Lys Pro Lys Pro
385 390 395 400
Pro Ala His Asp His Lys Asn Gln Lys Glu Thr His Gln Arg His Ala
405 410 415
Ala Gly Ser Gly Gly Gly Gly Ser Pro His His His His His His
420 425 430
<210> 183
<211> 359
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 183
Met Ala Phe Phe Asp Leu Pro Leu Glu Glu Leu Lys Lys Tyr Arg Pro
1 5 10 15
Glu Arg Tyr Glu Glu Lys Asp Phe Asp Glu Phe Trp Glu Glu Thr Leu
20 25 30
Ala Glu Ser Glu Lys Phe Pro Leu Asp Pro Val Phe Glu Arg Met Glu
35 40 45
Ser His Leu Lys Thr Val Glu Ala Tyr Asp Val Thr Phe Ser Gly Tyr
50 55 60
Arg Gly Gln Arg Ile Lys Gly Trp Leu Leu Val Pro Lys Leu Glu Glu
65 70 75 80
Glu Lys Leu Pro Cys Val Val Gln Tyr Ile Gly Tyr Asn Gly Gly Arg
85 90 95
Gly Phe Pro His Asp Trp Leu Phe Trp Pro Ser Met Gly Tyr Ile Cys
100 105 110
Phe Val Met Asp Thr Arg Gly Gln Gly Ser Gly Trp Leu Lys Gly Asp
115 120 125
Thr Pro Asp Tyr Pro Glu Gly Pro Val Asp Pro Gln Tyr Pro Gly Phe
130 135 140
Met Thr Arg Gly Ile Leu Asp Pro Arg Thr Tyr Tyr Tyr Arg Arg Val
145 150 155 160
Phe Thr Asp Ala Val Arg Ala Val Glu Ala Ala Ala Ser Phe Pro Gln
165 170 175
Val Asp Gln Glu Arg Ile Val Ile Ala Gly Gly Ser Gln Gly Gly Gly
180 185 190
Ile Ala Leu Ala Val Ser Ala Leu Ser Lys Lys Ala Lys Ala Leu Leu
195 200 205
Cys Asp Val Pro Phe Leu Cys His Phe Arg Arg Ala Val Gln Leu Val
210 215 220
Asp Thr His Pro Tyr Ala Glu Ile Thr Asn Phe Leu Lys Thr His Arg
225 230 235 240
Asp Lys Glu Glu Ile Val Phe Arg Thr Leu Ser Tyr Phe Asp Gly Val
245 250 255
Asn Phe Ala Ala Arg Ala Lys Ile Pro Ala Leu Phe Ser Val Gly Leu
260 265 270
Met Asp Asn Ile Thr Pro Pro Ser Thr Val Phe Ala Ala Tyr Asn Tyr
275 280 285
Tyr Ala Gly Pro Lys Glu Ile Arg Ile Tyr Pro Tyr Asn Asn His Glu
290 295 300
Gly Gly Gly Ser Phe Gln Ala Val Glu Gln Val Lys Phe Leu Lys Lys
305 310 315 320
Leu Phe Glu Lys Gly Gly Pro Gly Ser Gly Gly Ala Gly Ser Pro Gly
325 330 335
Ser Ala Gly Gly Pro Gly Ser Gly Lys Gly Lys Gly Lys Gly Lys Gly
340 345 350
Lys His His His His His His
355
<210> 184
<211> 386
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 184
Met Ala Phe Phe Asp Leu Pro Leu Glu Glu Leu Lys Lys Tyr Arg Pro
1 5 10 15
Glu Arg Tyr Glu Glu Lys Asp Phe Asp Glu Phe Trp Glu Glu Thr Leu
20 25 30
Ala Glu Ser Glu Lys Phe Pro Leu Asp Pro Val Phe Glu Arg Met Glu
35 40 45
Ser His Leu Lys Thr Val Glu Ala Tyr Asp Val Thr Phe Ser Gly Tyr
50 55 60
Arg Gly Gln Arg Ile Lys Gly Trp Leu Leu Val Pro Lys Leu Glu Glu
65 70 75 80
Glu Lys Leu Pro Cys Val Val Gln Tyr Ile Gly Tyr Asn Gly Gly Arg
85 90 95
Gly Phe Pro His Asp Trp Leu Phe Trp Pro Ser Met Gly Tyr Ile Cys
100 105 110
Phe Val Met Asp Thr Arg Gly Gln Gly Ser Gly Trp Leu Lys Gly Asp
115 120 125
Thr Pro Asp Tyr Pro Glu Gly Pro Val Asp Pro Gln Tyr Pro Gly Phe
130 135 140
Met Thr Arg Gly Ile Leu Asp Pro Arg Thr Tyr Tyr Tyr Arg Arg Val
145 150 155 160
Phe Thr Asp Ala Val Arg Ala Val Glu Ala Ala Ala Ser Phe Pro Gln
165 170 175
Val Asp Gln Glu Arg Ile Val Ile Ala Gly Gly Ser Gln Gly Gly Gly
180 185 190
Ile Ala Leu Ala Val Ser Ala Leu Ser Lys Lys Ala Lys Ala Leu Leu
195 200 205
Cys Asp Val Pro Phe Leu Cys His Phe Arg Arg Ala Val Gln Leu Val
210 215 220
Asp Thr His Pro Tyr Ala Glu Ile Thr Asn Phe Leu Lys Thr His Arg
225 230 235 240
Asp Lys Glu Glu Ile Val Phe Arg Thr Leu Ser Tyr Phe Asp Gly Val
245 250 255
Asn Phe Ala Ala Arg Ala Lys Ile Pro Ala Leu Phe Ser Val Gly Leu
260 265 270
Met Asp Asn Ile Ser Pro Pro Ser Thr Val Phe Ala Ala Tyr Asn Tyr
275 280 285
Tyr Ala Gly Pro Lys Glu Ile Arg Ile Tyr Pro Tyr Asn Asn His Glu
290 295 300
Gly Gly Gly Ser Phe Gln Ala Val Glu Gln Val Lys Phe Leu Lys Lys
305 310 315 320
Leu Phe Glu Lys Gly Glu Pro Glu Pro Glu Gly Pro Gly Ser Gly Gly
325 330 335
Ala Gly Ser Pro Gly Ser Ala Gly Gly Pro Gly Ser Glu Pro Glu Pro
340 345 350
Glu Trp Lys Thr Lys Lys Ile Leu Leu Ser Arg Thr Arg Arg Ile Met
355 360 365
Arg Gln Val Val Arg Ser Val Met His Lys Ile Trp His His His His
370 375 380
His His
385
<210> 185
<211> 387
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 185
Met Ala Phe Phe Asp Leu Pro Leu Glu Glu Leu Lys Lys Tyr Arg Pro
1 5 10 15
Glu Arg Tyr Glu Glu Lys Asp Phe Asp Glu Phe Trp Glu Glu Thr Leu
20 25 30
Ala Glu Ser Glu Lys Phe Pro Leu Asp Pro Val Phe Glu Arg Met Glu
35 40 45
Ser His Leu Lys Thr Val Glu Ala Tyr Asp Val Thr Phe Ser Gly Tyr
50 55 60
Arg Gly Gln Arg Ile Lys Gly Trp Leu Leu Val Pro Lys Leu Glu Glu
65 70 75 80
Glu Lys Leu Pro Cys Val Val Gln Tyr Ile Gly Tyr Asn Gly Gly Arg
85 90 95
Gly Phe Pro His Asp Trp Leu Phe Trp Pro Ser Met Gly Tyr Ile Cys
100 105 110
Phe Val Met Asp Thr Arg Gly Gln Gly Ser Gly Trp Leu Lys Gly Asp
115 120 125
Thr Pro Asp Tyr Pro Glu Gly Pro Val Asp Pro Gln Tyr Pro Gly Phe
130 135 140
Met Thr Arg Gly Ile Leu Asp Pro Arg Thr Tyr Tyr Tyr Arg Arg Val
145 150 155 160
Phe Thr Asp Ala Val Arg Ala Val Glu Ala Ala Ala Ser Phe Pro Gln
165 170 175
Val Asp Gln Glu Arg Ile Val Ile Ala Gly Gly Ser Gln Gly Gly Gly
180 185 190
Ile Ala Leu Ala Val Ser Ala Leu Ser Lys Lys Ala Lys Ala Leu Leu
195 200 205
Cys Asp Val Pro Phe Leu Cys His Phe Arg Arg Ala Val Gln Leu Val
210 215 220
Asp Thr His Pro Tyr Ala Glu Ile Thr Asn Phe Leu Lys Thr His Arg
225 230 235 240
Asp Lys Glu Glu Ile Val Phe Arg Thr Leu Ser Tyr Phe Asp Gly Val
245 250 255
Asn Phe Ala Ala Arg Ala Lys Ile Pro Ala Leu Phe Ser Val Gly Leu
260 265 270
Met Asp Asn Ile Ser Pro Pro Ser Thr Val Phe Ala Ala Tyr Asn Tyr
275 280 285
Tyr Ala Gly Pro Lys Glu Ile Arg Ile Tyr Pro Tyr Asn Asn His Glu
290 295 300
Gly Gly Gly Ser Phe Gln Ala Val Glu Gln Val Lys Phe Leu Lys Lys
305 310 315 320
Leu Phe Glu Lys Gly Glu Pro Glu Pro Glu Pro Glu Pro Glu Pro Glu
325 330 335
Gly Pro Gly Ser Gly Gly Ala Gly Ser Pro Gly Ser Ala Gly Gly Pro
340 345 350
Gly Ser Trp Lys Thr Lys Lys Ile Leu Leu Ser Arg Thr Arg Arg Ile
355 360 365
Met Arg Gln Val Val Arg Ser Val Met His Lys Ile Trp His His His
370 375 380
His His His
385
<210> 186
<211> 386
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 186
Met Ala Phe Phe Asp Leu Pro Leu Glu Glu Leu Lys Lys Tyr Arg Pro
1 5 10 15
Glu Arg Tyr Glu Glu Lys Asp Phe Asp Glu Phe Trp Glu Glu Thr Leu
20 25 30
Ala Glu Ser Glu Lys Phe Pro Leu Asp Pro Val Phe Glu Arg Met Glu
35 40 45
Ser His Leu Lys Thr Val Glu Ala Tyr Asp Val Thr Phe Ser Gly Tyr
50 55 60
Arg Gly Gln Arg Ile Lys Gly Trp Leu Leu Val Pro Lys Leu Glu Glu
65 70 75 80
Glu Lys Leu Pro Cys Val Val Gln Tyr Ile Gly Tyr Asn Gly Gly Arg
85 90 95
Gly Phe Pro His Asp Trp Leu Phe Trp Pro Ser Met Gly Tyr Ile Cys
100 105 110
Phe Val Met Asp Thr Arg Gly Gln Gly Ser Gly Trp Leu Lys Gly Asp
115 120 125
Thr Pro Asp Tyr Pro Glu Gly Pro Val Asp Pro Gln Tyr Pro Gly Phe
130 135 140
Met Thr Arg Gly Ile Leu Asp Pro Arg Thr Tyr Tyr Tyr Arg Arg Val
145 150 155 160
Phe Thr Asp Ala Val Arg Ala Val Glu Ala Ala Ala Ser Phe Pro Gln
165 170 175
Val Asp Gln Glu Arg Ile Val Ile Ala Gly Gly Ser Gln Gly Gly Gly
180 185 190
Ile Ala Leu Ala Val Ser Ala Leu Ser Lys Lys Ala Lys Ala Leu Leu
195 200 205
Cys Asp Val Pro Phe Leu Cys His Phe Arg Arg Ala Val Gln Leu Val
210 215 220
Asp Thr His Pro Tyr Ala Glu Ile Thr Asn Phe Leu Lys Thr His Arg
225 230 235 240
Asp Lys Glu Glu Ile Val Phe Arg Thr Leu Ser Tyr Phe Asp Gly Val
245 250 255
Asn Phe Ala Ala Arg Ala Lys Ile Pro Ala Leu Phe Ser Val Gly Leu
260 265 270
Met Asp Asn Ile Ser Pro Pro Ser Thr Val Phe Ala Ala Tyr Asn Tyr
275 280 285
Tyr Ala Gly Pro Lys Glu Ile Arg Ile Tyr Pro Tyr Asn Asn His Glu
290 295 300
Gly Gly Gly Ser Phe Gln Ala Val Glu Gln Val Lys Phe Leu Lys Lys
305 310 315 320
Leu Phe Glu Lys Gly Glu Pro Glu Pro Glu Gly Pro Gly Ser Gly Gly
325 330 335
Ala Gly Ser Pro Gly Ser Ala Gly Gly Pro Gly Ser Glu Pro Glu Pro
340 345 350
Glu Pro Leu Trp Arg Arg Ile Thr Lys Arg Lys Leu Val Arg Pro Val
355 360 365
Ala Thr Leu Met Trp Tyr Trp Phe Thr Ser Lys Arg His His His His
370 375 380
His His
385
<210> 187
<211> 387
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 187
Met Ala Phe Phe Asp Leu Pro Leu Glu Glu Leu Lys Lys Tyr Arg Pro
1 5 10 15
Glu Arg Tyr Glu Glu Lys Asp Phe Asp Glu Phe Trp Glu Glu Thr Leu
20 25 30
Ala Glu Ser Glu Lys Phe Pro Leu Asp Pro Val Phe Glu Arg Met Glu
35 40 45
Ser His Leu Lys Thr Val Glu Ala Tyr Asp Val Thr Phe Ser Gly Tyr
50 55 60
Arg Gly Gln Arg Ile Lys Gly Trp Leu Leu Val Pro Lys Leu Glu Glu
65 70 75 80
Glu Lys Leu Pro Cys Val Val Gln Tyr Ile Gly Tyr Asn Gly Gly Arg
85 90 95
Gly Phe Pro His Asp Trp Leu Phe Trp Pro Ser Met Gly Tyr Ile Cys
100 105 110
Phe Val Met Asp Thr Arg Gly Gln Gly Ser Gly Trp Leu Lys Gly Asp
115 120 125
Thr Pro Asp Tyr Pro Glu Gly Pro Val Asp Pro Gln Tyr Pro Gly Phe
130 135 140
Met Thr Arg Gly Ile Leu Asp Pro Arg Thr Tyr Tyr Tyr Arg Arg Val
145 150 155 160
Phe Thr Asp Ala Val Arg Ala Val Glu Ala Ala Ala Ser Phe Pro Gln
165 170 175
Val Asp Gln Glu Arg Ile Val Ile Ala Gly Gly Ser Gln Gly Gly Gly
180 185 190
Ile Ala Leu Ala Val Ser Ala Leu Ser Lys Lys Ala Lys Ala Leu Leu
195 200 205
Cys Asp Val Pro Phe Leu Cys His Phe Arg Arg Ala Val Gln Leu Val
210 215 220
Asp Thr His Pro Tyr Ala Glu Ile Thr Asn Phe Leu Lys Thr His Arg
225 230 235 240
Asp Lys Glu Glu Ile Val Phe Arg Thr Leu Ser Tyr Phe Asp Gly Val
245 250 255
Asn Phe Ala Ala Arg Ala Lys Ile Pro Ala Leu Phe Ser Val Gly Leu
260 265 270
Met Asp Asn Ile Ser Pro Pro Ser Thr Val Phe Ala Ala Tyr Asn Tyr
275 280 285
Tyr Ala Gly Pro Lys Glu Ile Arg Ile Tyr Pro Tyr Asn Asn His Glu
290 295 300
Gly Gly Gly Ser Phe Gln Ala Val Glu Gln Val Lys Phe Leu Lys Lys
305 310 315 320
Leu Phe Glu Lys Gly Glu Pro Glu Pro Glu Pro Glu Pro Glu Pro Glu
325 330 335
Gly Pro Gly Ser Gly Gly Ala Gly Ser Pro Gly Ser Ala Gly Gly Pro
340 345 350
Gly Ser Pro Leu Trp Arg Arg Ile Thr Lys Arg Lys Leu Val Arg Pro
355 360 365
Val Ala Thr Leu Met Trp Tyr Trp Phe Thr Ser Lys Arg His His His
370 375 380
His His His
385
<210> 188
<211> 382
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 188
Met Ala Phe Phe Asp Leu Pro Leu Glu Glu Leu Lys Lys Tyr Arg Pro
1 5 10 15
Glu Arg Tyr Glu Glu Lys Asp Phe Asp Glu Phe Trp Glu Glu Thr Leu
20 25 30
Ala Glu Ser Glu Lys Phe Pro Leu Asp Pro Val Phe Glu Arg Met Glu
35 40 45
Ser His Leu Lys Thr Val Glu Ala Tyr Asp Val Thr Phe Ser Gly Tyr
50 55 60
Arg Gly Gln Arg Ile Lys Gly Trp Leu Leu Val Pro Lys Leu Glu Glu
65 70 75 80
Glu Lys Leu Pro Cys Val Val Gln Tyr Ile Gly Tyr Asn Gly Gly Arg
85 90 95
Gly Phe Pro His Asp Trp Leu Phe Trp Pro Ser Met Gly Tyr Ile Cys
100 105 110
Phe Val Met Asp Thr Arg Gly Gln Gly Ser Gly Trp Leu Lys Gly Asp
115 120 125
Thr Pro Asp Tyr Pro Glu Gly Pro Val Asp Pro Gln Tyr Pro Gly Phe
130 135 140
Met Thr Arg Gly Ile Leu Asp Pro Arg Thr Tyr Tyr Tyr Arg Arg Val
145 150 155 160
Phe Thr Asp Ala Val Arg Ala Val Glu Ala Ala Ala Ser Phe Pro Gln
165 170 175
Val Asp Gln Glu Arg Ile Val Ile Ala Gly Gly Ser Gln Gly Gly Gly
180 185 190
Ile Ala Leu Ala Val Ser Ala Leu Ser Lys Lys Ala Lys Ala Leu Leu
195 200 205
Cys Asp Val Pro Phe Leu Cys His Phe Arg Arg Ala Val Gln Leu Val
210 215 220
Asp Thr His Pro Tyr Ala Glu Ile Thr Asn Phe Leu Lys Thr His Arg
225 230 235 240
Asp Lys Glu Glu Ile Val Phe Arg Thr Leu Ser Tyr Phe Asp Gly Val
245 250 255
Asn Phe Ala Ala Arg Ala Lys Ile Pro Ala Leu Phe Ser Val Gly Leu
260 265 270
Met Asp Asn Ile Ser Pro Pro Ser Thr Val Phe Ala Ala Tyr Asn Tyr
275 280 285
Tyr Ala Gly Pro Lys Glu Ile Arg Ile Tyr Pro Tyr Asn Asn His Glu
290 295 300
Gly Gly Gly Ser Phe Gln Ala Val Glu Gln Val Lys Phe Leu Lys Lys
305 310 315 320
Leu Phe Glu Lys Gly Glu Pro Glu Gly Pro Gly Ser Gly Gly Ala Gly
325 330 335
Ser Pro Gly Ser Ala Gly Gly Pro Gly Ser Glu Pro Glu Arg Met Leu
340 345 350
Ser Arg Ile Leu Arg Met Phe Val Arg Ile Leu Lys Arg Glu Arg Leu
355 360 365
Ser Gln Val Arg Gly Leu Phe Val His His His His His His
370 375 380
<210> 189
<211> 383
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 189
Met Ala Phe Phe Asp Leu Pro Leu Glu Glu Leu Lys Lys Tyr Arg Pro
1 5 10 15
Glu Arg Tyr Glu Glu Lys Asp Phe Asp Glu Phe Trp Glu Glu Thr Leu
20 25 30
Ala Glu Ser Glu Lys Phe Pro Leu Asp Pro Val Phe Glu Arg Met Glu
35 40 45
Ser His Leu Lys Thr Val Glu Ala Tyr Asp Val Thr Phe Ser Gly Tyr
50 55 60
Arg Gly Gln Arg Ile Lys Gly Trp Leu Leu Val Pro Lys Leu Glu Glu
65 70 75 80
Glu Lys Leu Pro Cys Val Val Gln Tyr Ile Gly Tyr Asn Gly Gly Arg
85 90 95
Gly Phe Pro His Asp Trp Leu Phe Trp Pro Ser Met Gly Tyr Ile Cys
100 105 110
Phe Val Met Asp Thr Arg Gly Gln Gly Ser Gly Trp Leu Lys Gly Asp
115 120 125
Thr Pro Asp Tyr Pro Glu Gly Pro Val Asp Pro Gln Tyr Pro Gly Phe
130 135 140
Met Thr Arg Gly Ile Leu Asp Pro Arg Thr Tyr Tyr Tyr Arg Arg Val
145 150 155 160
Phe Thr Asp Ala Val Arg Ala Val Glu Ala Ala Ala Ser Phe Pro Gln
165 170 175
Val Asp Gln Glu Arg Ile Val Ile Ala Gly Gly Ser Gln Gly Gly Gly
180 185 190
Ile Ala Leu Ala Val Ser Ala Leu Ser Lys Lys Ala Lys Ala Leu Leu
195 200 205
Cys Asp Val Pro Phe Leu Cys His Phe Arg Arg Ala Val Gln Leu Val
210 215 220
Asp Thr His Pro Tyr Ala Glu Ile Thr Asn Phe Leu Lys Thr His Arg
225 230 235 240
Asp Lys Glu Glu Ile Val Phe Arg Thr Leu Ser Tyr Phe Asp Gly Val
245 250 255
Asn Phe Ala Ala Arg Ala Lys Ile Pro Ala Leu Phe Ser Val Gly Leu
260 265 270
Met Asp Asn Ile Ser Pro Pro Ser Thr Val Phe Ala Ala Tyr Asn Tyr
275 280 285
Tyr Ala Gly Pro Lys Glu Ile Arg Ile Tyr Pro Tyr Asn Asn His Glu
290 295 300
Gly Gly Gly Ser Phe Gln Ala Val Glu Gln Val Lys Phe Leu Lys Lys
305 310 315 320
Leu Phe Glu Lys Gly Glu Pro Glu Pro Glu Pro Glu Gly Pro Gly Ser
325 330 335
Gly Gly Ala Gly Ser Pro Gly Ser Ala Gly Gly Pro Gly Ser Arg Met
340 345 350
Leu Ser Arg Ile Leu Arg Met Phe Val Arg Ile Leu Lys Arg Glu Arg
355 360 365
Leu Ser Gln Val Arg Gly Leu Phe Val His His His His His His
370 375 380
<210> 190
<211> 390
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 190
Met Ala Phe Phe Asp Leu Pro Leu Glu Glu Leu Lys Lys Tyr Arg Pro
1 5 10 15
Glu Arg Tyr Glu Glu Lys Asp Phe Asp Glu Phe Trp Glu Glu Thr Leu
20 25 30
Ala Glu Ser Glu Lys Phe Pro Leu Asp Pro Val Phe Glu Arg Met Glu
35 40 45
Ser His Leu Lys Thr Val Glu Ala Tyr Asp Val Thr Phe Ser Gly Tyr
50 55 60
Arg Gly Gln Arg Ile Lys Gly Trp Leu Leu Val Pro Lys Leu Glu Glu
65 70 75 80
Glu Lys Leu Pro Cys Val Val Gln Tyr Ile Gly Tyr Asn Gly Gly Arg
85 90 95
Gly Phe Pro His Asp Trp Leu Phe Trp Pro Ser Met Gly Tyr Ile Cys
100 105 110
Phe Val Met Asp Thr Arg Gly Gln Gly Ser Gly Trp Leu Lys Gly Asp
115 120 125
Thr Pro Asp Tyr Pro Glu Gly Pro Val Asp Pro Gln Tyr Pro Gly Phe
130 135 140
Met Thr Arg Gly Ile Leu Asp Pro Arg Thr Tyr Tyr Tyr Arg Arg Val
145 150 155 160
Phe Thr Asp Ala Val Arg Ala Val Glu Ala Ala Ala Ser Phe Pro Gln
165 170 175
Val Asp Gln Glu Arg Ile Val Ile Ala Gly Gly Ser Gln Gly Gly Gly
180 185 190
Ile Ala Leu Ala Val Ser Ala Leu Ser Lys Lys Ala Lys Ala Leu Leu
195 200 205
Cys Asp Val Pro Phe Leu Cys His Phe Arg Arg Ala Val Gln Leu Val
210 215 220
Asp Thr His Pro Tyr Ala Glu Ile Thr Asn Phe Leu Lys Thr His Arg
225 230 235 240
Asp Lys Glu Glu Ile Val Phe Arg Thr Leu Ser Tyr Phe Asp Gly Val
245 250 255
Asn Phe Ala Ala Arg Ala Lys Ile Pro Ala Leu Phe Ser Val Gly Leu
260 265 270
Met Asp Asn Ile Ser Pro Pro Ser Thr Val Phe Ala Ala Tyr Asn Tyr
275 280 285
Tyr Ala Gly Pro Lys Glu Ile Arg Ile Tyr Pro Tyr Asn Asn His Glu
290 295 300
Gly Gly Gly Ser Phe Gln Ala Val Glu Gln Val Lys Phe Leu Lys Lys
305 310 315 320
Leu Phe Glu Lys Gly Glu Pro Glu Pro Glu Pro Glu Gly Pro Gly Ser
325 330 335
Gly Gly Ala Gly Ser Pro Gly Ser Ala Gly Gly Pro Gly Ser Glu Pro
340 345 350
Glu Pro Glu Pro Glu Leu Arg Phe Leu Ala Arg Arg Phe Leu Lys Leu
355 360 365
Arg Arg Ala Arg Lys Trp Trp Asn Ala Trp Lys Val Trp Val Thr Arg
370 375 380
His His His His His His
385 390
<210> 191
<211> 391
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 191
Met Ala Phe Phe Asp Leu Pro Leu Glu Glu Leu Lys Lys Tyr Arg Pro
1 5 10 15
Glu Arg Tyr Glu Glu Lys Asp Phe Asp Glu Phe Trp Glu Glu Thr Leu
20 25 30
Ala Glu Ser Glu Lys Phe Pro Leu Asp Pro Val Phe Glu Arg Met Glu
35 40 45
Ser His Leu Lys Thr Val Glu Ala Tyr Asp Val Thr Phe Ser Gly Tyr
50 55 60
Arg Gly Gln Arg Ile Lys Gly Trp Leu Leu Val Pro Lys Leu Glu Glu
65 70 75 80
Glu Lys Leu Pro Cys Val Val Gln Tyr Ile Gly Tyr Asn Gly Gly Arg
85 90 95
Gly Phe Pro His Asp Trp Leu Phe Trp Pro Ser Met Gly Tyr Ile Cys
100 105 110
Phe Val Met Asp Thr Arg Gly Gln Gly Ser Gly Trp Leu Lys Gly Asp
115 120 125
Thr Pro Asp Tyr Pro Glu Gly Pro Val Asp Pro Gln Tyr Pro Gly Phe
130 135 140
Met Thr Arg Gly Ile Leu Asp Pro Arg Thr Tyr Tyr Tyr Arg Arg Val
145 150 155 160
Phe Thr Asp Ala Val Arg Ala Val Glu Ala Ala Ala Ser Phe Pro Gln
165 170 175
Val Asp Gln Glu Arg Ile Val Ile Ala Gly Gly Ser Gln Gly Gly Gly
180 185 190
Ile Ala Leu Ala Val Ser Ala Leu Ser Lys Lys Ala Lys Ala Leu Leu
195 200 205
Cys Asp Val Pro Phe Leu Cys His Phe Arg Arg Ala Val Gln Leu Val
210 215 220
Asp Thr His Pro Tyr Ala Glu Ile Thr Asn Phe Leu Lys Thr His Arg
225 230 235 240
Asp Lys Glu Glu Ile Val Phe Arg Thr Leu Ser Tyr Phe Asp Gly Val
245 250 255
Asn Phe Ala Ala Arg Ala Lys Ile Pro Ala Leu Phe Ser Val Gly Leu
260 265 270
Met Asp Asn Ile Ser Pro Pro Ser Thr Val Phe Ala Ala Tyr Asn Tyr
275 280 285
Tyr Ala Gly Pro Lys Glu Ile Arg Ile Tyr Pro Tyr Asn Asn His Glu
290 295 300
Gly Gly Gly Ser Phe Gln Ala Val Glu Gln Val Lys Phe Leu Lys Lys
305 310 315 320
Leu Phe Glu Lys Gly Glu Pro Glu Pro Glu Pro Glu Pro Glu Pro Glu
325 330 335
Pro Glu Pro Glu Gly Pro Gly Ser Gly Gly Ala Gly Ser Pro Gly Ser
340 345 350
Ala Gly Gly Pro Gly Ser Leu Arg Phe Leu Ala Arg Arg Phe Leu Lys
355 360 365
Leu Arg Arg Ala Arg Lys Trp Trp Asn Ala Trp Lys Val Trp Val Thr
370 375 380
Arg His His His His His His
385 390
<210> 192
<211> 426
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 192
Met Gln Leu Phe Asp Leu Ser Leu Glu Glu Leu Lys Lys Tyr Lys Pro
1 5 10 15
Lys Lys Thr Ala Arg Pro Asp Phe Ser Asp Phe Trp Lys Lys Ser Leu
20 25 30
Glu Glu Leu Arg Gln Val Glu Ala Glu Pro Thr Leu Glu Ser Tyr Asp
35 40 45
Tyr Pro Val Lys Gly Val Lys Val Tyr Arg Leu Thr Tyr Gln Ser Phe
50 55 60
Gly His Ser Lys Ile Glu Gly Phe Tyr Ala Val Pro Asp Gln Thr Gly
65 70 75 80
Pro His Pro Ala Leu Val Arg Phe His Gly Tyr Asn Ala Ser Tyr Asp
85 90 95
Gly Gly Ile His Asp Ile Val Asn Trp Ala Leu His Gly Tyr Ala Thr
100 105 110
Phe Gly Met Leu Val Arg Gly Gln Gly Gly Ser Glu Asp Thr Ser Val
115 120 125
Thr Pro Gly Gly His Ala Leu Gly Trp Met Thr Lys Gly Ile Leu Ser
130 135 140
Lys Asp Thr Tyr Tyr Tyr Arg Gly Val Tyr Leu Asp Ala Val Arg Ala
145 150 155 160
Leu Glu Val Ile Gln Ser Phe Pro Glu Val Asp Glu His Arg Ile Gly
165 170 175
Val Ile Gly Gly Ser Gln Gly Gly Ala Leu Ala Ile Ala Ala Ala Ala
180 185 190
Leu Ser Asp Ile Pro Lys Val Val Val Ala Asp Tyr Pro Tyr Leu Ser
195 200 205
Asn Phe Glu Arg Ala Val Asp Val Ala Leu Glu Gln Pro Tyr Leu Glu
210 215 220
Ile Asn Ser Tyr Phe Arg Arg Asn Ser Asp Pro Lys Val Glu Glu Lys
225 230 235 240
Ala Phe Glu Thr Leu Ser Tyr Phe Asp Leu Ile Asn Leu Ala Gly Trp
245 250 255
Val Lys Gln Pro Thr Leu Met Ala Ile Gly Leu Ile Asp Lys Ile Thr
260 265 270
Pro Pro Ser Thr Val Phe Ala Ala Tyr Asn His Leu Glu Thr Asp Lys
275 280 285
Asp Leu Lys Val Tyr Arg Tyr Phe Gly His Glu Phe Ile Pro Ala Phe
290 295 300
Gln Thr Glu Lys Leu Ser Phe Leu Gln Lys His Leu Leu Leu Ser Thr
305 310 315 320
Gly Pro Gly Ser Gly Gly Ala Gly Ser Pro Gly Ser Ala Gly Gly Pro
325 330 335
Gly Ser Pro Ser Ala Gln Ser Gln Leu Pro Asp Lys His Ser Gly Leu
340 345 350
His Glu Arg Ala Pro Gln Arg Tyr Gly Pro Glu Pro Glu Pro Glu Pro
355 360 365
Glu Pro Ile Pro Glu Pro Pro Lys Glu Ala Pro Val Val Ile Glu Lys
370 375 380
Pro Lys Pro Lys Pro Lys Pro Lys Pro Lys Pro Pro Ala His Asp His
385 390 395 400
Lys Asn Gln Lys Glu Thr His Gln Arg His Ala Ala Gly Ser Gly Gly
405 410 415
Gly Gly Ser Pro His His His His His His
420 425
<210> 193
<211> 372
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 193
Met Gln Leu Phe Asp Leu Ser Leu Glu Glu Leu Lys Lys Tyr Lys Pro
1 5 10 15
Lys Lys Thr Ala Arg Pro Asp Phe Ser Asp Phe Trp Lys Lys Ser Leu
20 25 30
Glu Glu Leu Arg Gln Val Glu Ala Glu Pro Thr Leu Glu Ser Tyr Asp
35 40 45
Tyr Pro Val Lys Gly Val Lys Val Tyr Arg Leu Thr Tyr Gln Ser Phe
50 55 60
Gly His Ser Lys Ile Glu Gly Phe Tyr Ala Val Pro Asp Gln Thr Gly
65 70 75 80
Pro His Pro Ala Leu Val Arg Phe His Gly Tyr Asn Ala Ser Tyr Asp
85 90 95
Gly Gly Ile His Asp Ile Val Asn Trp Ala Leu His Gly Tyr Ala Thr
100 105 110
Phe Gly Met Leu Val Arg Gly Gln Gly Gly Ser Glu Asp Thr Ser Val
115 120 125
Thr Pro Gly Gly His Ala Leu Gly Trp Met Thr Lys Gly Ile Leu Ser
130 135 140
Lys Asp Thr Tyr Tyr Tyr Arg Gly Val Tyr Leu Asp Ala Val Arg Ala
145 150 155 160
Leu Glu Val Ile Gln Ser Phe Pro Glu Val Asp Glu His Arg Ile Gly
165 170 175
Val Ile Gly Gly Ser Gln Gly Gly Ala Leu Ala Ile Ala Ala Ala Ala
180 185 190
Leu Ser Asp Ile Pro Lys Val Val Val Ala Asp Tyr Pro Tyr Leu Ser
195 200 205
Asn Phe Glu Arg Ala Val Asp Val Ala Leu Glu Gln Pro Tyr Leu Glu
210 215 220
Ile Asn Ser Tyr Phe Arg Arg Asn Ser Asp Pro Lys Val Glu Glu Lys
225 230 235 240
Ala Phe Glu Thr Leu Ser Tyr Phe Asp Leu Ile Asn Leu Ala Gly Trp
245 250 255
Val Lys Gln Pro Thr Leu Met Ala Ile Gly Leu Ile Asp Lys Ile Thr
260 265 270
Pro Pro Ser Thr Val Phe Ala Ala Tyr Asn His Leu Glu Thr Asp Lys
275 280 285
Asp Leu Lys Val Tyr Arg Tyr Phe Gly His Glu Phe Ile Pro Ala Phe
290 295 300
Gln Thr Glu Lys Leu Ser Phe Leu Gln Lys His Leu Leu Leu Ser Thr
305 310 315 320
Gly Pro Gly Ser Gly Gly Ala Gly Ser Pro Gly Ser Ala Gly Gly Pro
325 330 335
Gly Ser Asp Pro Thr Lys Pro Pro Arg Thr Pro Thr Ala Asn Thr Ser
340 345 350
Arg Pro His His Asn Phe Gly Ser Gly Gly Gly Gly Ser Pro His His
355 360 365
His His His His
370
<210> 194
<211> 429
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 194
Met Pro Phe Pro Asp Leu Ile Gln Pro Glu Leu Gly Ala Tyr Val Ser
1 5 10 15
Ser Val Gly Met Pro Asp Asp Phe Ala Gln Phe Trp Thr Ser Thr Ile
20 25 30
Ala Glu Ala Arg Gln Ala Gly Gly Glu Val Ser Ile Val Gln Ala Gln
35 40 45
Thr Thr Leu Lys Ala Val Gln Ser Phe Asp Val Thr Phe Pro Gly Tyr
50 55 60
Gly Gly His Pro Ile Lys Gly Trp Leu Ile Leu Pro Thr His His Lys
65 70 75 80
Gly Arg Leu Pro Leu Val Val Gln Tyr Ile Gly Tyr Gly Gly Gly Arg
85 90 95
Gly Leu Ala His Glu Gln Leu His Trp Ala Ala Ser Gly Phe Ala Tyr
100 105 110
Phe Arg Met Asp Thr Arg Gly Gln Gly Ser Asp Trp Ser Val Gly Glu
115 120 125
Thr Ala Asp Pro Val Gly Ser Thr Ser Ser Ile Pro Gly Phe Met Thr
130 135 140
Arg Gly Val Leu Asp Lys Asn Asp Tyr Tyr Tyr Arg Arg Leu Phe Thr
145 150 155 160
Asp Ala Val Arg Ala Ile Asp Ala Leu Leu Gly Leu Asp Phe Val Asp
165 170 175
Pro Glu Arg Ile Ala Val Cys Gly Asp Ser Gln Gly Gly Gly Ile Ser
180 185 190
Leu Ala Val Gly Gly Ile Asp Pro Arg Val Lys Ala Val Met Pro Asp
195 200 205
Val Pro Phe Leu Cys Asp Phe Pro Arg Ala Val Gln Thr Ala Val Arg
210 215 220
Asp Pro Tyr Leu Glu Ile Val Arg Phe Leu Ala Gln His Arg Glu Lys
225 230 235 240
Lys Ala Ala Val Phe Glu Thr Leu Asn Tyr Phe Asp Cys Val Asn Phe
245 250 255
Ala Arg Arg Ser Lys Ala Pro Ala Leu Phe Ser Val Ala Leu Met Asp
260 265 270
Glu Val Cys Pro Pro Ser Thr Val Tyr Gly Ala Phe Asn Ala Tyr Ala
275 280 285
Gly Glu Lys Thr Ile Thr Glu Tyr Glu Phe Asn Asn His Glu Gly Gly
290 295 300
Gln Gly Tyr Gln Glu Arg Gln Gln Met Thr Trp Leu Ser Arg Leu Phe
305 310 315 320
Gly Val Gly Gly Pro Gly Ser Gly Gly Ala Gly Ser Pro Gly Ser Ala
325 330 335
Gly Gly Pro Gly Ser Pro Ser Ala Gln Ser Gln Leu Pro Asp Lys His
340 345 350
Ser Gly Leu His Glu Arg Ala Pro Gln Arg Tyr Gly Pro Glu Pro Glu
355 360 365
Pro Glu Pro Glu Pro Ile Pro Glu Pro Pro Lys Glu Ala Pro Val Val
370 375 380
Ile Glu Lys Pro Lys Pro Lys Pro Lys Pro Lys Pro Lys Pro Pro Ala
385 390 395 400
His Asp His Lys Asn Gln Lys Glu Thr His Gln Arg His Ala Ala Gly
405 410 415
Ser Gly Gly Gly Gly Ser Pro His His His His His His
420 425
<210> 195
<211> 375
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 195
Met Pro Phe Pro Asp Leu Ile Gln Pro Glu Leu Gly Ala Tyr Val Ser
1 5 10 15
Ser Val Gly Met Pro Asp Asp Phe Ala Gln Phe Trp Thr Ser Thr Ile
20 25 30
Ala Glu Ala Arg Gln Ala Gly Gly Glu Val Ser Ile Val Gln Ala Gln
35 40 45
Thr Thr Leu Lys Ala Val Gln Ser Phe Asp Val Thr Phe Pro Gly Tyr
50 55 60
Gly Gly His Pro Ile Lys Gly Trp Leu Ile Leu Pro Thr His His Lys
65 70 75 80
Gly Arg Leu Pro Leu Val Val Gln Tyr Ile Gly Tyr Gly Gly Gly Arg
85 90 95
Gly Leu Ala His Glu Gln Leu His Trp Ala Ala Ser Gly Phe Ala Tyr
100 105 110
Phe Arg Met Asp Thr Arg Gly Gln Gly Ser Asp Trp Ser Val Gly Glu
115 120 125
Thr Ala Asp Pro Val Gly Ser Thr Ser Ser Ile Pro Gly Phe Met Thr
130 135 140
Arg Gly Val Leu Asp Lys Asn Asp Tyr Tyr Tyr Arg Arg Leu Phe Thr
145 150 155 160
Asp Ala Val Arg Ala Ile Asp Ala Leu Leu Gly Leu Asp Phe Val Asp
165 170 175
Pro Glu Arg Ile Ala Val Cys Gly Asp Ser Gln Gly Gly Gly Ile Ser
180 185 190
Leu Ala Val Gly Gly Ile Asp Pro Arg Val Lys Ala Val Met Pro Asp
195 200 205
Val Pro Phe Leu Cys Asp Phe Pro Arg Ala Val Gln Thr Ala Val Arg
210 215 220
Asp Pro Tyr Leu Glu Ile Val Arg Phe Leu Ala Gln His Arg Glu Lys
225 230 235 240
Lys Ala Ala Val Phe Glu Thr Leu Asn Tyr Phe Asp Cys Val Asn Phe
245 250 255
Ala Arg Arg Ser Lys Ala Pro Ala Leu Phe Ser Val Ala Leu Met Asp
260 265 270
Glu Val Cys Pro Pro Ser Thr Val Tyr Gly Ala Phe Asn Ala Tyr Ala
275 280 285
Gly Glu Lys Thr Ile Thr Glu Tyr Glu Phe Asn Asn His Glu Gly Gly
290 295 300
Gln Gly Tyr Gln Glu Arg Gln Gln Met Thr Trp Leu Ser Arg Leu Phe
305 310 315 320
Gly Val Gly Gly Pro Gly Ser Gly Gly Ala Gly Ser Pro Gly Ser Ala
325 330 335
Gly Gly Pro Gly Ser Asp Pro Thr Lys Pro Pro Arg Thr Pro Thr Ala
340 345 350
Asn Thr Ser Arg Pro His His Asn Phe Gly Ser Gly Gly Gly Gly Ser
355 360 365
Pro His His His His His His
370 375
<210> 196
<211> 418
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 196
Met Thr Lys Ile Asn Asn Trp Gln Asp Tyr Gln Gly Ser Ser Leu Lys
1 5 10 15
Pro Glu Asp Phe Asp Lys Phe Trp Asp Glu Lys Ile Asn Leu Val Ser
20 25 30
Asn His Gln Phe Glu Phe Glu Leu Ile Glu Lys Asn Leu Ser Ser Lys
35 40 45
Val Val Asn Phe Tyr His Leu Trp Phe Thr Ala Ile Asp Gly Ala Lys
50 55 60
Ile His Ala Gln Leu Ile Val Pro Lys Asn Leu Lys Glu Lys Tyr Pro
65 70 75 80
Ala Ile Leu Gln Phe His Gly Tyr His Cys Asp Ser Gly Asp Trp Val
85 90 95
Asp Lys Ile Gly Ile Val Ala Glu Gly Asn Val Val Leu Ala Leu Asp
100 105 110
Cys Arg Gly Gln Gly Gly Leu Ser Gln Asp Asn Ile Gln Thr Met Gly
115 120 125
Met Thr Met Lys Gly Leu Ile Val Arg Gly Ile Asp Glu Gly Tyr Glu
130 135 140
Asn Leu Tyr Tyr Val Arg Gln Phe Met Asp Leu Ile Thr Ala Thr Lys
145 150 155 160
Ile Leu Ser Glu Phe Asp Phe Val Asp Glu Thr Asn Ile Ser Ala Gln
165 170 175
Gly Ala Ser Gln Gly Gly Ala Leu Ala Val Ala Cys Ala Ala Leu Ser
180 185 190
Pro Leu Ile Lys Lys Val Thr Ala Thr Tyr Pro Phe Leu Ser Asp Tyr
195 200 205
Arg Lys Ala Tyr Glu Leu Gly Ala Glu Glu Ser Ala Phe Glu Glu Leu
210 215 220
Pro Tyr Trp Phe Gln Phe Lys Asp Pro Leu His Leu Arg Glu Asp Trp
225 230 235 240
Phe Phe Asn Gln Leu Glu Tyr Ile Asp Ile Gln Asn Leu Ala Pro Arg
245 250 255
Ile Lys Ala Glu Val Ile Trp Ile Leu Gly Gly Lys Asp Thr Val Val
260 265 270
Pro Pro Ile Thr Gln Met Ala Ala Tyr Asn Lys Ile Gln Ser Lys Lys
275 280 285
Ser Leu Tyr Val Leu Pro Glu Tyr Gly His Glu Tyr Leu Pro Lys Ile
290 295 300
Ser Asp Trp Leu Arg Glu Asn Gln Gly Pro Gly Ser Gly Gly Ala Gly
305 310 315 320
Ser Pro Gly Ser Ala Gly Gly Pro Gly Ser Pro Ser Ala Gln Ser Gln
325 330 335
Leu Pro Asp Lys His Ser Gly Leu His Glu Arg Ala Pro Gln Arg Tyr
340 345 350
Gly Pro Glu Pro Glu Pro Glu Pro Glu Pro Ile Pro Glu Pro Pro Lys
355 360 365
Glu Ala Pro Val Val Ile Glu Lys Pro Lys Pro Lys Pro Lys Pro Lys
370 375 380
Pro Lys Pro Pro Ala His Asp His Lys Asn Gln Lys Glu Thr His Gln
385 390 395 400
Arg His Ala Ala Gly Ser Gly Gly Gly Gly Ser Pro His His His His
405 410 415
His His
<210> 197
<211> 363
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 197
Met Thr Lys Ile Asn Asn Trp Gln Asp Tyr Gln Gly Ser Ser Leu Lys
1 5 10 15
Pro Glu Asp Phe Asp Lys Phe Trp Asp Glu Lys Ile Asn Leu Val Ser
20 25 30
Asn His Gln Phe Glu Phe Glu Leu Ile Glu Lys Asn Leu Ser Ser Lys
35 40 45
Val Val Asn Phe Tyr His Leu Trp Phe Thr Ala Ile Asp Gly Ala Lys
50 55 60
Ile His Ala Gln Leu Ile Val Pro Lys Asn Leu Lys Glu Lys Tyr Pro
65 70 75 80
Ala Ile Leu Gln Phe His Gly Tyr His Cys Asp Ser Gly Asp Trp Val
85 90 95
Asp Lys Ile Gly Ile Val Ala Glu Gly Asn Val Val Leu Ala Leu Asp
100 105 110
Cys Arg Gly Gln Gly Gly Leu Ser Gln Asp Asn Ile Gln Thr Met Gly
115 120 125
Met Thr Met Lys Gly Leu Ile Val Arg Gly Ile Asp Glu Gly Tyr Glu
130 135 140
Asn Leu Tyr Tyr Val Arg Gln Phe Met Asp Leu Ile Thr Ala Thr Lys
145 150 155 160
Ile Leu Ser Glu Phe Asp Phe Val Asp Glu Thr Asn Ile Ser Ala Gln
165 170 175
Gly Ala Ser Gln Gly Gly Ala Leu Ala Val Ala Cys Ala Ala Leu Ser
180 185 190
Pro Leu Ile Lys Lys Val Thr Ala Thr Tyr Pro Phe Leu Ser Asp Tyr
195 200 205
Arg Lys Ala Tyr Glu Leu Gly Ala Glu Glu Ser Ala Phe Glu Glu Leu
210 215 220
Pro Tyr Trp Phe Gln Phe Lys Asp Pro Leu His Leu Arg Glu Asp Trp
225 230 235 240
Phe Phe Asn Gln Leu Glu Tyr Ile Asp Ile Gln Asn Leu Ala Pro Arg
245 250 255
Ile Lys Ala Glu Val Ile Trp Ile Leu Gly Gly Lys Asp Thr Val Val
260 265 270
Pro Pro Ile Thr Gln Met Ala Ala Tyr Asn Lys Ile Gln Ser Lys Lys
275 280 285
Ser Leu Tyr Val Leu Pro Glu Tyr Gly His Glu Tyr Leu Pro Lys Ile
290 295 300
Ser Asp Trp Leu Arg Glu Asn Gln Gly Pro Gly Ser Gly Gly Ala Gly
305 310 315 320
Ser Pro Gly Ser Ala Gly Gly Pro Gly Ser Asp Pro Thr Lys Pro Pro
325 330 335
Arg Thr Pro Thr Ala Asn Thr Ser Arg Pro His His Asn Phe Gly Ser
340 345 350
Gly Gly Gly Gly Ser Pro His His His His His
355 360

Claims (11)

1.一种包含经配置形成至少两个密封室的可变形材料的套装，所述套装包含：
第一室；
第二室；和
任选其它室；
其中该套装的各室被易碎的或可撕开的一个或多个屏障分隔开，其中第一室含有包含具有过水解活性的酶的低粘度液体溶液，其中所述酶包含SEQ ID NO: 1；
其中第二室包含至少一种酰基供体底物和胶凝剂，其中所述酰基供体底物是三醋精，
其中第二室或任选其它室包含过氧化物源，和
其中所述酰基供体底物、所述胶凝剂和所述过氧化物源均呈粉末形式。
2.权利要求1的套装，其中所述具有过水解活性的酶还包含与酶的N端或C端融合的结合域，所述结合域对口腔组织具有亲和力。
3.权利要求1或权利要求2的套装，其中所述对口腔组织具有亲和力的结合域包含选自SEQ ID NO: 178-197的氨基酸序列。
4.权利要求1的套装，其中所述过氧化物源是选自以下的固体过氧化物源：过氧化脲、聚乙烯吡咯烷酮-过氧化氢复合物、过碳酸钠、过硼酸钠和金属过氧化物。
5.权利要求1的套装，其中所述胶凝剂选自卡波姆胶凝剂、多糖树胶、改性食品淀粉、基于动物的明胶、二氧化硅及其两种或更多种的组合。
6.权利要求5的套装，其中所述动物是鱼。
7.权利要求1的套装，其中所述低粘度水溶液还包含缓冲剂。
8.权利要求4的套装，其中所述金属过氧化物选自过氧化锌和过氧化钙。
9.一种组合物，其包含在存贮期间物理上与第二部分分隔开并且在临用前与第二部分混合的第一部分，其中第一部分包含具有过水解活性的酶，所述酶包含SEQ ID NO: 1；
所述第二部分包含均呈粉末形式的过氧化物源、胶凝剂和至少一种酰基供体底物，其中所述酰基供体底物是三醋精；和
其中所述组合物是多部分口腔护理组合物。
10.权利要求9的组合物，其中所述过氧化物源是选自以下的固体过氧化物源：过氧化脲、聚乙烯吡咯烷酮-过氧化氢复合物、过碳酸钠、过硼酸钠和金属过氧化物。
11.权利要求9或10的组合物，其中所述过氧化物源是过氧化脲或聚乙烯吡咯烷酮-过氧化氢复合物。
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