CN101528917A

CN101528917A - 用于制备立体异构纯的他汀类及其合成中间体的组合物和方法

Info

Publication number: CN101528917A
Application number: CNA2007800368416A
Authority: CN
Inventors: 洛林·琼吉尔; 利萨·玛丽·纽曼; 艾米丽·穆德弗; 吉伽特·W·哈思曼; 史提芬尼·J·珍妮; 朱军; 贝娜·贝洛茨安; 约翰·H·格瑞特; 詹姆士·拉伦德
Original assignee: Codexis Inc
Current assignee: Codexis Inc
Priority date: 2006-10-02
Filing date: 2007-10-01
Publication date: 2009-09-09
Anticipated expiration: 2027-10-01
Also published as: US7879585B2; US20130040364A1; EP2066788A2; CN101528917B; US20110195465A1; US20080248539A1; WO2008042876A3; EP2066788B1; US8273547B2; IL197529A0; WO2008042876A2; US8617864B2; KR20090083900A; EP2066788A4

Abstract

本发明提供了与天然存在的野生型酮还原酶相比具有改进性质的酮还原酶。还提供了编码工程酮还原酶的多核苷酸、能表达所述工程酮还原酶的宿主细胞、使用所述工程酮还原酶合成多种手性纯的化合物的方法以及由所述方法制备的手性纯的化合物。

Description

用于制备立体异构纯的他汀类及其合成中间体的组合物和方法

1.技术领域

本公开内容涉及用于立体选择性还原羟基氧代酯(hydroxy oxo ester)如5-羟基-3-氧代-己酸酯以生成立体异构纯的对应顺式二羟基酯的组合物和方法。更具体地，本公开内容涉及与衍生它们的野生型酮还原酶相比具有改进性质的非天然存在的工程酮还原酶(engineered ketoreductase)、编码所述工程酮还原酶的多核苷酸、包含此类多核苷酸的宿主细胞、使用所述工程酮还原酶合成多种立体异构纯的化合物的方法以及由所述方法合成的立体异构纯的化合物。

2.序列表、表或计算机程序的引用

依据37 C.F.R.§§1.821(c)和1.821(e)随本文同时提交的序列表的全部内容通过引用并入本文。

3.背景

立体异构纯的顺式3，5-二羟基己酸酯是用于合成降胆固醇他汀类(statins)的关键的手性中间体，所述他汀类如阿托伐他汀钙(以商标名称

由Pfizer，Inc.销售)、罗苏伐他汀钙(以商标名称

由AstraZeneca，Ltd.销售)和匹伐他汀(以商标名称Lipalo由Kowa CompanyLtd.和Nissan Chemical Industries在日本销售)。尽管已知制备这些手性中间体的多种方法，包括还原对应的5-羟基-3-氧代己酸酯的化学法和酶法，但是这些方法具有重大缺点，使它们难以成为用于商品规模合成的理想方法。鉴于这些关键的手性中间体在合成降胆固醇他汀类中的重要性，高度期望用于以经济和高效的方法合成这些化合物的组合物和方法。

4.概述

如上文提及，根据下述结构式(IIa)的立体异构纯的顺式3，5-二羟基己酸酯是合成降胆固醇他汀类(包括但不限于阿托伐他汀、罗苏伐他汀和匹伐他汀)的关键中间体：

其中X选自卤素(例如氯和溴)、氰基和-OR⁶，其中R⁶是氢或保护基团，且R¹选自(C2-C12)烃基、(C6-C10)芳基和(C7-C12)芳基烃基。这些关键的手性中间体通常通过还原根据结构式(Ia)的对应的对映体纯的5-羟基-3-氧代己酸酯而合成：

所述还原是在结构式(IIa)(见上)的顺式二羟基酯非对映体以超过结构式(IIb)的对应反式二羟基酯非对映体的非对映体过量获得的条件下进行的：

最近，已经鉴定可用于进行这种对映选择性还原的某些酮还原酶(参见例如美国专利第6,645,746号和WO 01/40450)。本发明人发现能催化上述对映选择性还原的酮还原酶可使用实验室进化技术如DNA改组而被工程化，以产生与获自酿酒酵母(Saccharomyces cerevisiae)的天然存在的野生型酮还原酶相比具有改进性质的非天然存在的工程酮还原酶。进一步地，本公开内容还提供了分离的天然存在的酮还原酶，其包括本文所公开的工程酮还原酶的突变集合中的任何一种突变。因此，包括此类突变集合的此类天然存在的酮还原酶可用于本文所公开的任何一种工艺、试剂盒、反应混合物等等。

改进的性质可涉及野生型酮还原酶的不同方面。例如，所述改进的性质可包括酶在立体选择性还原反应条件下的稳定性、酮还原酶的酶活性、和/或对抑制(例如产物抑制)的敏感性。

因此，在一个方面中，本公开内容提供了与获自酿酒酵母的天然存在的野生型酮还原酶相比具有改进性质的工程(或分离的天然存在的变体)酮还原酶。所述工程酮还原酶可具有单种改进的性质，或者它们可具有任何组合的两种或多种改进的性质。在一些方面中，所述工程酮还原酶可包括与野生型酮还原酶氨基酸序列具有至少90％、91％、92％、93％、94％、95％、96％、97％、98％或99％同一性的氨基酸序列，条件是所述工程氨基酸序列包括足以提供改进性质的一种或多种突变。

在一些实施方案中，所述工程酮还原酶与野生型酮还原酶相比具有增加的酶活性。酶活性的改进可通过使用标准酶测定比较工程酮还原酶的比活性与野生型酮还原酶的比活性来测量。改进的量的范围可从对应的野生型酮还原酶的酶活性的1.5倍到多至2倍、5倍、10倍、20倍、25倍、50倍、75倍、100倍、150倍、200倍、250倍、300倍或更多倍酶活性。在特定的实施方案中，所述工程酮还原酶显示出为比野生型酮还原酶的酶活性大1.5至50倍、1.5至100倍、1.5至150倍、1.5至200倍、1.5至250倍或1.5至300倍的范围内的改进的酶活性。酶活性的改进还包括立体选择性增加或产物抑制减少。

在一些实施方案中，所述工程酮还原酶与野生型酮还原酶相比显示改进的热稳定性。热稳定性的改进可通过比较所述工程酮还原酶在指定的温度下温育指定的时间段后保留的酶活性程度与对应的野生型酶在类似的条件下保留的酶活性程度而测量。

本文所述的工程酮还原酶可通过利用包括各种诱变和重组技术的标准实验室技术，诱变编码酵母(Saccharomyces)的天然存在的野生型酮还原酶的基因而获得。

在一些实施方案中，本文所述的工程酮还原酶具有与衍生它们的野生型酮还原酶的氨基酸序列对应的序列且包括导致酶性质改进的一种或多种氨基酸突变。在一些实施方案中，所述突变是全面改进一种或多种酶性质的突变的选定组合。在一些实施方案中，如当改进性质来自单个突变或突变的特定组合时，所述工程酮还原酶可任选地包括在多肽序列内的其他残基位置的一种或多种保守性突变。

在一些实施方案中，所述酮还原酶包括与SEQ ID NO：2对应、或与SEQ ID NO：2具有至少约90％、91％、92％、93％、94％、95％、96％、97％、98％或99％同一性的氨基酸序列，并且其中所述氨基酸序列包括相对SEQID NO：2在下述残基位置之一的至少一种突变：6、27、31、36、48、63、65、86、125、152、160、165、194、214、218、234、248、250、263、290、296、297、301和307。在一个实施方案中，在上述位置之一的至少一种突变必须是与野生型SEQ ID NO：2序列相比的非保守性突变。

在一些实施方案中，所述酮还原酶包括与SEQ ID NO：2对应、或与SEQ ID NO：2具有至少约90％、91％、92％、93％、94％、95％、96％、97％、98％或99％同一性的氨基酸序列，并且其中所述氨基酸序列包括在第63位的芳香族残基。在一个实施方案中，所述芳香族残基是色氨酸。

在一些实施方案中，所述酮还原酶具有与序列表中所列出的氨基酸序列的任何一个具有至少约80、85、90、91、92、93、94、95、96、97、98或99％同一性的氨基酸序列，条件是所述氨基酸序列与野生型序列(SEQ IDNO：2)不同。在一些实施方案中，所述酮还原酶具有与序列表中所列出的氨基酸序列的任何一个有同一性并包括一种或多种保守性突变(包括例如1、2、3、1-5、1-10、1-20或更多种保守性突变)的氨基酸序列。

在一些实施方案中，所述酮还原酶包括与SEQ ID NO：2对应、或与SEQ ID NO：2具有至少约90、91、92、93、94、95、96、97、98或99％同一性，并且包括下列特征的一种或多种的氨基酸序列：

X⁶是极性或酸性氨基酸残基；

X²⁷是脂肪族或碱性氨基酸残基；

X³¹是包含羟基的或脂肪族氨基酸残基；

X³⁶是小氨基酸残基；

X⁴⁸是碱性氨基酸残基；

X⁶³是疏水性或芳香族氨基酸；

X⁶⁵是包含羟基的或小氨基酸残基；

X⁸⁶是脂肪族或疏水性氨基酸残基；

X¹²⁵是脂肪族或芳香族氨基酸残基；

X¹⁵²是碱性氨基酸残基；

X¹⁶⁰是包含羟基的或小氨基酸残基；

X¹⁶⁵是极性或酸性氨基酸残基；

X¹⁹⁴是芳香族氨基酸或极性亲水性氨基酸残基；

X²¹⁴是极性亲水性氨基酸残基；

X²¹⁸是包含羟基的氨基酸残基；

X²³⁴是极性亲水性氨基酸残基；

X²⁴⁸是脂肪族氨基酸残基；

X²⁵⁰是碱性氨基酸残基；

X²⁶³是酸性或极性氨基酸残基；

X²⁹⁰是酸性氨基酸残基；

X²⁹⁶是脂肪族氨基酸残基；

X²⁹⁷是芳香族氨基酸残基；

X³⁰¹是脂肪族或包含羟基的或酸性或亲水性或碱性氨基酸残基；和

X³⁰⁷是芳香族、极性或包含羟基的氨基酸残基。在一个实施方案中，所述酮还原酶包括所有上述特征。在一个实施方案中，所述酮还原酶包括至少一种特征以使至少一种残基与SEQ ID NO：2相比是突变的。在一个实施方案中，所述酮还原酶包括至少一种特征以使至少一种残基与SEQ IDNO：2相比是非保守性突变的。

X⁶是极性或酸性氨基酸残基；

X²⁷是脂肪族或碱性氨基酸残基；

X³¹是包含羟基的或脂肪族氨基酸残基；

X³⁶是小氨基酸残基；

X⁴⁸是碱性氨基酸残基；

X⁶³是芳香族氨基酸；

X⁶⁵是包含羟基的或小氨基酸残基；

X⁸⁶是脂肪族或疏水性氨基酸残基；

X¹²⁵是脂肪族或芳香族氨基酸残基；

X¹⁵²是碱性氨基酸残基；

X¹⁶⁰是包含羟基的或小氨基酸残基；

X¹⁶⁵是极性或酸性氨基酸残基；

X¹⁹⁴是芳香族氨基酸或极性亲水性氨基酸残基；

X²¹⁴是极性亲水性氨基酸残基；

X²¹⁸是包含羟基的氨基酸残基；

X²³⁴是极性亲水性氨基酸残基；

X²⁴⁸是脂肪族氨基酸残基；

X²⁵⁰是碱性氨基酸残基；

X²⁶³是酸性或极性氨基酸残基；

X²⁹⁰是酸性氨基酸残基；

X²⁹⁶是脂肪族氨基酸残基；

X²⁹⁷是芳香族氨基酸残基；

在一些实施方案中，所述酮还原酶包括与SEQ ID NO：2的酮还原酶相比具有改进的活性并且具有下述氨基酸序列的酮还原酶，所述氨基酸序列与图3的野生型序列酮还原酶(SEQ ID NO：2)对应并包括选自以下的一种或多种突变：R27A、R27K、N31S、A36V、Y48H、163W、R65G、R65S、L86I、F125L、K152R、A160T、Y194C、A218T、V248I、K250R、E290D、L296V、Y297W、Y297F、L301K、L301R、L301A、L301S、L301E、L301P、L301Q、L301V、L301T、L301Y、L301D、Y307H、Y307N和Y307S。在一些实施方案中，此类改进的工程酮还原酶包括与SEQ ID NO：2具有至少90％、91％、92％、93％、94％、95％、96％、97％、98％或99％同一性的氨基酸序列，条件是所述氨基酸序列包括至少一种或多种上文列出的突变(在一些实施方案中，至少2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20或更多种突变)。

在一些实施方案中，所述工程酮还原酶包括具有改进的酶稳定性并具有下述氨基酸序列的酮还原酶，所述氨基酸序列与图3的野生型序列(SEQID NO：2)对应并包括选自以下的一种或多种突变：E44D、I46L、I55V、I56V、A60T、I63V、L76M、G103S、L106I、D114G、L121I、Q144R、S148T、N158H、Q223H、I237G、I237N、I237R、S239T、V253A。

在一些实施方案中，所述工程酮还原酶包括具有改进的酶活性和改进的酶稳定性的组合并且具有下述氨基酸序列的酮还原酶，所述氨基酸序列与图3的野生型序列(SEQ ID NO：2)对应并包括选自以下的一种或多种突变：Q6E、N31P、A160S、Q165E、Q214H、Q214R、E234Q、Q263E。在一个实施方案中，所述酮还原酶包括所有这些突变。

在一些实施方案中，所述工程酮还原酶包括具有改进的酶活性和/或改进的酶稳定性的组合并且具有下述氨基酸序列的酮还原酶，所述氨基酸序列与图3的野生型序列(SEQ ID NO：2)对应并包括选自以下的一种或多种突变：N40Y、V43L、K51E、I58V、E62Q、A73P、K79R、K152Q、K169E、F185I、Q189H、G192D、H200L、D201G、K215E、K215M、K216R、D221V、S233C、I237D、K250E、I265V、L287R、K304R、Q310R、K311E、V312S、V312E。

此类工程酮还原酶的具体示例性实施方案包括SEQ ID NO：16、18、20、22、24、26、28、30、32、34、36、38、40、42、44、46、48、50、52、54、56、58、60、62、64、66、68、70、72、74、76、78、80、82、84、86、88、90、92、94、96、98、100、102、104、106、108、110、112、114、116、118、120、122、124、126、128、130、132、134、136、138、140、142、144、146、148、150、152、154、156、158、160、162、164、166、168、170、172、174、176、178、180、182、184、186、188、190、192、194、196、198、200、202、204、206、208、210、212、214、216、218、220、222、224、226、228、230、232、234、236、238、240、242、244、246、248、250、252、254、256、258、260、262、266、268、270、272、274、276、278、280、282、284、286、288、290、292、294、296、298、300、302、304、306、308、310、312、314、316、318、320、322、324、326、328、330、332、334、336、338、340、342、344、346、348、350、352、354、356、358、360、362、364和366。

在一些实施方案中，所述工程酮还原酶具有与表1所列出的氨基酸序列具有至少约80、85、90、91、92、93、94、95、96、97、98或99％同一性的氨基酸序列。

在一些实施方案中，所述酮还原酶包括与SEQ ID NO：316或318具有至少约95、96、97、98或99％同一性的氨基酸序列。在一个实施方案中，所述酮还原酶包括SEQ ID NO：316或318的氨基酸序列，但是所述氨基酸序列在与SEQ ID NO：2相比未突变的残基处具有一种或多种保守性突变(包括1、2、3、4、5、6、7、8、9、10或更多种)。

在另一个方面中，本公开内容提供了编码本文所述的工程酮还原酶的多核苷酸或在高严格条件下与此类多核苷酸杂交的多核苷酸。所述多核苷酸可包括用于表达被编码的工程酮还原酶的启动子和其他调节元件，并可利用针对具体期望的表达系统优化的密码子。

在又一个方面中，本公开内容提供了包括本文所述的多核苷酸和/或表达载体的宿主细胞。所述宿主细胞可以是所述工程酮还原酶源自的酿酒酵母，或者它们可以是不同的生物体。所述宿主细胞可用于表达和分离本文所述的工程酮还原酶，或者可选择地，它们可用于下文进一步描述的各种方法。

所述酮还原酶可用于以高产率和高立体选择性程度将结构式(Ia)的羟基氧代酯对映体还原为其对应的顺式二羟基物(dihydroxys)。

在一个方面中，所述酮还原酶以纯化的或分离的形式使用。在另一个方面中，使用来自表达所述酶的细胞的提取物。

因此，在另一个方面中，本公开内容提供了制备根据结构式(IIa)的顺式二羟基酯的方法：

其中X和R¹如前文所定义。所述方法通常包括选择性还原根据结构式(Ia)的羟基氧代酯对映体：

其中X和R¹如对结构式(IIa)所定义，所述还原使用本文所述的工程酮还原酶。所述方法可使用表达工程酮还原酶的全细胞(如本文所述的宿主细胞)、这类细胞的提取物或溶解产物、或纯化的工程酮还原酶来进行。

如熟练的技术人员所理解，上文示例的还原反应通常需要辅因子(通常为NADH或NADPH)和用于再生辅因子的系统(如葡萄糖和葡萄糖脱氢酶)。因为细胞通常提供了此类辅因子和辅因子再生系统，所以在使用全细胞细胞提取物或细胞溶解产物的实施方案中，加入此类辅因子和辅因子再生系统可以是不必要的。在使用纯化的工程酮还原酶的实施方案中，此类辅因子和任选地此类辅因子再生系统通常与羟基氧代酯底物和酮还原酶一起被添加到反应介质中。如工程酮还原酶一样，包括辅因子再生系统的任何酶均可以以此类细胞的提取物或溶解产物的形式、或作为纯化的酶添加于反应混合物。在使用细胞提取物或细胞溶解产物的实施方案中，用于产生所述提取物或溶解产物的细胞可被工程化为表达包括单独或与工程酮还原酶一起的辅因子再生系统的酶。在使用全细胞的实施方案中，所述细胞可被工程化为表达同时包括辅因子再生系统和工程酮还原酶的酶。

不论用全细胞、细胞提取物还是用纯化的酮还原酶进行所述方法，可使用单个酮还原酶，或可选地，可使用两种或多种酮还原酶的混合物。

本文所述的酮还原酶对结构式(Ia)的对映体具有高特异性并且以高产率和高立体选择性程度催化上述的还原反应。根据所用的特定工程酮还原酶，可容易地实现约80至99.9％范围的产率，其中非对映体过量(“d.e.”)≥99.5％。例如，已经发现本公开内容的工程酮还原酶可用于将结构式(Ia)(见上)的5-羟基氧代酯对映体立体选择性地还原为对应的结构式(IIa)的顺式二羟基物，其中产率范围为90至99.9％并且立体选择性程度为≥99.7％。

在很多实施方案中，可实现≥99.8％、99.9％、99.91％、99.92％、99.93％、99.94％、99.5％、99.96％、99.97％、99.98％且甚至99.99％d.e.的非对映选择性。实际上，如下文与图6和7结合更详细地论述，使用SEQ ID NO：316的工程酮还原酶由以结构式(Ia)的对映体＞99％纯的起始底物获得的未纯化的粗还原产物是以结构式(IIa)的顺式非对映体＞99.99％纯的。

因为本文所述的工程酮还原酶具有如此高的立体选择性，所以获得的结构式(IIa)的顺式二羟基酯可以以大致立体化学纯的形式回收，而不需要将它与对应的反式非对映体或任何其他的非对映体手性分离。实际上，由于所述反应的高产率和高立体选择性，因此如果结构式(I)的羟基氧代酯底物是以结构式(Ia)的对映体大致纯的，那么特定的结构式(IIa)的顺式二羟基酯非对映体可在不纯化的情况下以大致纯的或纯的非对映体从反应介质中回收。

结构式(IIa)的手性二羟基酯可用作合成降胆固醇他汀类的起始物质，所述降胆固醇他汀类包括但不限于阿托伐他汀、罗苏伐他汀和匹伐他汀。很多这些方法的关键步骤是保护结构式(IIa)的顺式二羟基酯的羟基基团，产生根据结构式(IIIa)的受保护的顺式二羟基酯：

其中X和R¹如前文对结构式(IIa)所定义，并且每个R²是保护基团或者可选地，两个R²基团可一起形成取代的或未取代的亚烃基桥。在一些实施方案中，所述受保护的顺式二羟基酯是根据结构式(IVa)的化合物：

其中X和R¹如前文对结构式(IIa)所定义，并且R³和R⁴各自彼此独立地选自氢、(C1-C12)烃基、(C6-C10)芳基和(C7-C12)芳基烃基，或可选地，R³与R⁴一起形成(C4-C10)环烃基或杂环烃基。在特定的实施方案中，R³与R⁴各为甲基。

在一些实施方案中，所述受保护的顺式二羟基酯是根据结构式(Va)的化合物：

其中X和R¹如前文对结构式(IIa)所定义，并且R⁵选自(C1-C12)烃基、(C6-C10)芳基和(C7-C12)芳基烃基。在一些实施方案中，R⁵是苯基。

由于本文所述的工程酮还原酶的立体选择性，它们可用于合成根据结构式(IIIa)、(IVa)和(Va)的受保护的顺式二羟基酯的立体异构纯的制品。所述方法通常包括使用如本文所述的工程酮还原酶对映选择性地还原根据结构式(Ia)(见上)的羟基氧代酯对映体，以产生包括根据结构式(IIa)(见上)的顺式二羟基酯的第一反应产物，以及保护顺式二羟基酯的羟基基团以产生结构式(IIIa)的受保护的顺式二羟基酯。由于所述工程酮还原酶的高立体选择性，结构式(IIIa)的受保护的顺式二羟基酯可在不进行手性分离的情况下以大致立体化学纯的或纯的非对映体回收，即基本上不含对应的反式非对映体和任何其他非对映体。

所述顺式二羟基酯和/或受保护的顺式二羟基酯可用作合成降胆固醇他汀类的已知方法的反应物。用于制备示例性他汀类的示例性合成途径如图8、9和10所示。因此，在另一个方面中，本公开内容提供了制备他汀类的大致立体异构纯的制品的方法，所述他汀类如，例如阿托伐他汀、罗苏伐他汀和匹伐他汀。所述方法通常包括：(i)用本文所述的工程酮还原酶还原大致对映体纯的根据结构式(Ia)的羟基氧代酯对映体：

其中R¹和X如前文所定义，以产生包括大致非对映体纯的根据结构式(IIa)的顺式二羟基酯的第一反应产物：

其中X和R¹如对结构式(Ia)所定义；以及(ii)此后使用结构式(IIa)的顺式二羟基酯以合成他汀类。因为本文所述的工程酮还原酶以高对映选择性程度催化步骤(i)的还原，所以结构式(IIa)的顺式二羟基酯可用于合成具有高度立体异构体纯度的他汀类，所述合成使用在接近室温下进行的反应，并且不需要手性分离。实际上，还原反应的高度立体选择性允许以高产率容易且经济地制备％d.e.在羟基氧代酯起始底物％e.e.的约90至99.99％内的他汀类。

5.附图简述

图1示例了酮还原酶和卤代醇脱卤素酶(halohydrogen dehalogenases)在将4-卤素-3-氧代丁酸烃基酯转化为用于合成他汀类的各种中间体中的作用。

图2示例了用于从3，5-二羟基-6-卤代己酸叔丁酯合成(6R)-(2-氰乙基)-2，2二甲基-1，3-二噁烷叔丁酯(t-butyl(6R)-(2-cyanoethyl)-2，2dimethyl-1，3-dioxane)的各种途径。

图3提供了由来自酿酒酵母的Ydll24wp基因(Genbank登录号：NP 010159.1；GI：6320079)编码的酮还原酶的野生型序列(SEQ ID NO：2)。

图4提供了来自酿酒酵母的酮还原酶的氨基酸序列，其中标记的残基可被修饰以生成具有改进的酮还原酶性质的工程多肽。

图5提供了质粒pCK110900的示例，其中克隆的酮还原酶基因可操作地连接至处于lacI抑制子控制下的lac启动子以表达工程酮还原酶。

图6显示了实施例27的6-氰基-(3R，5R)-二羟基己酸叔丁酯样品(由本文所述的方法的实施方案制备的样品)(上图)和由商品化晶体(6R)-(2-氰乙基)-2，2-二甲基-1，3-二噁烷-(4R)-乙酸叔丁酯制备的样品(下图)的LC/MS/MS色谱图。

图7显示了实施例28的(6R)-(2-氰乙基)-2，2二甲基-1，3-二噁烷-(4R)-乙酸叔丁酯样品(由本发明的方法制备的样品)和商品化晶体样品的GC/MS色谱图。

图8示例了罗苏伐他汀的合成流程；R表示H或合适的保护基团。

图9示例了匹伐他汀的合成流程；R表示H或合适的保护基团。

图10示例了阿托伐他汀的合成流程；R表示H或合适的保护基团。

6.详述

6.1定义

如本文所用，下列术语意在具有下列含义：

“烃基(alkyl)”单独或作为另一个取代基的部分是指通过从母体烷烃(alkane)、烯烃(alkene)或炔烃的单个碳原子消除一个氢原子而得到的具有规定数目的碳原子(即C1-C6是指1至6个碳原子)的饱和或不饱和的支链、直链或环状一价烃基。典型的烃基基团包括但不限于甲基；乙基类如乙烷基、乙烯基、乙炔基；丙基类如丙烷-1-基、丙烷-2-基、环丙烷-1-基、丙-1-烯-1-基、丙-1-烯-2-基、丙-2-烯-1-基、环丙-1-烯-1-基；环丙-2-烯-1-基、丙-1-炔-1-基、丙-2-炔-1-基等；丁基类如丁烷-1-基、丁烷-2-基、2-甲基-丙烷-1-基、2-甲基-丙烷-2-基、环丁烷-1-基、丁-1-烯-1-基、丁-1-烯-2-基、2-甲基-丙-1-烯-1-基、丁-2-烯-1-基、丁-2-烯-2-基、丁-1，3-二烯-1-基、丁-1，3-二烯-2-基、环丁-1-烯-1-基、环丁-1-烯-3-基、环丁-1，3-二烯-1-基、丁-1-炔-1-基、丁-1-炔-3-基、丁-3-炔-1-基等；及类似烃基。在意指特定的饱和度时，使用名称“烷基(alkanyl)”、“烯基(alkenyl)”和/或“炔基”，如下文所定义。“低级烃基”是指含有1至6个碳原子的烃基基团。

“烷基”单独或作为另一个取代基的部分是指通过从母体烷烃的单个碳原子消除一个氢原子而得到的饱和的支链、直链或环状烃基。典型的烷基基团包括但不限于甲烷基；乙烷基；丙烷基类如丙烷-1-基、丙烷-2-基(异丙基)、环丙烷-1-基等；丁烷基类如丁烷-1-基、丁烷-2-基(仲丁基)、2-甲基-丙烷-1-基(异丁基)、2-甲基-丙烷-2-基(叔丁基)、环丁烷-1-基等；及类似烷基。

“烯基”单独或作为另一个取代基的部分是指通过从母体烯烃的单个碳原子消除一个氢原子而得到的具有至少一个碳碳双键的不饱和的支链、直链或环状烃基。所述基团可以是关于双键的顺式或反式构象。典型的烯基基团包括但不限于乙烯基；丙烯基类如丙-1-烯-1-基、丙-1-烯-2-基、丙-2-烯-1-基、丙-2-烯-2-基、环丙-1-烯-1-基；环丙-2-烯-1-基；丁烯基类如丁-1-烯-1-基、丁-1-烯-2-基、2-甲基-丙-1-烯-1-基、丁-2-烯-1-基、丁-2-烯-2-基、丁-1，3-二烯-1-基、丁-1，3-二烯-2-基、环丁-1-烯-1-基、环丁-1-烯-3-基、环丁-1，3-二烯-1-基等；及类似烯基。

“炔基”单独或作为另一个取代基的部分是指通过从母体炔烃的单个碳原子消除一个氢原子而得到的具有至少一个碳碳三键的不饱和的支链、直链或环状烃基。典型的炔基基团包括但不限于乙炔基；丙炔基类如丙-1-炔-1-基、丙-2-炔-1-基等；丁炔基类如丁-1-炔-1-基、丁-1-炔-3-基、丁-3-炔-1-基等；及类似炔基。

“烃基二基(Alkyldiyl)”单独或作为另一个取代基的部分是指通过从母体烷烃、烯烃或炔烃的两个不同的碳原子各消除一个氢原子或通过从母体烷烃、烯烃或炔烃的单个碳原子消除两个氢原子而得到的具有规定数目的碳原子(即C1-C6表示1至6个碳原子)的饱和或不饱和的支链、直链或环状二价烃基。两个一价基团中心或二价基团中心的每个化合价可与相同或不同的原子形成键。典型的烃基二基基团包括但不限于甲烷二基(methandiyl)；乙基二基类(ethyldiyls)如乙烷-1，1-二基、乙烷-1，2-二基、乙烯-1，1-二基、乙烯-1，2-二基；丙基二基类(propyldiyls)如丙烷-1，1-二基、丙烷-1，2-二基、丙烷-2，2-二基、丙烷-1，3-二基、环丙烷-1，1-二基、环丙烷-1，2-二基、丙-1-烯-1，1-二基、丙-1-烯-1，2-二基、丙-2-烯-1，2-二基、丙-1-烯-1，3-二基、环丙-1-烯-1，2-二基、环丙-2-烯-1，2-二基、环丙-2-烯-1，1-二基、丙-1-炔-1，3-二基等；丁基二基类(butyldiyls)如丁烷-1，1-二基、丁烷-1，2-二基、丁烷-1，3-二基、丁烷-1，4-二基、丁烷-2，2-二基、2-甲基-丙烷-1，1-二基、2-甲基-丙烷-1，2-二基、环丁烷-1，1-二基；环丁烷-1，2-二基、环丁烷-1，3-二基、丁-1-烯-1，1-二基、丁-1-烯-1，2-二基、丁-1-烯-1，3-二基、丁-1-烯-1，4-二基、2-甲基-丙-1-烯-1，1-二基、2-亚甲烷基(methanylidene)-丙烷-1，1-二基、丁-1，3-二烯-1，1-二基、丁-1，3-二烯-1，2-二基、丁-1，3-二烯-1，3-二基、丁-1，3-二烯-1，4-二基、环丁-1-烯-1，2-二基、环丁-1-烯-1，3-二基、环丁-2-烯-1，2-二基、环丁-1，3-二烯-1，2-二基、环丁-1，3-二烯-1，3-二基、丁-1-炔-1，3-二基、丁-1-炔-1，4-二基、丁-1，3-二炔-1，4-二基等；及类似烃基二基。在意指特定的饱和度时，使用名称烷基二基(alkanyldiyl)、烯基二基(alkenyldiyl)和/或炔基二基(alkynyldiyl)。在特别意指两个化合价在同一碳原子上时，使用名称“亚烃基(alkylidene)”。“低级烃基二基”是含有1至6个碳原子的烃基二基基团。在一些实施方案中，所述烃基二基基团是饱和的非环烷基二基基团，其中所述基团中心是在末端碳上，如甲烷二基(桥亚甲烷基(methano))；乙烷-1，2-二基(桥亚乙烷基(ethano))；丙烷-1，3-二基(桥亚丙烷基(propano))；丁烷-1，4-二基(桥亚丁烷基(butano))；及类似饱和的非环烷基二基(也被称为亚烃基(alkylene)，如下文所定义)。

“亚烃基”单独或作为另一个取代基的部分是指通过从直链母体烷烃、烯烃或炔烃的两端碳原子中的每个消除一个氢原子而得到的具有两个末端一价基团中心的直链饱和或不饱和的烃基二基基团。特定亚烃基中的双键或三键(如果存在)的位次在方形括号中显示。典型的亚烃基基团包括但不限于亚甲基(桥亚甲基)；亚乙基类如桥亚乙烷基、桥亚乙烯基、桥亚乙炔基；亚丙基类如桥亚丙烷基、桥亚丙[1]烯基、桥亚丙[1，2]二烯基、桥亚丙[1]炔基等；亚丁基类如桥亚丁烷基、桥亚丁[1]烯基、桥亚丁[2]烯基、桥亚丁[1，3]二烯基、桥亚丁[1]炔基、桥亚丁[2]炔基、桥亚丁[1，3]二炔基等；及类似基团。在意指特定的饱和度时，使用名称桥亚烷基(alkano)、桥亚烯基(alkeno)和/或桥亚炔基(alkyno)。在一些实施方案中，亚烃基基团是(C1-C6)或(C1-C3)亚烃基。在一些实施方案中，所述亚烃基基团是直链饱和的桥亚烷基基团，如桥亚甲烷基、桥亚乙烷基、桥亚丙烷基、桥亚丁烷基及类似桥亚烷基。

“环烃基”单独或作为另一个取代基的部分是指“烃基”基团的环状形式。典型的环烃基基团包括但不限于环丙基；环丁基类如环丁烷基和环丁烯基；环戊基类如环戊烷基和环戊烯基；环己基类如环己烷基和环己烯基；及类似环烃基。

“母体芳香族环系统”是指具有共轭π电子系统的不饱和的环或多环系统。特别包括在“母体芳香族环系统”的定义中的有稠环系统，其中一个或多个环是芳香族的并且一个或多个环是饱和或不饱和的，所述稠环系统如例如芴、茚满、茚、非那烯(phenalene)、四氢化萘等。典型的母体芳香族环系统包括但不限于醋蒽烯、苊烯、醋菲烯、蒽、薁、苯、屈(chrysene)、蒄、荧蒽、芴、并六苯、己芬、己搭烯(hexalene)、引达省(indacene)、对称引达省、茚满、茚、萘、并八苯(octacene)、辛芬(octaphene)、辛搭烯(octalene)、卵苯、戊-2，4-二烯、并五苯、并环戊二烯、戊芬(pentaphene)、苝、非那烯、菲、苉、七曜烯(pleiadene)、芘、吡蒽(pyranthrene)、玉红省(rubicene)、四氢化萘、三亚苯、三亚萘及类似母体芳香族环系统。

“芳基”单独或作为另一个取代基的部分是指通过从母体芳香族环系统的单个碳原子消除一个氢原子而得到的具有规定数目的碳原子(即C6-C10表示5至15个碳原子)的一价芳香族烃基。典型的芳基基团包括但不限于由以下衍生的基团：醋蒽烯、苊烯、醋菲烯、蒽、薁、苯、屈、蒄、荧蒽、芴、并六苯、己芬、己搭烯、不对称引达省、对称引达省、茚满、茚、萘、并八苯、辛芬、辛搭烯、卵苯、戊-2，4-二烯、并五苯、并环戊二烯、戊芬、苝、非那烯、菲、苉、七曜烯、芘、吡蒽、玉红省、三亚苯、三亚萘及类似母体芳香族环系统、和其各种氢异构体。在一些实施方案中，所述芳基基团是(C6-C10)。特定的实例是苯基和萘基。

“芳基烃基”单独或作为另一个取代基的部分是指其中与碳原子(通常末端或sp³碳原子)连接的一个氢原子被芳基基团取代的非环状烃基基团。典型的芳基烃基基团包括但不限于苄基、2-苯乙烷-1-基、2-苯乙烯-1-基、萘甲基、2-萘乙烷-1-基、2-萘乙烯-1-基、萘并苄基、2-萘并苯乙烷-1-基及类似芳烃基。在意指特定的饱和或不饱和的烃基部分时，使用名称芳基烷基、芳基烯基(arylakenyl)和/或芳基炔基。在一些实施方案中，所述芳基烃基基团是(C7-C12)芳基烃基。在特定的实施方案中，所述芳基烃基基团的烷基、烯基或炔基部分是(C1-C2)并且所述芳基部分是(C6-C10)。

本文可互换使用的“酮还原酶”和“KRED”是指能够对映选择性地还原5-羟基-3-氧代己酸酯对映体的3-氧代基团以产生对应的顺式3，5-二羟基己酸酯的多肽。所述多肽通常利用辅因子还原型烟酰胺腺嘌呤二核苷酸(NADH)或还原型烟酰胺腺嘌呤二核苷酸磷酸(NADPH)作为还原剂。如本文所用的酮还原酶包括天然存在的(野生型)酮还原酶和由人操作产生的非天然存在的工程多肽。

“编码序列”是指编码蛋白质的氨基酸序列的核酸部分(例如基因)。

“天然存在的”或“野生型”是指在自然界中发现的形式。例如，天然存在的或野生型多肽或多核苷酸序列是可从自然来源中分离并且未通过人操作有意修饰的存在于生物体中的序列。

“重组体”在用于指例如细胞、核酸或多肽时，指已用未存在于自然界的方式进行改进的材料、或者与所述材料的自然或天然形式对应的材料，或者与之相同但是由合成材料和/或通过使用重组技术的操作生成或衍生的材料、或者与所述材料的自然或天然形式对应的材料。非限制性实例包括表达未在细胞的天然(非重组)形式中发现的基因或表达另外地以不同水平表达的天然基因的重组细胞以及其他重组体。

本文可互换使用的“序列同一性的百分比”和“同源性百分比”是指多核苷酸之间和多肽之间的比较，并且通过在比较窗(comparison window)中比较两个最佳比对的序列来确定，其中所述多核苷酸或多肽序列在比较窗中的部分与用于两个序列的最佳比对的参考序列(其不包括添加或缺失)相比可包括添加或缺失(即缺口)。所述百分比可通过以下来计算：确定相同的核酸碱基或氨基酸残基出现于两个序列的位置数以得出匹配位置数，然后用所述匹配位置数除以比较窗中的位置总数并将结果乘以100以得出序列同一性的百分比。可选地，所述百分比可通过以下来计算：确定相同的核酸碱基或氨基酸残基出现于两个序列或者核酸碱基或氨基酸残基与缺口比对的位置数以得出匹配位置数，然后用所述匹配位置数除以比较窗中的位置总数并将结果乘以100以得出序列同一性的百分比。本领域技术人员理解有很多可用于比对两个序列的成熟算法。例如用于比较的序列最佳比对可通过Smith和Waterman，1981，Adv.Appl.Math.2：482的局部同源性算法、通过Needleman和Wunsch，1970，J.Mol.Biol.48：443的同源性比对算法、通过Pearson和Lipman，1988，Proc.Natl.Acad.Sci.USA 85：2444的相似性搜索方法、通过计算机化实现这些算法(GCG Wisconsin软件包中的GAP、BESTFIT、FASTA和TFASTA)或者通过视觉检查(通常参见CurrentProtocols in Molecular Biology(分子生物学最新方案)，F.M.Ausubel等人编，Current Protocols(最新方案)，Greene Publishing Associates，Inc.和JohnWiley & Sons，Inc.之间的联合投资(1995增补)(Ausubel))进行。适合于确定百分比序列同一性和序列相似性的算法的实例是BLAST和BLAST 2.0算法，它们分别在Altschul等人，1990，J.Mol.Biol.215：403-410和Altschul等人，1977，Nucleic Acids Res.3389-3402中描述。用于进行BLAST分析的软件可通过美国国家生物技术信息中心网站公开得到。这种算法包括首先通过识别查询序列中长度W的短字来识别高分值序列对(HSP)，所述短字当与数据库序列中相等长度的字比对时匹配或满足某些正阈值分值T。T被称为邻近字分值阈值(Altschul等人，见上)。这些初始的邻近字匹配字串(hit)用作启动搜索以发现包含它们的更长HSP的种子(seed)。然后沿着每个序列以两个方向延伸字匹配字串，直至不可增加累积比对分值。对于核苷酸序列，累积分值使用参数M(匹配残基对的奖分值；总是＞0)和N(错配残基的罚分值；总是＜0)来计算。对于氨基酸序列，使用分值矩阵计算累积分值。当出现以下情况时，则字匹配字串在每个方向的延伸停止：累积比对分值从其最大达到值减少X量；由于一个或多个负分值残基比对的累积，所以累积分值变为零或零以下；或者到达任一个序列的末端。BLAST算法参数W、T和X确定比对的敏感性和速度。BLASTN程序(对于核苷酸序列)默认使用字长(W)11、期望值(E)10、M＝5、N＝-4和两链的比较。对于氨基酸序列，BLASTP程序默认使用字长(W)3、期望值(E)10和BLOSUM62分值矩阵(参见Henikoff和Henikoff，1989，Proc Natl Acad Sci USA89：10915)。序列比对和％序列同一性的示例性确定可应用GCG Wisconsin软件包(Accelrys，Madison WI)中的BESTFIT或GAP程序，并使用所提供的默认参数。

“参考序列”是指用作序列比较基础的确定序列。参考序列可以是较大序列的子集，例如全长基因或多肽序列的区段。一般来说，参考序列是至少20个核苷酸或氨基酸残基长、至少25个残基长、至少50个残基长、或者核酸或多肽的全长。由于两个多核苷酸或多肽可各自(1)包括在所述两个序列之间相似的序列(即全序列的一部分)、并且(2)可进一步包括在所述两个序列之间差异的序列，因此两个(或更多个)多核苷酸或多肽之间的序列比较通常通过在“比较窗”内比较两个多核苷酸的序列以鉴定和比较局部区域的序列相似性而进行。

“比较窗”是指至少约20个邻接的核苷酸位置或氨基酸残基的概念性区段，其中序列可与至少20个邻接的核苷酸或氨基酸的参考序列比较并且其中比较窗中的序列部分与参考序列(其不包括添加或缺失)相比可包括20％或更少的添加或缺失(即缺口)以达到所述两个序列的最佳比对。所述比较窗可比20个邻接的残基更长，并且包括任选地30、40、50、100个或更长的窗。

“大致的同一性”是指在至少20个残基位置的比较窗内、通常在至少30-50个残基的窗内与参考序列相比具有至少80％序列同一性、至少85％同一性和89至95％序列同一性、更通常至少99％序列同一性的多核苷酸或多肽序列，其中所述序列同一性的百分比通过在比较窗内比较参考序列与包括总计为参考序列的20％或更少的缺失或添加的序列来计算。在应用于多肽的特定实施方案中，术语“大致的同一性”表示两个多肽序列当进行最佳比对(如通过程序GAP或BESTFIT，使用默认缺口权重)时，共有至少80％序列同一性、优选至少89％序列同一性、至少95％序列同一性或更多(例如99％序列同一性)。优选地，不相同的残基位置的不同在于保守性氨基酸置换。

“立体选择性”是指一个立体异构体与另一个立体异构体相比在化学反应或酶反应中的优先形成。立体选择性可以是部分的，其中一个立体异构体的生成与另一个相比是有利的，或者其可以是完全的，其中仅生成一个立体异构体。当这些立体异构体是对映体时，立体选择性称作对映选择性，即一个对映体在两者总数中的分数(通常报道成百分比)。它在本领域一般报道(通常为百分比)成根据式[主要对映体-次要对映体]/[主要对映体+次要对映体]从中计算的对映体过量。当立体异构体为非对映异构体时，立体选择性被称为非对映选择性，即一个非对映体在与其他非对映体的总数中的分数(通常报道成百分比)。在本公开内容的环境中，非对映选择性是指转化成结构式IIa的顺式二羟基酯(与式IIb的反式二羟基酯相反)的结构式(Ia)的羟基氧代酯的分数(通常报道成百分比)。它还可报道(通常为百分比)成根据式[顺式IIa-反式IIb]/[顺式IIa+反式IIb]从中计算的非对映体过量。

6.2酮还原酶

本公开内容提供了能对映选择性地还原5-羟基-3-氧代己酸酯对映体的3-氧代基团以产生对应的顺式3，5-二羟基己酸酯，并且当与获自酿酒酵母的天然存在的野生型KRED酶相比时具有至少一种改进性质的工程酮还原酶(“KRED”)。如上所述，由酮还原酶产生的立体异构纯的顺式3，5-二羟基己酸酯可用作合成数个降胆固醇他汀类的中间体。各种酶性质的改进可促进这些工程酮还原酶在这种中间体化合物的大规模生产中的使用。酶性质的任何数量的改进如酶活性、热稳定性和减少的辅因子需求都可用于所述的应用。

具有改进性质的酮还原酶可通过使编码酿酒酵母的酮还原酶的遗传物质突变并鉴定表达具有期望性质的工程酶的多核苷酸而获得。这些非天然存在的酮还原酶可通过各种众所周知的技术如体外诱变或定向进化而产生。在一些实施方案中，定向进化是用于产生工程酶的有吸引力的方法，因为其相对容易在整个编码多肽的全基因产生突变以及提供采用先前变异的多核苷酸并且使它们经受另外诱变和/或重组的循环以获得所选酶性质的进一步改进的能力。使全基因经受诱变可减少由于将变化限制在基因的有限区域而产生的偏好性。它还可增强在不同的酶性质方面受到影响的酶的产生，因为酶的远间隔部分可在酶功能的各种方面中起作用。用于本文目的的诱变和定向进化技术在以下文献中详细描述：Ling等人，1997，“Approaches to DNA mutagenesis：an overview(DNA诱变方法综述)”Anal.Biochem.254(2)：157-78；Dale等人，1996，“Oligonucleotide-directed randommutagenesis using the phosphorothioate method(使用硫代磷酸酯方法的寡核苷酸指导的随机诱变)”Methods Mol.Biol.57：369-74；Smith，1985，“In vitromutagenesis(体外诱变)”Ann.Reb.Genet.19：423-462；Botstein等人，1985，“Strategies and applications of in vitro mutagenesis(体外诱变的策略和应用)”Science 229：1193-1201；Carter，1986，“Site-directed mutagenesis(定点诱变)”Biochem.J.237：1-7；Kramer等人，1984，“Point Mismatch Repair(点错配修复)”Cell，38：879-887；Wells等人，1985，“Cassette mutagenesis：an efficientmethod for generation of multiple mutations at defined sites(盒式诱变：用于在确定位点产生多重突变的有效方法)”Gene 34：315-323；Minshull等人，1999，“Protein evolution by molecular breeding(经分子育种的蛋白进化)”Curr Opin Chem Biol 3：284-290；Christians等人，1999，“Directed evolutionof thymidine kinase for AZT phosphorylation using DNA family shuffling(使用DNA家族改组的用于AZT磷酸化的胸苷激酶的定向进化)”NatureBiotech 17：259-264；Crameri等人，1998，“DNA shuffling of a family of genesfrom diverse species accelerates directed evolution(对来自不同物种的基因的家族的DNA改组加速了定向进化)”Nature 391：288-291；Crameri等人，1997，“Molecular evolution of an arsenate detoxification pathway by DNAshuffling(通过DNA改组的砷酸盐解毒途径的定向进化)”Nature Biotech15：436-438；Zhang等人，1997，“Directed evolution of an effective fructosidasefrom a galactosidase by DNA shuffling and screening(通过DNA改组和筛选的从半乳糖苷酶向有效的果糖苷酶的定向进化)”Proc Natl Acad Sci USA94：45-4-4509；Crameri等人，1996，“Improved green fluorescent protein bymolecular evolution using DNA shuffling(通过使用DNA改组的分子进化改进绿色荧光蛋白)”Nature Biotech 14：315-319；Stemmer，1994，“Rapidevolution of a protein in vitro by DNA shuffling(通过DNA改组的蛋白的体外快速进化)”Nature 370：389-391；Stemmer，1994，“DNA shuffling byrandom fragmentation and reassembly：In vitro recombination for molecularevolution(通过随机断裂和重新组装的DNA改组：用于分子进化的体外重组)”Proc Natl Acad Sci USA 91：10747-10751；WO 95/22625；WO 97/0078；WO 97/35966；WO 98/27230；WO 00/42651；WO 01/75767和美国专利6,537,746。所有出版物通过引用并入本文。

编码酿酒酵母的天然存在的酮还原酶的天然存在的多核苷酸可从已知编码酮还原酶活性的分离的多核苷酸(Genbank登录号NP_010159 GI：6320079)获得。可选地，编码天然存在的酮还原酶的多核苷酸可基于已报道的编码酿酒酵母酮还原酶的基因的多核苷酸序列通过本领域已知的多核苷酸合成方法来合成。在各种实施方案中，如下文进一步描述，编码酮还原酶的天然存在的多核苷酸可被密码子优化成用于表达所述酶的特异性宿主细胞优选的密码子。例如参见实施例1。

编码天然存在的或野生型酮还原酶的母体或参考多核苷酸经受诱变过程(如随机诱变和重组)以引入突变到所述多核苷酸中。表达并翻译所述突变的多核苷酸，从而产生对所述多肽修饰的工程酮还原酶。如本文所用，“修饰”包括氨基酸置换、缺失和插入。可将任何一种修饰或修饰的组合引入到天然存在的酶学活性多肽以产生工程酶，然后通过各种方法筛选所述工程酶以鉴定具有特异性酶性质的期望改进的多肽和对应的多核苷酸。编码具有改进性质的工程酮还原酶的多核苷酸可经受另外回合的诱变处理以产生期望的酶性质进一步改进的多肽。

如本文所用，具有“改进的酶性质”的酮还原酶是指与参考酮还原酶相比显示任何酶性质的改进的酮还原酶。对于本文所述的工程酮还原酶，通常进行与野生型酿酒酵母酮还原酶(SEQ ID NO：2)的比较，尽管在一些实施方案中，所述参考酮还原酶可以是另一个改进的工程酮还原酶。期望改进的酶性质包括但不限于酶活性、热稳定性、pH活性特性、辅因子需求、对抑制剂(例如产物抑制)的不应性(refractoriness)、立体特异性和立体选择性。

如本文工程酮还原酶的环境所用，“源自”识别起源酮还原酶、和/或工程所基于的编码这种酮还原酶的基因。例如，SEQ ID NO：80的工程酮还原酶是通过多代人工进化编码SEQ ID NO：2的酿酒酵母酮还原酶的基因而获得的。因此，这种工程酮还原酶“源自”SEQ ID NO：2的野生型酮还原酶。

尽管不希望受任何操作理论的限制，但是认为酶性质的改进来源于多肽链中的修饰引进，所述修饰引进有效扰乱所述酶的结构功能和/或其与另一个分子(例如底物)的相互作用。多肽的某些区域，例如参与催化和底物结合结构域的氨基酸可对酶活性是决定性的，以致对这些区域的小干扰可对酶功能具有重大的影响。某些氨基酸残基可处在维持酶的二级或三级结构的重要位置，因此当被修饰时，也产生酶性质的显著变化。另一方面，多肽的某些区域可具有整体结构作用或形成较少参与酶功能的关键性方面的酶部分(例如连接α螺旋的肽环)，因而仅当此区域中已积聚了很多置换时，才对酶功能产生可测量的影响。因此，在一些实施方案中，产生改进的酮还原酶性质的天然存在的多肽的修饰数目可包括1个或更多个氨基酸、2个或更多个氨基酸、5个或更多个氨基酸、10个或更多个氨基酸、或者20个或更多个氨基酸、高至参考酶序列氨基酸总数的10％、高至氨基酸总数的20％或者高至氨基酸总数的30％。

因为技术的性质，所以基因进化方法如DNA诱变和重组偏好氨基酸置换的修饰。因此，在各种实施方案中，酶性质的改进可来源于1个氨基酸残基、2个或更多个氨基酸残基、5个或更多个氨基酸残基、10个或更多个氨基酸残基、15个或更多个氨基酸残基、20个或更多个氨基酸残基、高至组成参考酶序列的氨基酸总数的10％、高至氨基酸总数的20％或者高至氨基酸总数的30％的置换。

如对熟练的技术人员来说明显的是，对大量具有改进酶性质的工程酮还原酶的氨基酸置换分析显示置换在酮还原酶多肽的某些氨基酸残基重现以及偏好某些类型的氨基酸。置换在多肽内的某些确定位置的这种重现可反映氨基酸残基对特定酶性质的影响和其被连续施加的特定的改进酶性质的选择所保留。可对置换的重现以及置换的氨基酸的类型的偏好分组来描述可允许产生改进酶性质的置换的类型。通常地，遗传编码的氨基酸根据它们的侧链性质可分成以下种类：

“亲水性氨基酸或残基”是指根据Eisenberg等人，1984，J.Mol.Biol.179：125-142的标准化的一致性疏水性标度(scale)，具有显示疏水性小于零的侧链的氨基酸或残基。遗传编码的亲水性氨基酸包括L-Thr(T)、L-Ser(S)、L-His(H)、L-Glu(E)、L-Asn(N)、L-Gln(Q)、L-Asp(D)、L-Lys(K)和L-Arg(R)。

“酸性氨基酸或残基”是指当氨基酸包含于肽或多肽中时，具有显示pK值小于约6的侧链的亲水性氨基酸或残基。在生理pH下，酸性氨基酸通常由于氢离子的丧失而具有荷负电的侧链。遗传编码的酸性氨基酸包括L-Glu(E)和L-Asp(D)。

“碱性氨基酸或残基”是指当氨基酸包含于肽或多肽中时，具有显示pK值大于约6的侧链的亲水性氨基酸或残基。在生理pH下，碱性氨基酸通常由于与水合氢离子的缔合而具有荷正电的侧链。遗传编码的碱性氨基酸包括L-His(H)、L-Arg(R)和L-Lys(K)。

“极性氨基酸或残基”是指具有在生理pH下不荷电的侧链的亲水性氨基酸或残基，但是所述侧链具有至少一个键，其中两个原子共享的电子对与原子中的一个结合得更紧密。遗传编码的极性氨基酸包括L-Asn(N)、L-Gln(Q)、L-Ser(S)和L-Thr(T)。

“疏水性氨基酸或残基”是指根据Eisenberg等人，1984，J.Mol.Biol.179：125-142的标准化的一致性疏水性标度，具有显示疏水性大于零的侧链的氨基酸或残基。遗传编码的疏水性氨基酸包括L-Pro(P)、L-Ile(I)、L-Phe(F)、L-Val(V)、L-Leu(L)、L-Trp(W)、L-Met(M)、L-Ala(A)和L-Tyr(Y)。

“芳香族氨基酸或残基”是指具有包括至少一个芳香族或杂芳香族环的侧链的亲水性或疏水性氨基酸或残基。遗传编码的芳香族氨基酸包括L-Phe(F)、L-Tyr(Y)和L-Trp(W)。尽管L-His(H)由于其杂芳香族氮原子的pKa而在上文被归类为碱性残基，但是由于其侧链包括杂芳香族环，所以其还可归类为芳香族残基。

“非极性氨基酸或残基”是指具有在生理pH下不荷电的侧链的疏水性氨基酸或残基，但是所述侧链具有由两个原子共享的电子对一般与两个原子中的每个都平等结合的键(即侧链为非极性)。遗传编码的非极性氨基酸包括L-Leu(L)、L-Val(V)、L-Ile(I)、L-Met(M)和L-Ala(A)。

“脂肪族氨基酸或残基”是指具有脂肪族烃侧链的疏水性氨基酸或残基。遗传编码的脂肪族氨基酸包括L-Ala(A)、L-Val(V)、L-Leu(L)和L-Ile(I)。

氨基酸L-Cys(C)是与众不同的，因为它可与其他L-Cys(C)氨基酸或其他含硫烷基或巯基的氨基酸形成二硫键。“半胱氨酸样残基”包括半胱氨酸和含有可用于形成二硫键的巯基部分的其他氨基酸。L-Cys(C)(和具有含-SH的侧链的其他氨基酸)以还原型自由-SH或氧化型二硫键的形式存在于肽中的能力影响L-Cys(C)是否向肽贡献净疏水性或亲水性特征。虽然根据Eisenberg(Eisenberg等人，1984，见上)的标准化的一致性标度L-Cys(C)显示0.29的疏水性，但是应理解，对于本公开内容的目的，L-Cys(C)被分类为极性亲水性氨基酸，尽管上文定义了一般分类。

氨基酸Gly(G)也是与众不同的，原因是它在其α-碳上没有侧链，因而向特定的肽序列贡献仅一个肽键。此外，由于侧链的缺乏，它是具有非手性α-碳的仅有的遗传编码的氨基酸。尽管根据Eisenberg(Eisenberg等人，1984，见上)的标准化的一致性标度Gly(G)显示0.48的疏水性，但是对于本发明的目的，Gly被分类为脂肪族氨基酸或残基。

“小氨基酸或残基”是指具有由总数为3个或更少个碳和/或杂原子(除α-碳和氢)组成的侧链的氨基酸或残基。根据上述定义，小氨基酸或残基可被进一步分类成脂肪族、非极性、极性或酸性小氨基酸或残基。遗传编码的小氨基酸包括Gly、L-Ala(A)、L-Val(V)、L-Cys(C)、L-Asn(N)、L-Ser(S)、L-Thr(T)和L-Asp(D)。

“包含羟基的氨基酸或残基”是指含羟基(-OH)部分的氨基酸。遗传编码的包含羟基的氨基酸包括L-Ser(S)、L-Thr(T)和L-Tyr(Y)。

如本领域技术人员所理解，上文定义的分类不互相排斥。实际上，小氨基酸的所述类别包括除芳香族类别之外的所有其他所述类别的氨基酸。因此，具有显示两种或更多种物理-化学性质的侧链的氨基酸可被包括在多个类别中。作为具体的实例，具有包括可电离的杂原子的杂芳香族部分的氨基酸侧链如His可显示芳香族性质和碱性性质两种性质，并且因此可被包括在芳香族类别和碱性类别两者中。任何氨基酸或残基的合适分类对本领域技术人员来说是明显的，尤其根据本文所提供的详细公开内容。

在一些实施方案中，工程酮还原酶中的置换可以是保守性置换。术语“保守性氨基酸置换”是指具有相似侧链的残基的可互换性，因此通常包括用位于相同或相似定义类别内的氨基酸置换多肽中的氨基酸。例如但不限于，具有脂肪族侧链的氨基酸可被另一种脂肪族氨基酸如丙氨酸、缬氨酸、亮氨酸、异亮氨酸和蛋氨酸置换；具有羟基侧链的氨基酸被另一种具有羟基侧链的氨基酸如丝氨酸和苏氨酸置换；具有芳香族侧链的氨基酸被另一种具有芳香族侧链的氨基酸如苯丙氨酸、酪氨酸、色氨酸和组氨酸置换；具有碱性侧链的氨基酸被另一种具有碱性侧链的氨基酸如赖氨酸、精氨酸和组氨酸置换；具有酸性例链的氨基酸被另一种具有酸性侧链的氨基酸如门冬氨酸和谷氨酸置换；以及疏水性或亲水性氨基酸分别被另一种疏水性或亲水性氨基酸置换。

在一些实施方案中，工程酮还原酶中的置换可以是保守性置换。术语“保守性氨基酸置换”是指具有相似侧链的残基的可互换性，因此通常包括用位于相同或相似氨基酸定义类别内的氨基酸置换多肽中的氨基酸。例如但不限于，具有脂肪族侧链的氨基酸可被另一种脂肪族氨基酸如丙氨酸、缬氨酸、亮氨酸、异亮氨酸和蛋氨酸置换；具有羟基侧链的氨基酸被另一种具有羟基侧链的氨基酸如丝氨酸和苏氨酸置换；具有芳香族侧链的氨基酸被另一种具有芳香族侧链的氨基酸如苯丙氨酸、酪氨酸、色氨酸和组氨酸置换；具有碱性侧链的氨基酸被另一种具有碱性侧链的氨基酸如赖氨酸、精氨酸和组氨酸置换；具有酸性侧链的氨基酸被另一种具有酸性侧链的氨基酸如门冬氨酸或谷氨酸置换；以及疏水性或亲水性氨基酸分别被另一种疏水性或亲水性氨基酸置换。

在各种实施方案中，用于产生改进的酮还原酶的置换可包括保守性置换、非保守性置换以及保守性和非保守性置换的组合。

在一些实施方案中，改进的工程酮还原酶包括天然存在的酮还原酶多肽的缺失以及其他改进的酮还原酶多肽的缺失。术语“缺失”是指通过从参考多肽中消除一个或多个氨基酸的多肽修饰。缺失可包括消除1个或多个氨基酸、2个或更多个氨基酸、5个或更多个氨基酸、10个或更多个氨基酸、15个或更多个氨基酸、或者20个或更多个氨基酸、高至组成参考酶的氨基酸总数的10％、或者高至氨基酸总数的20％，同时保留酶活性和/或保留工程酮还原酶的改进性质。缺失可涉及多肽的内在部分和/或末端部分。在各种实施方案中，缺失可包括连续的区段或可以是不连续的。

在其他的实施方案中，改进的工程酮还原酶包括一个或多个氨基酸向天然存在的酮还原酶多肽的插入以及一个或多个氨基酸向其他改进的酮还原酶多肽的插入。插入可在多肽的内在部分或者羧基端或氨基端。本文所用的插入包括本领域已知的融合蛋白。所述插入可以是氨基酸的连续区段或被天然存在的多肽中的一个或多个氨基酸分开。

如上文所述，引入到天然存在的多肽以产生工程酮还原酶的各种修饰可针对所述酶的特异性质。因此，在一些实施方案中，所述工程酮还原酶多肽的改进性质是增加的酶活性，通常表现为与参考酮还原酶(即天然存在的酮还原酶)相比比活性(例如生成的产物/时间/蛋白重量)的增加。测定酶活性的示例性方法在实施例中提供。涉及酶活性的任何性质均可被影响，所述性质包括经典酶性质K_m、V_max或k_cat，它们的变化可导致酶活性的增加。酶活性的改进可从对应的野生型酮还原酶的酶活性的约1.5倍到比SEQ ID NO：2的天然存在的酮还原酶的酶活性多至2倍、5倍、10倍、20倍、25倍、50倍、75倍、100倍、150倍、200倍、250倍、300倍或更多倍。在特定的实施方案中，所述工程酮还原酶显示比野生型酮还原酶的酶活性大1.5至50倍、1.5至100倍、1.5至150倍、1.5至200倍、1.5至250倍、或1.5至300倍范围内的改进的酶活性。熟练的技术人员应理解，任何酶的活性都受扩散限制以使催化转换速率(turnover rate)不超过底物(包括任何需要的辅因子)的扩散速率。扩散限值的理论最大值或k_cat/K_m一般为约10⁸至10⁹(M^-1 s^-1)。因此，酮还原酶的酶活性的任何改进具有与酮还原酶所作用的底物的扩散速率有关的上限。酮还原酶活性可通过用于测量酮还原酶的标准测定中的任何一种(如NADPH的吸光度或荧光由于其伴随酮还原成对应的醇的氧化作用而减少)或通过在偶联测定中生成的产物来测量。如本文进一步详细描述，酶活性的比较是在设定条件下使用酶的确定制品和确定的测定进行的。一般来说，当比较溶解产物时，确定细胞数和所测蛋白的量，并使用相同的表达系统和相同的宿主细胞以使由宿主细胞生成和存在于溶解产物中的酶的量的差异降至最小。

在一些实施方案中，具有改进的酶活性的工程酮还原酶包括源于SEQID NO：2的酿酒酵母酮还原酶的工程多肽。在一些实施方案中，所述工程酮还原酶包括与SEQ ID NO：2具有至少约90、91、92、93、94、95、96、97、98或99％同一性的氨基酸序列。可被修饰以产生具有改进酶活性的工程多肽的氨基酸残基在图4中示出，其中Xⁿ表示修饰的氨基酸残基。在一些实施方案中，SEQ ID NO：2的一个或多个天然存在的氨基酸(amino)残基可进行如下置换：

X⁶是极性或酸性氨基酸残基；

X²⁷是脂肪族或碱性氨基酸残基；

X³¹是包含羟基的或脂肪族氨基酸残基；

X³⁶是小氨基酸残基；

X⁴⁸是碱性氨基酸残基；

X⁶³是疏水性或芳香族氨基酸；

X⁶⁵是包含羟基的或小氨基酸残基；

X⁸⁶是脂肪族或疏水性氨基酸残基；

X¹²⁵是脂肪族或芳香族氨基酸残基；

X¹⁵²是碱性氨基酸残基；

X¹⁶⁰是包含羟基的或小氨基酸残基；

X¹⁶⁵是极性或酸性氨基酸残基；

X¹⁹⁴是芳香族氨基酸或极性亲水性氨基酸残基；

X²¹⁴是极性亲水性氨基酸残基；

X²¹⁸是包含羟基的氨基酸残基；

X²³⁴是极性亲水性氨基酸残基；

X²⁴⁸是脂肪族氨基酸残基；

X²⁵⁰是碱性氨基酸残基；

X²⁶³是酸性或极性氨基酸残基；

X²⁹⁰是酸性氨基酸残基；

X²⁹⁶是脂肪族氨基酸残基；

X²⁹⁷是芳香族氨基酸残基；

X³⁰¹是脂肪族、包含羟基的、酸性、亲水性或碱性氨基酸残基；和/或

X³⁰⁷是芳香族、极性或包含羟基的氨基酸残基。在一些实施方案中，所述酮还原酶具有所有这些残基特征。

在一些实施方案中，所述酮还原酶具有这些残基特征中的一种或多种。在一些实施方案中，这些残基位置中的至少一种不包括是关于SEQ IDNO：2的保守性突变的置换。在一些实施方案中，X⁶³是芳香族残基。在一些实施方案中，X⁶³是色氨酸。在一些实施方案中，在其他位置的残基可以是关于SEQ ID NO：2的保守性突变。

在一些实施方案中，SEQ ID NO：2的酮还原酶的氨基酸残基可用一种或多种如下的特定氨基酸置换：

X⁶是E；

X²⁷是A或K；

X³¹是S或P；

X³⁶是V；

X⁴⁸是H；

X⁶³是W；

X⁶⁵是G或S；

X⁸⁶是I；

X¹²⁵是L；

X¹⁵²是R；

X¹⁶⁰是T或S；

X¹⁶⁵是E；

X¹⁹⁴是C；

X²¹⁴是R或H；

X²¹⁸是T；

X²³⁴是Q；

X²⁴⁸是I；

X²⁵⁰是R；

X²⁶³是E；

X²⁹⁰是V或D；

X²⁹⁶是I；

X²⁹⁷是F或W；

X³⁰¹是R、K、A、V、S、T、Y、D、E、P或Q；和/或

X³⁰⁷是H、N或S。

在一些实施方案中，具有改进酶活性的工程酮还原酶具有上文所指出的氨基酸残基的子集的置换。因此，在一些实施方案中，所述氨基酸置换可发生于以下氨基酸位置中的一种或多种：X²⁷、X³¹、X³⁶、X⁴⁸、X⁶³、X⁶⁵、X⁸⁶、X¹²⁵、X¹⁵²、X¹⁶⁰、X¹⁹⁴、X²¹⁸、X²⁴⁸、X²⁵⁰、X²⁹⁰、X²⁹⁶、X²⁹⁷、X³⁰¹和X³⁰⁷，其中用于置换的氨基酸残基按上文所述进行选择。

在一些实施方案中，所述工程酮还原酶包括选自以下的一种或多种突变：R27A、R27K、N31S、A36V、Y48H、I63W、R65G、R65S、L86I、F125L、K152R、A160T、Y194C、A218T、V248I、K250R、E290D、L296V、Y297W、Y297F、L301K、L301R、L301A、L301S、L301E、L301P、L301Q、L301V、L301T、L301Y、L301D、Y307H、Y307N和Y307S。

本文还显示，发现其置换使得酮还原酶具有改进性质的各种氨基酸残基位置在所述酮还原酶的某些区段群集(cluster)，这允许所述区段的靶向修饰。因此，在一些实施方案中，酮还原酶多肽的选定区段可进行修饰。对于SEQ ID NO：2参考序列，影响酮还原酶酶活性的区段包括氨基酸残基27至36、40至65、103至125、144至169、233至265和/或287至312所表示的那些区段以及其他区段。可修饰在每个区段或区段的组合内的一个或多个氨基酸残基。在一些实施方案中，用于置换的对应氨基酸序列和位置包括：

X²⁷WYKX³¹EETDX³⁶

X⁴⁰SLX⁴³X⁴⁴QX⁴⁶VX⁴⁸ALX⁵¹LPGX⁵⁵X⁵⁶HX⁵⁸DX⁶⁰AX⁶²X⁶³YX⁶⁵

X¹⁰³LDX¹⁰⁶ALKK MGTX¹¹⁴YVDLYLX¹²¹HSPX¹²⁵

X¹⁴⁴LYKX¹⁴⁸GKAX¹⁵²NIGVSX¹⁵⁸F X¹⁶⁰VEDLX¹⁶⁵RILX¹⁶⁹

X²³³X²³⁴KYX²³⁷KX²³⁹EAQIILRWX²⁴⁸TX²⁵⁰RGX²⁵³LPVTTSSKPX²⁶³RX²⁶⁵；和

X²⁹⁰HEPLRX²⁹⁶X²⁹⁷WNKX³⁰¹YGKYNX³⁰⁷AAX³¹⁰X³¹¹X³¹²

其中Xⁿ指示氨基酸置换的位置。

在一些实施方案中，具有改进酶活性的工程酮还原酶具有选自表1所列举的氨基酸序列的氨基酸序列：

^*＝150-500％SEQ ID NO：2的酶活性

^**＝500-900％SEQ IDNO：2的酶活性

^***＝900-1600％SEQ ID NO：2的酶活性

^****＝大于1600％SEQ ID NO：2的酶活性

+＝变体在所指出的温度下热处理16小时后保留残基活性

ND＝未测定

在其他的实施方案中，所述工程酮还原酶包括与工程酶所源自的天然存在的酮还原酶相比具有改进的热稳定性的酮还原酶。热稳定酶如在用于大规模生产的高底物浓度的条件下允许与底物进行更长时间的温育，并且还使所需酶的量降至最低。具有“改进的热稳定性”的酶是指当在规定的测定条件下暴露于设定温度或一组温度时，展示了与参考酶的失活抗性相比增加的失活抗性的酶。

许多方法可用于测量酶热稳定性。酶可在一组标准的测定条件(例如离子强度、pH、蛋白浓度等)下于各种温度处理达规定的时段。半失活温度(即在热处理达规定的时间后50％失活发生的温度)用于比较酶的热稳定性。测定热稳定性的另一种方法是在设定温度下处理酶并且测量剩余的酶活性量。将剩余的酶活性量与在相似或相同条件下制备的天然存在的酶的剩余活性进行比较。用于分析热稳定性的有用温度包括用于进行反应(如在大规模反应中)的反应温度和/或用于选择工程酶的改进的热稳定性的温度。例如，所述工程酶可在约30℃或以上、约35℃或以上、40℃或以上、45℃或以上、50℃或以上、55℃或以上、至约65℃的温度下具有与参考酶(例如天然存在的酶)相比改进的热稳定性。在一些实施方案中，所述酶可具有改进的热稳定性，其中所述工程酶与参考酶相比保留约10％或更多的活性、约15％或更多的活性、约20％或更多的活性、约30％或更多的活性、约50％或更多的活性、约70％或更多的活性、约90％或更多的活性。在处理条件下，酶活性显示热稳定性增强的时间可包括约5小时或更多、约6小时或更多、约12小时或更多、约18小时或更多、约24小时或更多、约36小时或更多、约48小时或更多、约72小时或更多。底物在热处理期间可存在或不存在，尽管已知在某些情况下底物的存在稳定酶结构。

在其他的实施方案中，酶的热稳定性可通过测定蛋白折叠稳定性，如通过用量热术或圆二色性法(circular dichorism)检测蛋白解折叠来测量。例如，为了测定工程酮还原酶和天然存在的酮还原酶的热稳定性，可使用CD特征在不同温度下的变化。酶的解折叠速率常数的阿累尼乌斯(Arrhenius)曲线图通过使用温度跃迁(例如从酶有活性的温度到酶无活性的温度)和测量蛋白结构的变化来产生。可比较失活温度下解折叠反应的一级速率常数、活化焓以及稳态和过渡态之间的活化自由能。通常地，活化自由能随着酶热稳定性的增加而增加。用于测定热稳定性的其他方法对熟练的技术人员来说是明显的。

在一些实施方案中，所述改进的热稳定性可与酮还原酶的其他性质分开，而在其他的实施方案中，所述热稳定性是与另一种改进的性质一起观察到的。在一些实施方案中，包括具有改进的热稳定性的工程酮还原酶的酮还原酶源于SEQ ID NO：2的酿酒酵母酮还原酶。在一些实施方案中，具有改进的热稳定性的工程酮还原酶在pH 7.0于37至50℃的温度范围下处理16小时后，保留约20％或更多的酶活性。相比之下，SEQ ID NO：2的天然存在的酮还原酶在pH 7.0于37℃的温度下温育16小时后，仅保留5-10％的其活性，而当在相同的条件于更高的温度下温育时，则基本上没有保留活性。

在一些实施方案中，具有改进热稳定性的工程酮还原酶包括与SEQ IDNO：2对应的氨基酸序列并且包括下述置换的一种或多种：

X⁶是极性或酸性氨基酸残基；

X³¹是包含羟基的或脂肪族氨基酸残基；

X⁴⁴是酸性氨基酸残基；

X⁴⁶是脂肪族氨基酸残基；

X⁵⁵是脂肪族氨基酸残基；

X⁵⁶是脂肪族氨基酸；

X⁶⁰是包含羟基的或小氨基酸；

X⁶³是疏水性或芳香族氨基酸；

X⁷⁶是氨基酸残基M；

X¹⁰³是包含羟基的氨基酸残基；

X¹⁰⁶是脂肪族氨基酸残基；

X¹¹⁴是小氨基酸残基；

X¹²¹是疏水性或脂肪族氨基酸残基；

X¹⁴⁴是亲水性或碱性氨基酸残基；

X¹⁴⁸是包含羟基的氨基酸残基；

X¹⁵⁸是芳香族氨基酸残基；

X¹⁶⁰是包含羟基的或小氨基酸残基；

X¹⁶⁵是极性或酸性氨基酸残基；

X¹⁶⁹是脂肪族或碱性氨基酸残基；

X¹⁸⁵是芳香族或脂肪族氨基酸残基；

X¹⁹⁴是芳香族氨基酸或极性亲水性氨基酸残基；

X¹⁹⁹是极性氨基酸残基；

X²¹⁴是芳香族或碱性氨基酸残基；

X²²³是芳香族氨基酸残基；

X²³⁴是极性亲水性氨基酸残基；

X²³⁷是亲水性或小氨基酸残基；

X²³⁹是包含羟基的氨基酸残基；

X²⁵³是脂肪族氨基酸残基；和/或

X²⁶³是酸性或极性氨基酸残基。

在一些实施方案中，X⁶³是芳香族残基。在一些实施方案中，X⁶³是色氨酸。在一些实施方案中，所述酮还原酶在除上文所列出的那些位置之外的其他位置包括一种或多种保守性突变。

X⁶是E；

X³¹是P；

X⁴⁴是D；

X⁴⁶是L；

X⁵⁵是V；

X⁵⁶是V；

X⁶⁰是T；

X⁶³是V；

X⁷⁶是M；

X¹⁰³是S；

X¹⁰⁶是I；

X¹¹⁴是G；

X¹²¹是I或M；

X¹⁴⁴是R；

X¹⁴⁸是T；

X¹⁵⁸是H；

X¹⁶⁰是S；

X¹⁶⁵是E；

X²¹⁴是R或H；

X²²³是H、R或G；

X²³⁴是Q；

X²³⁷是N、G、R或Q；

X²³⁹是T；和/或

X²⁵³是A。

在一些实施方案中，具有改进热稳定性的工程酮还原酶具有上文所指出的氨基酸残基的子集的置换。因此，在一些实施方案中，所述氨基酸置换可发生于以下氨基酸位置中的一种或多种：X⁴⁴、X⁴⁶、X⁵⁵、X⁵⁶、X⁶⁰、X⁶³、X⁷⁶、X¹⁰³、X¹⁰⁶、X¹¹⁴、X¹²¹、X¹⁴⁴、X¹⁴⁸、X¹⁵⁸、X²²³、X²³⁷、X²³⁹和X²⁵³，其中用于置换的氨基酸残基按上文所述进行选择。

在一些实施方案中，具有改进热稳定性的工程酮还原酶与SEQ ID NO：2相比包括下述突变的一种或多种：E44D、I46L、I55V、I56V、A60T、I63V、L76M、G103S、L106I、D114G、L121I、Q144R、S148T、N158H、Q223H、I237G、I237N、I237R、S239T和V253A。

如对具有改进酶活性的工程酮还原酶观察到的，也发现其置换使得工程酮还原酶具有改进的热稳定性的各种氨基酸残基位置在SEQ ID NO：2的酮还原酶的某些区段群集，这允许靶向修饰。导致热稳定性改进的置换与发生在具有改进酶活性的工程酶中的那些置换重叠，尽管有些不重叠。因此，在一些实施方案中，酮还原酶多肽的选定区段可进行修饰以产生具有改进热稳定性的工程酮还原酶。对于SEQ ID NO：2参考序列，影响酮还原酶酶活性的区段包括氨基酸残基27至36、40至65、103至125、144至169、233至265和287至312所表示的那些区段以及其他区段。在一些实施方案中，影响酮还原酶酶活性的区段包括氨基酸残基27-32、60-65、90-93、120-125、157-159、208-211和293-306所表示的那些区段以及其他区段。可修饰在每个区段或区段的组合内的一个或多个氨基酸残基。

在一些实施方案中，用于置换的对应氨基酸序列和位置包括：

X²⁷WYKX³¹EETDX³⁶

X¹⁰³LDX¹⁰⁶ALKK MGTX¹¹⁴YVDLYLX¹²¹HSPX¹²⁵

其中Xⁿ指示氨基酸置换的位置。保守性置换和非保守性置换两者都可在如所指出的区段中进行。

在一些实施方案中，改进的性质可以是性质的组合，例如改进的酶活性和改进的热稳定性。在一些实施方案中，所述工程酮还原酶包括具有改进的酶活性和改进的酶稳定性的组合、具有与SEQ ID NO：2的酮还原酶的野生型序列对应的氨基酸序列并且包括选自以下的一种或多种突变的酮还原酶：Q6E、N31P、A160S、Q165E、Q214H、Q214R、E234Q、Q263E。

在一些实施方案中，所述工程酮还原酶包括具有改进的酶活性和/或稳定性的组合、具有与SEQ ID NO：2的酮还原酶的野生型序列对应的氨基酸序列并且包括选自以下的一种或多种突变的酮还原酶：N40Y、V43L、K51E、I58V、E62Q、A73P、K79R、K152Q、K169E、F185I、Q189H、G192D、H200L、D201G、K215E、K215M、K216R、D221V、S233C、I237D、K250E、I265V、L287R、K304R、Q310R、K311E、V312S、V312E。

应理解，所述工程酮还原酶并不限于通过诱变或其他基因进化技术直接鉴定的那些，而且还包括改进的工程酮还原酶多肽的变体或类似物。本文所用的术语“变体”或“类似物”是指由具有酮还原酶活性并保留或未保留所述改进的性质的区段组成并且与工程酮还原酶的部分具有大致同一性的多肽。在一些实施方案中，类似物多肽包括关于工程序列的一种或多种氨基酸残基的保守性氨基酸置换或添加或缺失。类似物通常为至少酶学活性的片段并且通常和SEQ ID NO：2的全长天然存在的参考多肽一样长(例如312个氨基酸残基)。

在一些实施方案中，所述工程酮还原酶多肽的变体或类似物可包括与参考工程酮还原酶或工程酮还原酶的酶学活性的片段具有约70％或更多的氨基酸同一性、约80％或更多的氨基酸同一性、约90％或更多的氨基酸同一性、约95％或更多的氨基酸同一性、约97％或更多的氨基酸同一性、约98％或更多的氨基酸同一性、或者约99％或更多的氨基酸同一性的酶学活性的酮还原酶多肽。

在一些实施方案中，所述参考工程酮还原酶选自表1中所列举的氨基酸序列。改进的酮还原酶的示例性参考序列是SEQ ID NO：314。在一些实施方案中，所述工程酮还原酶多肽的变体或类似物可包括与SEQ ID NO：314或SEQ ID NO：314的酶学活性的片段具有约95.5％或更多氨基酸同一性、约97％或更多氨基酸同一性、约98％或更多氨基酸同一性、或者约99％或更多氨基酸同一性的酶学活性的酮还原酶多肽。

改进的酮还原酶的另一个示例性参考序列是SEQ ID NO：316。在一些实施方案中，所述工程酮还原酶多肽的变体或类似物可包括与SEQ ID NO：316或SEQ ID NO：316的酶学活性的片段具有约95.5％或更多氨基酸同一性、约97％或更多氨基酸同一性、约98％或更多氨基酸同一性、或者约99％或更多氨基酸同一性的酶学活性的酮还原酶多肽。

改进的酮还原酶的另一个示例性参考序列是SEQ ID NO：318。在一些实施方案中，所述工程酮还原酶多肽的变体或类似物可包括与SEQ ID NO：318或SEQ ID NO：318的酶学活性的片段具有约95.5％或更多氨基酸同一性、约97％或更多氨基酸同一性、约98％或更多氨基酸同一性、或者约99％或更多氨基酸同一性的酶学活性的酮还原酶多肽。

改进的酮还原酶的另一个示例性参考序列是SEQ ID NO：376。在一些实施方案中，所述工程酮还原酶多肽的变体或类似物可包括与SEQ ID NO：376或SEQ ID NO：376的酶学活性的片段具有约95.5％或更多氨基酸同一性、约97％或更多氨基酸同一性、约98％或更多氨基酸同一性、或者约99％或更多氨基酸同一性的酶学活性的酮还原酶多肽。

在一些实施方案中，所述改进的酮还原酶多肽区段可被缺失以产生多肽片段。本文所用的术语“片段”是指具有氨基末端和/或羧基末端缺失，但是其中剩余的氨基酸序列与序列中的对应位置具有同一性的多肽。片段可以是至少14个氨基酸长、至少20个氨基酸长、至少50个氨基酸长或更长，且可多达SEQ ID NO：2的全长天然存在酮还原酶多肽的70％、80％、90％、95％、98％和99％。

改进的酮还原酶可存在于细胞内，存在于细胞基质中或以各种形式如溶解产物或分离的制品来制备。因此，在一些实施方案中，所述改进的酮还原酶可以是分离的多肽。术语“分离的多肽”是指与天然伴随它的其他污染物(例如蛋白、脂质和多核苷酸)大致分离的多肽。所述术语包括已从其天然存在的环境或表达系统(例如宿主细胞或体外合成)中取出(remove)或纯化的多肽。

在一些实施方案中，所述分离的改进酮还原酶多肽是大致纯的多肽组合物。术语“大致纯的多肽”是指其中多肽种类是存在的主要种类(即在摩尔或重量基础上它比组合物中的其他任何单独的大分子种类更多)的组合物，并且当目标种类包括至少约50％的存在的大分子种类摩尔或％重量时，其通常是大致纯化的组合物。一般来说，大致纯的酮还原酶组合物将包括约60％或更多、约70％或更多、约80％或更多、约90％或更多、约95％或更多、以及约98％或更多的存在于组合物中的所有大分子种类摩尔或％重量。在一些实施方案中，目标种类被纯化至基本均一性(homogeneity)(即通过常规检测法在组合物中不能检测出污染物种类)，其中所述组合物大致由单一大分子种类组成。溶剂种类、小分子(＜500道尔顿)和元素离子种类不被视为大分子种类。

6.3编码工程酮还原酶的多核苷酸

在另一个方面中，本公开内容提供了编码工程酮还原酶的多核苷酸。所述多核苷酸可与一种或多种控制基因表达的异源调节序列可操作地连接，以产生能表达多肽的重组多核苷酸。包含编码工程酮还原酶的异源多核苷酸的表达构建体可被引入到适合的宿主细胞以表达对应的酮还原酶多肽。术语“异源”多核苷酸是指通过实验室技术引入到宿主细胞的任何多核苷酸，并且包括从宿主细胞中移除、进行实验室操作然后再引入到宿主细胞的多核苷酸。

由于对与各种氨基酸对应的密码子的认识，因此蛋白序列的可用性提供了能编码主题(subject)的所有多核苷酸的描述。遗传密码的简并性(即相同的氨基酸被替代密码子或同义密码子编码)允许制备非常多的核酸，所有这些核酸均编码本文所公开的改进酮还原酶。因此，鉴定了特定的氨基酸序列后，本领域技术人员能够通过以不改变蛋白质的氨基酸序列的方法简单地修饰所述序列的一个或多个密码子而制备任何数目的不同核酸。在这点上，本公开内容明确预期了可通过选择基于可能的密码子选择的组合而制备的每种和每个可能的多核苷酸变体，并且对于本文所公开的任何多肽(包括表1中所提供的氨基酸序列)，所有这些变体均应视为明确公开。

在一些实施方案中，编码酮还原酶的多核苷酸可进行密码子优化以实现从选择用于表达的宿主生物体的最佳制备。术语“密码子优化”是指编码蛋白多核苷酸的密码子变化为特定生物体中优先使用的那些密码子以使所编码的蛋白在感兴趣的生物体中有效地表达。尽管遗传密码具有简并性，大多数氨基酸由几个密码子(称为“同义(synonym)”密码子或“同义的(synonymous)”密码子)表示，但是众所周知，特定生物体的密码子使用是非随机的并且偏好特定的密码子三联体。关于给定的基因、具有共同功能或祖先起源的基因、与低拷贝数蛋白比较的高表达蛋白和生物体基因组的聚集蛋白编码区，这种密码子使用偏好性(codon usage bias)可以更高。

术语“优选”、“最佳”或“高密码子使用偏好性”密码子可互换地指在蛋白编码区中以比编码相同氨基酸的其他密码子更高的频率使用的密码子。优选密码子的确定可与单个基因、具有共同功能或起源的一组基因、高表达基因的密码子使用，整个生物体的聚集蛋白编码区中的密码子频率、相关生物体的聚集蛋白编码区的密码子频率，或其组合有关。频率随基因表达水平增加的密码子通常是用于表达的最佳密码子。

已知多种方法用于测定特定生物体中的密码子频率(例如密码子使用、相对同义密码子使用)和密码子喜好，所述方法包括多变量分析(multivariatanalysis)如使用聚类分析或对应分析、以及基因中使用的密码子的有效数量(参见GCG Codon Preference，Genetics Computer Group WisconsinPackage；CodonW，John Peden，University of Nottingham；McInerney，J.O，1998，Bioinformatics 14：372-73；Stenico等人，1994，Nucleic Acids Res.222437-46；Wright，F.，1990，Gene 87：23-29)。

具有可用的密码子使用表的生物体的列表在不断增加(参见例如，Wada等人，1992，Nucleic Acids Res.20：2111-2118；Nakamura等人，2000，Nucl.Acids Res.28：292；Duret等人，见上；Henaut和Danchin，“Escherichiacoli and Salmonella(大肠杆菌和沙门氏菌)”1996，Neidhardt等人编，ASMPress，Washington D.C.，第2047-2066页)。用于获得密码子使用的数据源可依赖于任何可用的能编码蛋白的核苷酸序列。这些数据集包括实际上已知编码表达蛋白的核酸序列(例如完全蛋白编码序列-CDS)、表达序列标签(ESTS)或基因组序列的预测编码区(参见例如Mount，D.，Bioinformatics：Sequence and Genome Analysis(生物信息学：序列和基因组分析)，第8章，Cold Spring Harbor Laboratory Press，Cold Spring Harbor，N.Y.，2001；Uberbacher，E.C，1996，Methods Enzymol.266：259-281；Tiwari等人，1997，Comput.Appl.Biosci.13：263-270)。

在各种实施方案中，优选选择适合在其中制备蛋白质的宿主细胞的密码子。例如，细菌中使用的优选密码子用于在细菌中表达基因；酵母中使用的优选密码子用于酵母中的表达；并且哺乳动物中使用的优选密码子用于哺乳动物细胞中的表达。例如，SEQ ID NO：1的多核苷酸已进行密码子优化以用于大肠杆菌中的表达，但是在其他的方面其编码酿酒酵母的天然存在的酮还原酶。

在某些实施方案中，因为天然序列将包括优选的密码子并且因为不是所有氨基酸残基都需要使用优选密码子，所以不需要替换所有密码子以优化酮还原酶的密码子使用。因此，密码子优化的编码酮还原酶的多核苷酸可在约40％、50％、60％、70％、80％或大于90％的全长编码区的密码子位置包含优选的密码子。

在所述实施方案中，编码工程酮还原酶的多核苷酸源于酿酒酵母ydl基因。在一些实施方案中，编码工程酮还原酶的多核苷酸选自SEQ ID NO：15、17、19、21、23、25、27、29、31、33、35、37、39、41、43、45、47、49、51、53、55、57、59、61、63、65、67、69、71、73、75、77、79、81、83、85、87、89、91、93、95、97、99、101、103、105、107、109、111、113、115、117、119、121、123、125、127、129、131、133、135、137、139、141、143、145、147、149、151、153、155、157、159、161、163、165、167、169、171、173、175、177、179、181、183、185、187、189、191、193、195、197、199、201、203、205、207、209、211、213、215、217、219、221、223、225、227、229、231、233、235、237、239、241、243、245、247、249、251、253、255、257、259、261、263、265、267、269、271、273、275、277、279、281、283、285、287、289、291、293、295、297、299、301、303、305、307、309、311、313、315、317、319、321、323、325、327、329、331、333、335、337、339、341、343、345、347、349、351、353、355、357、359、361、363和365。

这些多核苷酸编码由表1中列出的氨基酸序列表示的对应多肽，所述对应多肽是通过使大肠杆菌密码子优化的酵母ydl基因经受本文所述的定向基因进化技术而衍生的。

在其他的实施方案中，所述多核苷酸包括与编码具有改进酶性质的工程酮还原酶或具有改进性质的工程酮还原酶的片段的参考多核苷酸在核苷酸水平具有约80％或更多序列同一性、约85％或更多序列同一性、约90％或更多序列同一性、约95％或更多序列同一性、约98％或更多序列同一性或者99％或更多序列同一性的多核苷酸。在一些实施方案中，所述参考多核苷酸选自由以下表示的多核苷酸序列：SED ID NO：15、17、19、21、23、25、27、29、31、33、35、37、39、41、43、45、47、49、51、53、55、57、59、61、63、65、67、69、71、73、75、77、79、81、83、85、87、89、91、93、95、97、99、101、103、105、107、109、111、113、115、117、119、121、123、125、127、129、131、133、135、137、139、141、143、145、147、149、151、153、155、157、159、161、163、165、167、169、171、173、175、177、179、181、183、185、187、189、191、193、195、197、199、201、203、205、207、209、211、213、215、217、219、221、223、225、227、229、231、233、235、237、239、241、243、245、247、249、251、253、255、257、259、261、263、265、267、269、271、273、275、277、279、281、283、285、287、289、291、293、295、297、299、301、303、305、307、309、311、313、315、317、319、321、323、325、327、329、331、333、335、337、339、341、343、345、347、349、351、353、355、357、359、361、363和365。

在一些实施方案中，所述多核苷酸编码酶学活性的酮还原酶并且在规定条件如中等严格或高严格条件下与编码本公开内容的工程酮还原酶的序列的互补序列杂交。短语“严格杂交”在本文用于指核酸杂交体(hybrid)具有稳定性的条件。如本领域技术人员已知，杂交体的稳定性用杂交体的解链温度(T_m)反映。一般而言，杂交体的稳定性是离子强度、温度、G/C含量和离液剂存在的函数。多核苷酸的T_m值可使用用于预测解链温度的已知方法来计算(参见例如Baldino等人，Methods Enzymology 168：761-777；Bolton等人，1962，Proc.Natl.Acad.Sci.USA 48：1390；Bresslauer等人，1986，Proc.Natl.Acad.Sci USA 83：8893-8897；Freier等人，1986，Proc.Natl.Acad.Sci USA 83：9373-9377；Kierzek等人，Biochemistry 25：7840-7846；Rychlik等人，1990，Nucleic Acids Res 18：6409-6412(勘误，1991，NucleicAcids Res 19：698)；Sambrook等人，见上)；Suggs等人，1981，DevelopmentalBiology Using Purified Genes(使用纯化的基因的发育生物学)(Brown等人编)，第683-693页，Academic Press；和Wetmur，1991，Crit Rev BiochemMol Biol 26：227-259。所有出版物通过引用并入本文)。

一般来说，杂交反应在较低严格性的条件下进行，随后不同但更高的严格性的洗涤。通常地，提及的“杂交严格性”与此类洗涤条件有关。术语“中等严格杂交”是指允许靶-DNA结合与靶DNA具有约60％同一性、优选约75％同一性、约85％同一性；与靶-多核苷酸具有大于约90％同一性的互补的核酸的条件。示例性的中等严格条件是等同于在42℃于50％甲酰胺、5×Denhart溶液、5×SSPE、0.2％SDS中杂交、之后在42℃于0.2×SSPE、0.2％SDS中洗涤的条件。

对于确定多核苷酸序列，术语“高严格性杂交”通常是指比在溶液(solution)条件下测定的热解链温度T_m低约10℃或更少的条件。在一些实施方案中，高严格性条件是指仅允许在65℃于0.018M NaCl中形成稳定杂交体的那些核酸序列的杂交的条件(即，如果杂交体在65℃下于0.018MNaCl中不稳定，那么它在高严格性条件下也将不稳定，如本文所预期)。例如，高严格性条件可通过在等同于42℃下50％甲酰胺、5×Denhart溶液、5×SSPE、0.2％SDS的条件下杂交、之后在65℃于0.1×SSPE和0.1％SDS中洗涤来提供。其他高严格性杂交条件以及中等严格条件在上文引用的参考文献中描述。

编码改进酮还原酶多肽的分离的多核苷酸可以多种方法操作以提供所述多肽的表达。根据表达载体，可需要或必须在将所述分离的多核苷酸插入到载体之前对其进行操作。利用重组DNA方法修饰多核苷酸和核酸序列的技术在本领域中是众所周知的。指导在以下中提供：Sambrook等人，2001，Molecular Cloning：A Laboratory Manual(分子克隆实验手册)，第3版，Cold Spring Harbor Laboratory Press；和Current Protocols in MolecularBiology(分子生物学最新方案)，Ausubel.F.编，Greene Pub.Associates，1998，2006更新版。

术语“控制序列”在本文定义为包括对本公开内容多肽的表达必要的或有利的所有组件(component)。每种控制序列对于编码所述多肽的核酸序列可以是天然的或外源的。这些控制序列包括但不限于前导区、多聚腺苷化序列、前肽序列、启动子、信号肽序列和转录终止子。在最低限度下，所述控制序列包括启动子以及转录和翻译停止信号。所述控制序列可与连接体(linker)一起提供，这是为了引入特定的限制位点以促进控制序列与编码多肽的核酸序列的编码区的连接。

术语“可操作地连接”在本文定义为其中控制序列适当地置于相对于DNA序列的编码序列的位置以使所述控制序列指导多核苷酸和/或多肽的表达的结构(configuration)。

所述控制序列可以是适当的启动子序列。“启动子序列”是由宿主细胞识别的用于表达编码区的核酸序列。启动子序列包含转录控制序列，所述转录控制序列介导多肽的表达。启动子可以是在选择的宿主细胞中显示转录活性的任何核酸序列(包括突变体、截短的和杂合启动子)，并且可从编码与宿主细胞同源或者异源的细胞外或细胞内多肽的基因得到。

对于细菌宿主细胞，用于指导本公开内容的核酸构建体的转录的合适启动子包括从以下获得的启动子：大肠杆菌乳糖操纵子、天蓝色链霉菌(Streptomyces coelicolor)琼脂糖酶基因(dagA)、枯草芽孢杆菌(Bacillussubtilis)果聚糖蔗糖酶基因(sacB)、地衣芽孢杆菌(Bacillus licheniformis)α-淀粉酶基因(amyL)、嗜热脂肪芽孢杆菌(Bacillus stearothermophilus)麦芽糖淀粉酶基因(amyM)、解淀粉芽孢杆菌(Bacillus amyloliquefaciens)α-淀粉酶基因(amyQ)、地衣芽孢杆菌青霉素酶基因(penP)、枯草芽孢杆菌xylA和xylB基因和原核β-内酰胺酶基因(Villa-Kamaroff等人，1978，Proc.NatlAcad.Sci.USA 75：3727-3731)和tac启动子(DeBoer等人，1983，Proc.NatlAcad.Sci.USA 80：21-25)。更多的启动子在以下文献中描述：“Useful proteinsfrom recombinant bacteria(重组细菌的有用蛋白质)”，Scientific American，1980，242：74-94；和Sambrook等人，见上。

对于丝状真菌宿主细胞，用于指导本公开内容的核酸构建体的转录的合适启动子包括从以下获得的启动子：米曲霉(Aspergillus oryzae)TAKA淀粉酶、米黑根毛霉(Rhizomucor miehei)天冬氨酸蛋白酶、黑曲霉(Aspergillusniger)中性α-淀粉酶、黑曲霉酸稳定型α-淀粉酶、黑曲霉或泡盛曲霉(Aspergillus awamori)葡萄糖淀粉酶(glaA)、米黑根毛霉脂肪酶、米曲霉碱性蛋白酶、米曲霉丙糖磷酸异构酶、构巢曲霉(Aspergillus nidulans)乙酰胺酶和尖孢镰刀菌(Fusarium oxysporum)胰蛋白酶样蛋白酶(WO 96/00787)的基因以及NA2-tpi启动子(来自黑曲霉中性α-淀粉酶基因和米曲霉丙糖磷酸异构酶基因的启动子的杂合体)及其突变体、截短的和杂合启动子。

在酵母宿主中，有用的启动子可来自酿酒酵母烯醇酶(ENO-1)、酿酒酵母半乳糖激酶(GAL1)、酿酒酵母醇脱氢酶/甘油醛-3-磷酸脱氢酶(ADH2/GAP)和酿酒酵母3-磷酸甘油酸激酶的基因。用于酵母宿主细胞的其他有用的启动子由Romanos等人，1992，Yeast 8：423-488描述。

所述控制序列还可以是合适的转录终止序列即由宿主细胞识别以终止转录的序列。终止序列可操作地连接至编码多肽的核酸序列的3’末端。在选择的宿主细胞中是功能性的任何终止子均可用于本发明。

例如，用于丝状真菌宿主细胞的示例性转录终止子可由以下基因获得：米曲霉TAKA淀粉酶、黑曲霉葡萄糖淀粉酶、构巢曲霉邻氨基苯甲酸合成酶、黑曲霉α-葡萄糖苷酶和尖孢镰刀菌胰蛋白酶样蛋白酶。

用于酵母宿主细胞的示例性终止子可从酿酒酵母烯醇酶、酿酒酵母细胞色素C(CYC1)和酿酒酵母甘油醛-3-磷酸脱氢酶的基因获得。用于酵母宿主细胞的其他有用终止子由Romanos等人，1992(见上)描述。

所述控制序列还可以是合适的前导序列，即对经由宿主细胞翻译重要的mRNA的非翻译区。所述前导序列可操作地连接至编码多肽的核酸序列的5’末端。可使用在选择的宿主细胞中是功能性的任何前导序列。用于丝状真菌宿主细胞的示例性前导区从米曲霉TAKA淀粉酶和构巢曲霉丙糖磷酸异构酶的基因获得。用于酵母宿主细胞的合适前导区从酿酒酵母烯醇酶(ENO-1)、酿酒酵母3-磷酸甘油酸激酶、酿酒酵母α-因子和酿酒酵母醇脱氢酶/甘油醛-3-磷酸脱氢酶(ADH2/GAP)的基因获得。

所述控制序列还可以是多聚腺苷化序列，即可操作地连接至核酸序列的3’末端的序列，当所述序列被转录时，它被宿主细胞识别为向转录的mRNA添加多聚腺苷酸残基的信号。在选择的宿主细胞中是功能性的任何多聚腺苷化序列均可用于本发明。用于丝状真菌宿主细胞的示例性多聚腺苷化序列可来自米曲霉TAKA淀粉酶、黑曲霉葡萄糖淀粉酶、构巢曲霉邻氨基苯甲酸合成酶、尖孢镰刀菌胰蛋白酶样蛋白酶和黑曲霉α-葡萄糖苷酶的基因。用于酵母宿主细胞的有用多聚腺苷化序列由Guo和Sherman，1995，Mol Cell Bio 15：5983-5990描述。

所述控制序列还可以是编码连接至多肽的氨基末端的氨基酸序列并且指导编码的多肽进入细胞分泌途径的信号肽编码区。所述核酸序列的编码序列的5’端可内在地包含按翻译阅读框与编码分泌多肽的编码区的区段天然连接的信号肽编码区。可选地，所述编码序列的5’端可包括对所述编码序列是外源性的信号肽编码区。当所述编码序列未天然包含信号肽编码区时，外源性信号肽编码区可以是必需的。

可选地，所述外源性信号肽编码区可简单地替换天然的信号肽编码区以增强多肽的分泌。然而，指导表达多肽进入选择的宿主细胞的分泌途径的任何信号肽编码区均可用于本发明。

用于细菌宿主细胞的有效信号肽编码区是从NClB 11837芽孢杆菌麦芽糖淀粉酶、嗜热脂肪芽孢杆菌α-淀粉酶、地衣芽孢杆菌枯草杆菌蛋白酶、地衣芽孢杆菌β-内酰胺酶、嗜热脂肪芽孢杆菌中性蛋白酶(nprT、nprS、nprM)和枯草芽孢杆菌prsA的基因获得的信号肽编码区。进一步的信号肽由Simonen和Palva，1993，Microbiol Rev 57：109-137描述。

用于丝状真菌宿主细胞的有效信号肽编码区可以是从米曲霉TAKA淀粉酶、黑曲霉中性淀粉酶、黑曲霉葡萄糖淀粉酶、米黑根毛霉天冬氨酸蛋白酶、特异腐质霉(Humicola insolens)纤维素酶和柔毛腐质霉(Humicolalanuginosa)脂肪酶的基因获得的信号肽编码区。

用于酵母宿主细胞的有用信号肽可来自酿酒酵母α-因子和酿酒酵母转化酶的基因。其他有用的信号肽编码区由Romanos等人，1992，见上描述。

所述控制序列还可以是编码位于多肽氨基端的氨基酸序列的前肽编码区。所得的多肽被称为酶原(proenzyme)或多肽原(或在某些情况下为酶原(zymogen))。多肽原通常是无活性的并可通过前肽从多肽原中的催化或自身催化切割转化为成熟的活性多肽。所述前肽编码区可从枯草芽孢杆菌碱性蛋白酶(aprE)、枯草芽孢杆菌中性蛋白酶(nprT)、酿酒酵母α-因子、米黑根毛霉天冬氨酸蛋白酶和嗜热毁丝霉(Myceliophthora thermophila)乳糖酶的基因获得(WO 95/33836)。

当信号肽和前肽区都存在于多肽的氨基端时，前肽区位于邻近多肽的氨基端，而信号肽区位于邻近前肽区的氨基端。

还可期望添加调节序列，所述调节序列允许相对宿主细胞的生长调节多肽表达。调节系统的实例是响应于包括调节化合物的存在的化学或物理刺激而引起基因的表达开启或关闭的那些调节系统。在原核宿主细胞中，适合的调节序列包括lac、tac和trp操纵基因系统。在酵母宿主细胞中，适合的调节系统包括如ADH2系统或GAL1系统。在丝状真菌中，适合的调节序列包括TAKAα-淀粉酶启动子、黑曲霉葡萄糖淀粉酶启动子和米曲霉葡萄糖淀粉酶启动子。

调节序列的其他实例是允许基因扩增的那些。在真核系统中，这些包括在甲氨喋呤的存在下扩增的二氢叶酸盐还原酶基因和在重金属存在下扩增的金属硫蛋白基因。在这些情况下，编码本发明的KRED多肽的核酸序列与所述调节序列可操作地连接。

因此，在另一个方面中，本公开内容还涉及包括编码改进的酮还原酶多肽的多核苷酸或其变体和一种或多种表达调节区如启动子和终止子、复制起点等的重组表达载体，具体取决于引入载体的宿主的类型。上述的各种核酸和控制序列可连接在一起以产生重组表达载体，所述重组表达载体可包括一个或多个方便的限制位点以允许在这些位点插入或置换编码多肽的核酸序列。可选地，本公开内容的核酸序列可通过将所述核酸序列或包括所述序列的核酸构建体插入到适合的表达载体来表达。在构建所述表达载体中，所述编码序列位于载体中以使所述编码序列与适合的表达控制序列可操作地连接。

所述重组表达载体可以是任何载体(例如质粒或病毒)，其可方便地进行重组DNA程序，并可引起多核苷酸序列的表达。载体的选择通常将取决于载体与引入所述载体的宿主细胞的相容性。所述载体可以是线性或闭合环状质粒。

所述表达载体可以是自主复制载体，即作为染色体外实体存在的载体，例如质粒、染色体外元件、微型染色体或人工染色体，所述载体的复制不依赖于染色体复制。所述载体可包括任何保证自身复制的部件(means)。可选地，所述载体可以是在被引入到宿主细胞时，整合到基因组中并且与整合其的染色体一起复制的载体。此外，可使用一起包括引入到所述宿主细胞的基因组中的总DNA的单一载体或质粒或者两个或更多个载体或质粒或转座子(transposon)。

本发明的表达载体优选包含一种或多种选择标记基因，其允许转化细胞的容易选择。选择标记基因是其产物提供杀生物剂或病毒抗性、对重金属的抗性、营养缺陷体的原养型及类似性质的基因。细菌选择标记基因的实例是枯草芽孢杆菌或地衣芽孢杆菌的dal基因，或赋予抗生素抗性如氨苄西林、卡那霉素、氯霉素(实施例1)或四环素抗性的标记基因。用于酵母宿主细胞适合的标记基因是ADE2、HIS3、LEU2、LYS2、MET3、TRP1和URA3。

用于丝状真菌宿主细胞的选择标记基因包括但不限于amdS(乙酰胺酶)、argB(鸟氨酸氨甲酰转移酶)、bar(草胺膦乙酰转移酶)、hph(潮霉素磷酸转移酶)、niaD(硝酸还原酶)、pyrG(乳清酸核苷-5’-磷酸脱羧酶)、sC(硫酸腺苷酰转移酶(sulfate adenyltransferase))和trpC(邻氨基苯甲酸合成酶)、及其等效物。用于曲霉细胞的实施方案包括构巢曲霉或米曲霉的amdS和pyrG基因和吸水链霉菌(Streptomyces hygroscopicus)的bar基因。

本发明的表达载体优选包括允许所述载体整合至宿主细胞基因组或所述载体在细胞中不依赖于基因组而自主复制的元件。对于整合至宿主细胞基因组的情况，所述载体可依赖于编码所述多肽的核酸序列或载体的任何其他元件而通过同源或非同源重组将所述载体整合到基因组中。

可选地，所述表达载体可包括用于指导通过同源重组整合至宿主细胞基因组的另外核酸序列。所述另外核酸序列使所述载体以在染色体中的精确位置整合到宿主细胞基因组中。为了增加在精确位置整合的可能性，整合元件应优选包含足够数目的核酸如100至10,000个碱基对、优选400至10,000个碱基对、且最优选800至10,000个碱基对，所述核酸与对应的靶序列具有高度同源性以增加同源重组的可能性。所述整合元件可以是与宿主细胞的基因组中的靶序列具有同源性的任何序列。此外，所述整合元件可以是非编码的或编码的核酸序列。另一方面，所述载体可通过非同源重组整合到宿主细胞的基因组中。

对于自主复制的情况，所述载体可进一步包括在使所述载体在相关宿主细胞中自主复制的复制起点。细菌复制起点的实例是P15A ori(如图5的质粒所示)、或允许在大肠杆菌中复制的质粒pBR322、pUC19、pACYC177(所述质粒具有P15A ori)或pACYC184的复制起点以及允许在芽孢杆菌中复制的pUB110、pE194、pTA1060或pAM.β.1的复制起点。用于酵母宿主细胞的复制起点的实例是2微米复制起点、ARS1、ARS4、ARS1和CEN3的组合以及ARS4和CEN6的组合。所述复制起点可以是具有突变的复制起点，所述突变使其在宿主细胞中的功能具有温度敏感性(参见例如Ehrlich，1978，Proc Natl Acad Sci.USA 75：1433)。

本发明的核酸序列的多于一个拷贝可插入到宿主细胞中以增加基因产物的产生。核酸序列的拷贝数的增加可通过整合序列的至少一个附加拷贝到宿主细胞基因组中或通过随核酸序列包括可扩增的选择标记基因(如果细胞包含选择标记基因的扩增拷贝，则可通过在适合的选择剂的存在下培养所述细胞来选择核酸序列的附加拷贝)来获得。

用于本发明的很多表达载体是商业上可得的。适合的商业表达载体包括来自Sigma-A1drich Chemicals，St.Louis MO.的p3xFLAGTM^TM表达载体，它包括用于在哺乳动物宿主细胞中表达的CMV启动子和hGH多聚腺苷化位点以及用于在大肠杆菌中扩增的pBR322复制起点和氨苄西林抗性标记基因。其他适合的表达载体是从Stratagene，LaJoIIa CA商业上可得的pBluescriptII SK(-)和pBK-CMV以及衍生自pBR322(Gibco BRL)、pUC(Gibco BRL)、pREP4、pCEP4(Invitrogen)或pPoly的质粒(Lathe等人，1987，Gene 57：193-201)。

6.4用于表达酮还原酶多肽的宿主细胞

在另一个方面中，本公开内容提供了包括编码本公开内容的改进酮还原酶多肽的多核苷酸的宿主细胞，所述多核苷酸与用于在宿主细胞中表达酮还原酶的一个或多个控制序列可操作地连接。用于表达由本发明的表达载体编码的KRED多肽的宿主细胞在本领域中众所周知，并包括但不限于细菌细胞如大肠杆菌、链霉菌(Sreptomyces)和鼠伤寒沙门氏菌(Salmonellatyphimurium)细胞；真菌细胞如酵母细胞(例如酿酒酵母或毕赤酵母(Pichiapastoris)(ATCC登录号201178))；昆虫细胞如果蝇(Drosophila)S2和夜蛾(Spodoptera)Sf9细胞；动物细胞如CHO、COS、BHK、293和Bowes黑素瘤细胞；和植物细胞。上述宿主细胞的适合的培养基和生长条件在本领域中众所周知。

用于表达酮还原酶的多核苷酸可通过本领域中已知的各种方法引入到细胞。技术包括电穿孔、生物射弹粒子轰击(biolistic particlebombardment)、脂质体介导的转染、氯化钙转染和原生质融合以及其他技术。用于将多核苷酸引入到细胞中的各种方法对熟练的技术人员来说是明显的。

示例性宿主细胞是如实施例1所述的大肠杆菌W3110。所述表达载体通过将编码改进酮还原酶的多核苷酸可操作地连接到质粒pCK110900中，而将所述质粒可操作地连接到处于lacI抑制子控制下的lac启动子来构建。所述表达载体还包含P15a复制起点和氯霉素抗性基因。在大肠杆菌W3110中包含主题多核苷酸的细胞通过使所述细胞经历氯霉素选择而分离。

6.5产生工程酮还原酶多肽的方法

为了制备本公开内容的改进KRED多核苷酸和多肽，从酿酒酵母中获得了催化还原反应的天然存在的酮还原酶。在一些实施方案中，对母体多核苷酸序列进行密码子优化以增强酮还原酶在特定宿主细胞中的表达。作为例证，基于Genbank数据库中可得的酿酒酵母KRED序列(ydl)的已知多肽序列(NP_010159；GI：6320079)从由42个核苷酸组成的寡核苷酸构建了编码酿酒酵母的野生型KRED多肽(ydl)的母体多核苷酸序列。对所述母体多核苷酸序列(指定为SEQ ID NO：1)进行密码子优化以在大肠杆菌中表达，将所述密码子优化的多核苷酸克隆到表达载体pCK110900的Sfil克隆位点(如图5中所述)，将所述酮还原酶基因的表达置于1ac启动子和lacI抑制子基因的控制下。所述表达载体还包含P15A复制起点和氯霉素抗性基因。鉴定在大肠杆菌W3110中表达活性酮还原酶的克隆并且测序所述基因以证实它们的同一性。命名为ydlC的序列(SEQ ID NO：1)是用作所有试验和从酿酒酵母酮还原酶进化而来的工程酮还原酶的文库构建的起始点的母体序列。

所述工程酮还原酶可通过使编码天然存在的酮还原酶的多核苷酸经历诱变和/或定向进化方法而获得。示例性定向进化技术是诱变和/或DNA改组，如Stemmer，1994，Proc Natl Acad Sci USA 91：10747-10751；WO95/22625；WO 97/0078；WO 97/35966；WO 98/27230；WO 00/42651；WO 01/75767和美国专利6,537,746中所述。可使用的其他定向进化程序包括交错延伸过程(staggered extension process)(StEP)、体外重组(Zhao等人，1998，Nat.Biotechnol.16：258-261)、诱变PCR(Caldwell等人，1994，PCRMethods Appl.3：S136-S140)和盒式诱变(Black等人，1996，Proc Natl AcadSci USA 93：3525-3529)以及其他程序。

对诱变处理后获得的克隆进行筛选以得到具有期望的改进酶性质的工程酮还原酶。从表达文库测量酶活性可使用监控NADH或NADPH浓度的减少率(通过吸光度或荧光的减少)(因为它转化成了NAD⁺或NADP⁺)的标准生物化学技术来进行。在此反应中，当酮还原酶将酮底物还原成对应的羟基时，NADH或NADPH被所述酮还原酶消耗(氧化)。如由吸光度或荧光的减少所测量的，每单位时间NADH或NADPH浓度的减少率表明固定量的溶解产物(或由此制备的冻干粉末)中KRED多肽的相对(酶)活性。实施例11公开了酮还原酶活性的示例性生物化学测定。当期望的改进酶性质为热稳定性时，如在实施例12中，酶活性可在使酶制品经受规定的温度并且测量热处理后剩余的酶活性的量之后来测量。然后分离包含编码酮还原酶的多核苷酸的克隆，对所述克隆进行测序以鉴定核苷酸序列变化(如果有)，并使用所述克隆在宿主细胞中表达所述酶。

当已知工程多肽的序列时，编码所述酶的多核苷酸可根据已知的合成方法通过标准固相方法来制备。在一些实施方案中，可单独合成多达约100个碱基的片段，然后连接(例如通过酶或化学连接(litigation)方法或聚合酶介导的方法)所述片段以形成任何期望的连续序列。例如，本发明的多核苷酸和寡核苷酸可使用以下方法通过化学合成来制备：例如由Beaucage等人，1981，Tet Lett 22：1859-69描述的经典亚磷酰胺法或由Matthes等人，1984，EMBO J.3：801-05描述的方法(例如它通常在自动合成方法中实施)。根据所述亚磷酰胺法，在DNA自动合成仪中合成寡核苷酸并将其纯化、退火、连接并克隆至适合载体中。此外，几乎任何核酸均可从多种商业来源的任一种获得，所述商业来源如The Midland Certified Reagent Company，Midland，TX、The Great American Gene Company，Ramona，CA、ExpressGenInc.Chicago，IL、Operon Technologies Inc.，Alameda，CA及很多其他商业来源。

在宿主细胞中表达的工程酮还原酶可使用任何一种或多种的众所周知的蛋白纯化技术从细胞和/或培养基回收，所述蛋白纯化技术包括溶菌酶处理、超声、过滤、盐析、超速离心和色谱法以及其他方法。合适的细胞裂解液和蛋白质从细菌如大肠杆菌中的高效提取液是以St.Louis MO的Sigma-Aldrich的商标名称CelLytic B^TM从商业上可获得的。

分离酮还原酶多肽的色谱技术包括反相色谱法、高效液相色谱法、离子交换色谱法、凝胶电泳和亲合色谱法以及其他方法。纯化具体酶的条件部分取决于如净电荷、疏水性、亲水性、分子量、分子形状等的因素并且对本领域技术人员来说是明显的。

在一些实施方案中，可使用亲合技术分离改进的酮还原酶。对于亲合色谱法纯化，可使用特异性结合酮还原酶多肽的任何抗体。对于抗体的制备，包括但不限于兔、小鼠、大鼠等的各种宿主动物可通过用化合物注射来免疫。所述化合物可借助于侧链官能团或连接至侧链官能团的连接体与合适的载体如BSA连接。取决于宿主种类，多种佐剂可用于增加免疫应答，所述佐剂包括但不限于弗氏佐剂(完全和不完全)、矿物凝胶如氢氧化铝、表面活性物质如溶血卵磷脂、普卢兰尼克(pluronic)多元醇、聚阴离子、肽、油乳剂、匙孔血蓝蛋白、二硝基苯酚和潜在有用的人佐剂如BCG(卡介苗(bacilli Calmette Guerin))和短小棒状杆菌(Corynebacterium parvum)。

从细胞溶解产物中回收KRED多肽以应用于化学过程中的示例性过程在实施例2中公开。

6.6使用工程酮还原酶的方法及由其制备的化合物

本文所述的工程酮还原酶催化根据结构式(Ia)的5-羟基-3-氧代己酸酯对映体的还原，以产生对应的顺式3，5-二羟基己酸酯化合物，

其中X和R¹如前文所定义。如熟练的技术人员应认识到的，在结构式(I)化合物的5-位上的碳是手性的。因此，所述化合物可以以两种不同的对映体形式存在：上文结构式(Ia)的对映体和结构式(Ib)的对映体(entantiomer)：

熟练的技术人员还应认识到，当在3-位的氧代基团被还原成羟基时，所得的3，5-二羟基酯的3-位碳原子也是手性的。因此，结构式(Ia)和(Ib)的对映体的每一个都可产生两种不同的还原产物：顺式非对映体和反式非对映体。经还原对映体(Ia)而产生的顺式和反式非对映体分别如下文化合物(IIa)和(IIb)示例，而经还原对映体(Ib)而产生的那些分别如化合物(IIc)和(IId)示例：

有关3-碳的绝对构型在上面结构图中示例。有关5-碳的绝对构型的R-或S-命名将依赖于X的特征性(identity)。当X是氰基时，5-碳在结构(Ia)、(IIa)和(IIb)中命名为R-，而在结构(Ib)、(IIc)和(IId)中命名为S-。当X是卤素或羟基时，5-碳在结构(Ia)、(IIa)和(IIb)中命名为S-，而在结构(Ib)、(IIc)和(IId)中命名为R-。这取决于命名R或S的惯例，其在X＝氰基和X＝卤素或羟基之间颠倒。

在一些实施方案中，底物(Ia)具有高对映纯度(enantiopurity)，基本上不含(Ib)。

在一些实施方案中，所述还原反应也具有高度的非对映选择性，产生非对映体纯度≥99.95％的结构式(IIa)的顺式非对映体，即≤0.05％的结构式(IIb)的反式非对映体(即≥99.9％非对映体过量)。本文所述的工程酮还原酶的很多实施方案显示甚至更高的立体选择性。例如，在用表2中引用的工程酮还原酶进行的6-氰基-(5R)-羟基-3-氧代己酸叔丁酯(结构式(Ia)，X＝CN，R¹＝叔丁基)的反应中，观察到≥99.99％的6-氰基-(3R，5R)-二羟基己酸酯(结构式(IIa)，X＝CN，R¹＝叔丁基)非对映选择性。因此，非对映选择性还原范围≥99.9％、≥99.91％、≥99.92％、≥99.93％、≥99.94％、≥99.95％、≥99.96％、≥99.97％、≥99.98％和甚至≥99.99％的非对映选择还原可用本文所述的工程酮还原酶容易实现。

在由本文所述的工程酮还原酶催化的还原反应中观察到的高度的非对映选择性使得不需进行手性分离或分离步骤就能够产生大致非对映体纯的(即基本上不含所有其他非对映体)的结构式(IIa)的顺式3，5-二羟基己酸酯的制品。因为利用高度对映纯的5-羟基-3-氧代己酸酯(Ia)起始物该反应可以以高产率进行，所以本公开内容在需要最低限度的纯化或不需纯化下就能够制备大致非对映体纯的结构式(IIa)的顺式3，5-二羟基己酸酯。与本公开内容相反，现有的还原方法(例如美国专利6,596,879)生成3-4％(IIb)(X＝CN，R¹＝叔丁基)，其是油，然后将其反应以形成(6-氰甲基-2，2-二甲基-1，3-二噁烷-4-乙酸叔丁酯)(X＝CN，R¹＝叔丁基，R³、R⁴＝甲基)即一种结晶化合物。在现有的已知方法中，通过结晶降低(IIb)的含量而提高纯度，这导致(IIa)的产率损失。

用本文所述的工程酮还原酶获得的高非对映体纯度的还原产物在图6中示例，图6比较了从商业上可得的结晶(6R)-氰甲基-2，2-二甲基-1，3-二噁烷-(4R)-乙酸叔丁酯(结构式(IVa)，X＝CN，R¹＝叔丁基，R³、R⁴＝甲基)(Aldrich，St.Louis，MO)制备的6-氰乙基-(3R，5R)-二羟基己酸叔丁酯(结构式(IIa)，X＝CN，R¹＝叔丁基)的LC/MS/MS色谱图与使用本公开内容的工程酮还原酶从6-氰基-(5R)-羟基-3-氧代己酸叔丁酯(结构式(Ia)，X＝CN，R¹＝叔丁基)制备的粗6-氰基-(3R，5R)-二羟基己酸叔丁酯油的LC/MS/MS色谱图。如在图6中示例，与从商业上可得的包含少于约0.1％的不期望的(3S，5R)非对映体(IIb)的结晶(6R)-氰甲基-2，2-二甲基-1，3-二噁烷-(4R)-乙酸叔丁酯制备的(6R)-氰乙基-3，5-二羟基己酸叔丁酯样品相比，使用本公开内容的工程酮还原酶制备的粗6-氰基-(3R，5R)-二羟基己酸叔丁酯油包含可能不超过0.005％的不期望(3S，5R)非对映体。

同样地，观察到了(6R)-氰甲基-2，2-二甲基-1，3-二噁烷-(4R)-乙酸叔丁酯的非对映体纯度的显著差异(参见实施例28和图7)。比较商业上可获得的结晶TBIN((4R，顺)-1，1-二甲基-6-氰甲基-2，2-二甲基-1，3-二噁烷-4-乙酸酯))和由使用本发明的工程酮还原酶制备的粗C7二醇制备的粗的、提取的但未结晶的TBIN的立体异构体纯度的GC/MS色谱图在图7中示例。同样地，由使用本公开内容的方法制备的C7二醇生成的阿托伐他汀的非对映体纯度大于目前商业上制品中存在的阿托伐他汀的非对映体纯度(例如

丸剂存在0.03％阿托伐他汀非对映体)。

如本文所用，当特定的立体异构体与存在于化合物的任何其他立体异构体相比以过量存在时，该化合物即“富集”该立体异构体。富集特定立体异构体的化合物通常包括至少约60％、70％、80％、90％或甚至更多的指定立体异构体。如下文将更详细地论述的，特定立体异构体的富集的量可使用本领域技术人员通常使用的常规分析方法来确定。

在一些实施方案中，不期望的立体异构体的量可少于10％，例如少于9％、少于8％、少于7％、少于6％、少于5％、少于4％、少于3％、少于2％、少于1％或甚至少于0.9％、0.8％、0.7％、0.6％、0.5％、0.4％、0.2％或0.1％。包含至少约99.5％或更多的期望立体异构体的立体异构富集的化合物在本文称作“大致纯的”立体异构体。在一些实施方案中，以特定的立体异构体大致纯的化合物包含大于99.6％、99.7％、99.8％、99.9％、99.91％、99.92％、99.93％、99.94％、99.95％、99.96％、99.97％、99.98％或甚至99.99％的所述特定立体异构体。包含≥99.99％的期望立体异构体的立体异构富集的化合物在本文称作“纯”立体异构体。

本文所述的任何手性化合物的立体异构体纯度可使用本领域已知的常规分析方法来测定或确认。用于评价本文所述的合成中间体的非对映异构体纯度的高灵敏LC/MS和GC/MS法在实施例5-7中提供。用于测定阿托伐他汀的非对映体纯度的方法在Ertürk等人，2003，J Pharm Biomed Anal.33(5)：1017-23中给出。

如本领域技术人员已知，酮还原酶催化的还原反应通常需要辅因子。由本文所述的工程酮还原酶催化的还原反应也通常需要辅因子，尽管工程酮还原酶的很多实施方案需要比野生型酮还原酶催化的反应少得多的辅因子。如本文所用，术语“辅因子”是指与酮还原酶组合起作用的非蛋白化合物。适于与本文所述的工程酮还原酶使用的辅因子包括但不限于NADP⁺(烟酰胺腺嘌呤二核苷酸磷酸)、NADPH(NADP⁺的还原形式)、NAD⁺(烟酰胺腺嘌呤二核苷酸)和NADH(NAD⁺的还原形式)。下面的反应式(1)示例了利用NADH或NADPH作为辅因子的酮还原酶(“KRED”)催化的还原反应的实施方案，NADH或NADPH通过命名NAD(P)H表示为替代物：

如示例，将辅因子的还原形式加至反应混合物中。还原型NAD(P)H形式可使用辅因子再生系统任选地从氧化型NAD(P)⁺形式再生。

术语“辅因子再生系统”是指参与还原辅因子的氧化型形式(例如NADP⁺至NADPH)的反应的一组反应物。通过5-羟基-3-氧代己酸酯的酮还原酶催化还原而氧化的辅因子经由辅因子再生系统以还原形式再生。辅因子再生系统包括是还原氢等价物的来源并能还原辅因子的氧化形式的化学计量的还原剂。所述辅因子再生系统可进一步包括催化还原剂还原辅因子氧化形式的催化剂，例如酶催化剂。分别从NAD⁺或NADP⁺再生NADH或NADPH的辅因子再生系统为本领域已知，并可用于本文所述的方法。

可使用的合适的示例性辅因子再生系统包括但不限于葡萄糖和葡萄糖脱氢酶、甲酸(formate)和甲酸脱氢酶、葡萄糖-6-磷酸和葡萄糖-6-磷酸脱氢酶、仲醇(例如异丙醇)和仲醇脱氢酶、亚磷酸酯和亚磷酸酯脱氢酶、分子氢和氢化酶及类似辅因子再生系统。这些系统可与作为辅因子的NADP⁺/NADPH或NAD⁺/NADH组合使用。使用氢化酶的电化学再生也可用作辅因子再生系统。参见，例如美国专利第5,538,867和6,495,023号，其均通过引用并入本文。包括金属催化剂和还原剂(例如分子氢或甲酸)的化学辅因子再生系统也是适合的。参见，例如PCT公布WO 2000/053731，其通过引用并入本文。

术语“葡萄糖脱氢酶”和“GDH”在本文可互换使用，是指催化D-葡萄糖和NAD⁺或NADP⁺分别转化成葡萄糖酸和NADH或NADPH的NAD⁺或NADP⁺依赖性酶。下面的反应式(2)描述了通过葡萄糖脱氢酶催化的葡萄糖还原NAD⁺或NADP⁺。

适用于实施本文所述方法的葡萄糖脱氢酶包括天然存在的葡萄糖脱氢酶和非天然存在的葡萄糖脱氢酶两者。天然存在的葡萄糖脱氢酶的编码基因已在文献中报道。例如，枯草芽孢杆菌61297GDH基因在大肠杆菌中表达，并报道它显示与在其天然宿主中生成的酶相同的理化性质(Vasantha等人，1983，Proc.Natl.Acad.Sci.USA 80：785)。对应于Genbank登录号M12276的枯草芽孢杆菌GDH基因的基因序列由Lampel等人，1986，J.Bacteriol.166：238-243报道，并由Yamane等人，1996，Microbiology142：3047-3056作为Genbank登录号D50453以校正的形式报道。天然存在的GDH基因还包括编码来自蜡状芽孢杆菌(B.cereus)ATCC 14579(Nature，2003，423：87-91；Genbank登录号AE017013)和巨大芽孢杆菌(B.megaterium)(Eur.J.Biochem.，1988，174：485-490，Genbank登录号X12370；J.Ferment.Bioeng.，1990，70：363-369，Genbank登录号GI216270)的GDH的那些基因。芽孢杆菌(Bacillus sp.)的葡萄糖脱氢酶在PCT公布WO 2005/018579中以SEQ ID NO：10和12(分别由对应于所述PCT公布的SEQ ID NO：9和11的多核苷酸序列编码)提供，其公开内容通过引用并入本文。

非天然存在的葡萄糖脱氢酶可使用已知的方法如诱变、定向进化及类似方法来产生。具有合适活性的GDH酶(不管是天然存在还是非天然存在)可使用PCT公布WO 2005/018579(其公开内容通过引用并入本文)的实施例4中描述的测定来容易地鉴定。示例性非天然存在的葡萄糖脱氢酶以SEQ ID NO：62、64、66、68、122、124和126在PCT公布WO2005/018579中提供。编码它们的多核苷酸序列分别以SEQ ID NO：61、63、65、67、121、123和125在PCT公布WO 2005/018579中提供。所有这些序列都通过引用并入本文。适用于本文公开的酮还原酶催化的还原反应的另外的非天然存在葡萄糖脱氢酶在美国申请公布号2005/0095619和2005/0153417中提供，其公开内容通过引用并入本文。

用于本文所述的酮还原酶催化的还原反应的葡萄糖脱氢酶可在PCT公布WO 2005/018579的实施例4描述的测定中显示至少约10μmol/分钟/mg、有时至少约10²μmol/分钟/mg或约10³μmol/分钟/mg、约10⁴μmol/分钟/mg或更高的活性。

当葡萄糖和葡萄糖脱氢酶用作辅因子再生系统时，由于5-羟基-3-氧代己酸酯底物被工程酮还原酶和NADH或NADPH还原，故所得的NAD⁺或NADP⁺通过用葡萄糖脱氢酶将葡萄糖偶联氧化成葡萄糖酸而还原。净反应由反应式(3)描述，反应式(3)是反应式(1)和(2)的总和：

本文所述的酮还原酶催化的还原反应一般在溶剂中进行。适合的溶剂包括水、有机溶剂(例如乙酸乙酯、乙酸丁酯、1-辛醇(octacnol)、庚烷、辛烷、甲基叔丁醚(MTBE)、甲苯及类似有机溶剂)、离子液体(例如1-乙基-4-甲基咪唑四氟硼酸盐、1-丁基-3-甲基咪唑四氟硼酸盐，1-丁基-3-甲基咪唑六氟磷酸盐及类似离子液体)。在一些实施方案中，可使用包括水和水性共溶剂系统的水性溶剂(aqueous solvent)。

示例性的水性共溶剂系统具有水和一种或多种有机溶剂。一般来说，选择水性共溶剂系统的有机溶剂组分以使它不完全使酮还原酶失活。合适的共溶剂系统可通过利用酶活性测定(如在实施例中描述的那些测定)，在候选溶剂系统中用感兴趣的5-羟基-3-氧代己酸酯测量特定工程酮还原酶的酶活性而容易地鉴定。

水性共溶剂系统的有机溶剂组分可与水性组分混溶而提供单一液相，或可与水性组分部分混溶或不相混溶而提供两种液相。一般来说，当使用水性共溶剂系统时，选择它是双相性的，其中水分散在有机溶剂中，或者相反。一般来说，当利用水性共溶剂系统时，期望选择可从水相容易分离的有机溶剂。一般来说，水与有机溶剂在共溶剂系统中的比率通常范围为约90∶10至约10∶90(v/v)有机溶剂比水、以及80∶20至20∶80(v/v)之间有机溶剂比水。所述共溶剂系统可在加入到反应混合物前预先形成，或它可在反应容器中原位形成。

水性溶剂(水或水性共溶剂系统)可以是pH缓冲的或无缓冲的。将5-羟基-3-氧代己酸酯还原为对应的3，5-二羟基己酸酯可在约5或5以上的pH进行。一般来说，所述还原在约10或10以下的pH下、通常在约5至约10的范围中进行。在一些实施方案中，所述还原在约9或9以下的pH下、通常在约5至约9的范围中进行。在一些实施方案中，所述还原在约8或8以下的pH下、经常在约5至约8的范围中、并且通常在约6至约8的范围中进行。所述还原还可在约7.8或7.8以下、或者7.5或7.5以下的pH下进行。可选地，所述还原可在中性pH即约7下进行。

在还原反应的过程期间，反应混合物的pH可变化。反应混合物的pH可通过在反应过程期间加入酸或碱而维持在期望的pH或在期望的pH范围内。可选地，pH可通过使用包括缓冲液的水性溶剂来控制。维持期望的pH范围的合适缓冲液在本领域中已知，并包括例如磷酸盐缓冲液、三乙醇胺缓冲液及类似缓冲液。还可使用缓冲与酸或碱添加的组合。

当使用葡萄糖/葡萄糖脱氢酶辅因子再生系统时，如果不以别的方式中和所得的水性葡萄糖酸，那么如反应式(3)中表示的葡萄糖酸(pKa＝3.6)的共同产生(co-production)导致反应混合物的pH下降。反应混合物的pH可通过标准缓冲技术(其中缓冲液中和葡萄糖酸直到所提供的缓冲容量)或者通过在转化过程同时发生的碱添加而维持在期望的水平。也可使用缓冲和碱添加的组合。维持期望的pH范围的适合缓冲液如上述。用于中和葡萄糖酸的合适碱是有机碱如胺、醇盐及类似有机碱，和无机碱如氢氧化盐(例如NaOH)、碳酸盐(例如NaHCO₃)、碳酸氢盐(例如K₂CO₃)、碱性磷酸盐(例如K₂HPO₄、Na₃PO₄)及类似无机碱。与转化过程同时发生的碱添加可在监控反应混合物pH的同时手动进行，或者更方便地通过使用自动滴定器作为恒pH器(pH stat)来进行。部分缓冲容量和碱添加的组合也可用于过程控制。

在当通过缓冲或通过在转化过程内添加碱维持pH的此类还原反应中，水性葡萄糖酸盐而不是水性葡萄糖酸是全过程的产物。例如，反应式(4)表示当在反应过程内加入水性氢氧化钠(Na⁺+OH^-)以维持初始pH低于约5或5以上的全过程。

当使用碱添加以中和酮还原酶催化的还原反应期间释放的葡萄糖酸时，转化进程可通过维持pH所添加的碱的量来监控。通常地，在还原过程内向无缓冲或部分缓冲的反应混合物添加的碱是以水性溶液添加的。

在一些实施方案中，当所述过程使用宿主生物体的全细胞来进行时，全细胞可天然地提供辅因子。可选地或组合地，所述细胞可天然或重组地提供葡萄糖脱氢酶。

术语“甲酸脱氢酶”和“FDH”在本文可互换使用，是指催化甲酸和NAD⁺或NADP⁺分别转化成二氧化碳和NADH或NADPH的NAD⁺或NADP⁺依赖性酶。适于在本文所述的酮还原酶催化还原反应中作为辅因子再生系统使用的甲酸脱氢酶包括天然存在的甲酸脱氢酶和非天然存在的甲酸脱氢酶两者。甲酸脱氢酶包括对应于PCT公布WO 2005/018579的SEQ ID NO：70(假单胞菌(Pseudomonas sp.))和72(假丝酵母(Candidaboidinii))的那些甲酸脱氢酶，其分别由对应于PCT公布2005/018579的SEQID NO：69和71的多核苷酸序列编码，所述PCT公布的公开内容通过引用并入本文。在本文所述方法中所用的甲酸脱氢酶(不管是天然存在或非天然存在的)可显示至少约1μmol/分钟/mg、有时至少约10μmol/分钟/mg或至少约10²μmol/分钟/ng、直到约10³μmol/分钟/mg或更高的活性，并可在PCT公布WO 2005/018579的实施例4所述的测定中容易地筛选活性。

如本文所用，术语“甲酸”是指甲酸阴离子(HCO₂ ^-)、甲酸(HCO₂H)、及其混合物。甲酸可以以盐(通常碱或铵盐的形式，例如，HCO₂Na、KHCO₂NH₄及类似形式)、以甲酸(通常水性甲酸)或其混合物的形式提供。甲酸是中度酸。在位于其pKa(水中pKa＝3.7)的若干个pH单位内的水性溶液中，甲酸以平衡浓度下的HCO₂ ^-和HCO₂H两者存在。在高于约pH 4的pH值下，甲酸主要以HCO₂ ^-存在。当甲酸(formate)以甲酸(formic acid)提供时，通常通过添加碱对反应混合物进行缓冲或使其酸性下降以提供期望的pH-通常为约pH 5或5以上。用于中和甲酸的合适碱包括但不限于有机碱如胺、醇盐及类似有机碱，和无机碱如氢氧化盐(例如NaOH)、碳酸盐(例如NaHCO₃)、碳酸氢盐(例如K₂CO₃)、碱式磷酸盐(例如K₂HPO₄、Na₃PO₄)及类似无机碱。

对于高于约pH 5的pH值，在此pH值下甲酸主要以HCO₂ ^-存在，下面的反应式(5)描述了通过甲酸脱氢酶催化的甲酸对NAD⁺或NADP⁺的还原。

当甲酸和甲酸脱氢酶用作辅因子再生系统时，5-羟基-3-氧代己酸酯被酮还原酶和NADH或NADPH还原，所得的NAD⁺或NADP⁺通过由甲酸脱氢酶将甲酸偶联氧化成二氧化碳而得以还原。净反应的实施方案由反应式(6)描述，反应式(6)是反应式(1)和(5)的总和：

反应式(6)显示，当在pH高于约pH 5的水性溶液中将甲酸/甲酸脱氢酶辅因子再生系统用于5-羟基-3-氧代己酸酯的还原时，溶液中的质子被消耗并且如果未以其他方式缓冲或再酸化反应混合物，那么反应使得反应混合物的pH升高。反应混合物的pH可通过标准缓冲技术(其中所述缓冲液释放质子直到所提供的缓冲容量)或者通过在转化过程同时发生的酸添加而维持在期望的水平。维持pH而在反应过程期间添加的合适酸包括有机酸如羧酸、磺酸、磷酸及类似有机酸，矿物酸如氢卤酸(如盐酸)、硫酸、磷酸及类似矿物酸，酸性盐如二氢磷酸盐(例如KH₂PO₄)、硫酸氢盐(例如NaHSO₄)及类似酸性盐。一些实施方案利用甲酸，其中甲酸浓度和溶液的pH都得以维持。例如，反应式(7)表示当在反应过程内添加甲酸(HCO₂H)以维持起始pH高于约pH 5的全过程。尽管甲酸在反应混合物中主要以HCO₂ ^-存在，但是HCO₂ ^-浓度得以维持而净转化消耗添加的甲酸。

当在使用甲酸/甲酸脱氢酶辅因子再生系统的还原反应期间应用酸添加来维持pH时，转化的进程可通过维持pH所添加的酸的量来监控。通常地，在转化过程中向无缓冲或部分缓冲的反应混合物添加的酸是以水性溶液添加的。

术语“仲醇脱氢酶”和“sADH”在本文可互换使用，是指催化仲醇和NAD⁺或NADP⁺分别转化为酮和NADH或NADPH的NAD⁺或NADP⁺依赖性酶。下面的反应式(8)描述了NAD⁺或NADP⁺经仲醇的还原，通过异丙醇示例。

适于在本文所述的酮还原酶催化的还原反应中作为辅因子再生系统使用的仲醇脱氢酶包括天然存在的仲醇脱氢酶和非天然存在的仲醇脱氢酶两者。天然存在的仲醇脱氢酶包括来自布氏热厌氧菌(Thermoanerobiumbrockii)、红平红球菌(Rhodococcus etythropolis)、克菲尔乳酸杆菌(Lactobacillus kefiri)和短乳杆菌(Lactobacillus brevis)的已知醇脱氢酶，而非天然存在的仲醇脱氢酶包括由其衍生的工程醇脱氢酶。用于本文所述方法的仲醇脱氢酶(不管是天然存在或非天然存在的)可显示至少约1μmol/分钟/mg、有时至少约10μmol/分钟/mg或至少约10²μmol/分钟/mg、直到约10³μmol/分钟/mg或更高的活性。

合适的仲醇包括低级仲链烷醇和芳基-烃基甲醇(carbinol)。低级仲醇的实例包括异丙醇、2-丁醇、3-甲基-2-丁醇、2-戊醇、3-戊醇、3，3-二甲基-2-丁醇、及类似低级仲醇。在一个实施方案中，所述仲醇是异丙醇。合适的芳基-烃基甲醇包括未取代的和取代的1-芳基乙醇。

当仲醇和仲醇脱氢酶用作辅因子再生系统时，由于5-羟基-3-氧代己酸酯底物被工程酮还原酶和NADH或NADPH还原，因此所得的NAD⁺或NADP⁺通过由仲醇脱氢酶将仲醇偶联氧化成酮而被还原。净反应由用异丙醇示例的反应式(9)描述，反应式(9)是反应式(1)和(8)的总和：

熟练的技术人员应理解，酮和醇分别到对应的醇和酮的此反应是可逆的，并将达到平衡。发明人发现正向反应是热力学上有利的，并仅需要中等过量的异丙醇即可在平衡时获得3-氧代己酸酯到期望的3，5-二羟基己酸酯的高转化。通常地，向反应提供的仲醇与3-氧代己酸酯的摩尔比在1至20的范围内。在一些实施方案中，此摩尔比为1至10、1至5或1至2。

某些工程酮还原酶还具有使仲醇还原剂脱氢的活性。在一些使用仲醇作为还原剂的实施方案中，工程酮还原酶和仲醇脱氢酶是同一种酶。

在使用辅因子再生系统进行本文所述酮还原酶催化还原反应的实施方案时，最初可提供氧化型或还原型形式的辅因子。如上所述，所述辅因子再生系统将氧化型辅因子转化成其还原型形式，然后所述还原型形式用于将酮还原酶底物(即5-羟基-3-氧代己酸酯)还原成对应的3，5-二羟基己酸酯。

在一些实施方案中，不使用辅因子再生系统。对于不使用辅因子再生系统而进行的还原反应，辅因子以还原型形式加入到反应混合物。

在进行本文所述的对映选择性还原反应中，工程酮还原酶和包括任选的辅因子再生系统的任何酶可以以纯化酶、用编码所述酶的基因转化的全细胞和/或这些细胞的细胞提取物和/或溶解产物的形式被添加到反应混合物。编码工程酮还原酶和任选的辅因子再生酶的基因可分别转化入宿主细胞或一起转化入相同的宿主细胞。例如，在一些实施方案中，一组宿主细胞可用编码工程酮还原酶的基因转化，而另一组可用编码辅因子再生酶的基因转化。两组转化的细胞可在反应混合物中以全细胞的形式或以由此衍生的溶解产物或提取物的形式一起利用。在其他的实施方案中，宿主细胞可用编码工程酮还原酶和辅因子再生酶的基因转化。

用编码工程酮还原酶和/或任选的辅因子再生酶或其细胞提取物和/或溶解产物的基因转化的全细胞可以多种不同的形式使用，所述形式包括固体(例如冻干、喷雾干燥及类似形式)或半固体(例如粗制糊剂)。

所述细胞提取物或细胞溶解产物可通过沉淀(硫酸铵、聚乙烯亚胺)、热处理或类似方法、随后在冷冻干燥前进行脱盐程序(例如超滤、透析及类似方法)而部分纯化。任何细胞制品可通过使用已知交联剂如戊二醛进行交联或固定至固相(例如Eupergit C及类似固相)而得以稳定。

固体反应物(例如酶、盐等)可以以多种不同形式供应到反应，所述形式包括粉末(例如冻干、喷雾干燥及类似干燥)、溶液、乳剂、悬浮液及类似形式。所述反应物可使用对本领域普通技术人员来说已知的方法和装置而容易地冻干或喷雾干燥。例如，蛋白溶液可以以小的等份在-80℃下冷冻，接着将其加入到预冷的冷冻干燥室，随后应用真空。在从样品中去除水后，但在释放真空和回收冻干样品之前，通常将温度升温至4℃保持两小时。

用于还原反应的反应物的量一般根据期望的3，5-二羟基己酸酯的量和伴随所用的酮还原酶底物的量而变化。下述准则可用于确定使用的酮还原酶、辅因子和任选地辅因子再生系统的量。一般来说，5-羟基-3-氧代-己酸酯底物以约20至300克/升的浓度应用，用约50mg至约5g酮还原酶和约10mg至约150mg的辅因子。本领域普通技术人员将容易理解如何改变这些量以使其满足生产能力和生产规模的期望水平。任选的辅因子再生系统的合适量可基于所用的辅因子和/或酮还原酶的量经由常规实验来容易地测定。一般来说，还原剂(例如葡萄糖、甲酸、异丙醇)以高于酮还原酶底物的等摩尔水平的水平利用以基本上实现酮还原酶底物的完全或接近完全的转化。

添加反应物的次序不是关键的。反应物可同时一起添加到溶剂(例如单相溶剂、双相水性共溶剂系统及类似溶剂)，或可选地，一些反应物可单独添加，并且一些反应物可在不同的时间点一起添加。例如，可首先将辅因子再生系统、辅因子、酮还原酶和酮还原酶底物添加到溶剂。

当使用水性共溶剂系统时，为了提高混合效率，则可首先添加并混合辅因子再生系统、酮还原酶和辅因子到水相。然后添加并混合有机相，随后添加酮还原酶底物。可选地，酮还原酶底物可在添加到水相之前于有机相中预混合。

用于进行本文所述的酮还原酶催化还原反应的适合条件包括可通过常规试验容易优化的多种条件，所述常规试验包括但不限于在实验pH和温度下使工程酮还原酶和底物接触然后检测产物(例如使用本文提供的实施例中所述的方法)。

酮还原酶催化的还原通常在范围为约15℃至约75℃的温度下进行。对于某些实施方案，所述反应在范围为约20℃至约55℃的温度下进行。在其他的实施方案中，它在范围为约20℃至约45℃的温度下进行。所述反应还可在室温条件下进行。

一般允许所述还原反应进行，直到获得底物的大致完全或接近完全还原。底物到产物的还原可使用已知方法通过检测底物和/或产物来监控。适合的方法包括气体色谱法、HPLC及类似方法。在反应混合物中产生的3，5-二羟基己酸酯还原产物的转化率一般大于约50％，还可大于约60％，还可大于约70％，还可大于约80％，还可大于90％，并且通常大于约97％。

3，5-二羟基己酸酯还原产物可从反应混合物中回收，并使用本领域技术人员已知的方法来任选地进一步纯化。适合的方法在美国专利6,001,615、6,472,544、6,596,879和6,645,746中描述，所述专利的公开内容通过引用并入本文。另外的适合方法在下述实施例中提供。

如前文论述，5-羟基-3-氧代己酸酯对映体(Ia)的酮还原酶催化的还原在3，5-二羟基己酸酯产物的3-位产生新的立体性碳。还如前文论述，在用本文所述的工程酮还原酶进行的反应中，还原产物以在3-位的高程度的顺式立体选择性产生：因此，使用本文所述的工程酮还原酶产生的3，5-二羟基己酸酯为手性的和非外消旋的。如上所述，本文所述的酮还原酶反应通常产生根据结构式(IIa)的手性的顺式3，5-二羟基己酸酯，它具有至少约99.5％、通常至少约99.9％且代表性地至少约99.95％的非对映体纯度。实施例示例了提供非对映体纯度≥99.993％的6-氰基-(3R，5R)-二羟基己酸叔丁酯的实施方案。

已经发现本文所述的某些底物在临床上重要的降胆固醇他汀药物的合成中特别有用。此类化合物包括其中如本文定义的R¹是低级烃基(在一些实施方案中是叔丁基)、并且X选自氯、氰基和羟基和OR²的那些化合物。因此，根据本文所述的(Ia)、(IIa)、(IIIa)、(IVa)和(Va)结构式的化合物的一些实施方案包括其中R¹是低级烃基或叔丁基和/或X选自氯、氰基和羟基的那些化合物。

在X是-OR⁶，其中R⁶是保护基团的根据(Ia)、(IIa)、(IIIa)、(IVa)和(Va)结构式的化合物的实施方案中，所述基团实际上可以是已知用于在有机合成期间保护羟基的任何保护基团。特定保护基团的特征性将取决于各种合成反应条件，并可被本领域技术人员容易选择用于特定情况。适合的示例性保护基团在Greene & Wuts，“Protective Groups in Organic Synthesis(有机合成中的保护基团)”第3版，1999，John Wiley & Sons，NY(参见例如第17-200页)中描述。在一些实施方案中，所述保护基团选自醚保护基团(例如苄基、叔丁基、四氢吡喃基、甲氧乙氧甲基、甲氧甲基等)、甲硅烷基醚保护基团(例如三甲基甲硅烷基、三乙基甲硅烷基、叔丁基二甲基甲硅烷基、三苯基甲硅烷基等)、酯保护基团(例如苯甲酸酯、烃基化物(alkylate)、卤代烃基化物等)、碳酸酯保护基团(例如烃基甲基(methy)、甲氧甲基、烃基2，2，2，-三氯乙基、烯丙基烯丙基碳酸酯、烃基苄基等)和磺酸酯保护基团(例如磺酸烯丙酯(allylsulfonate)、甲磺酸酯、磺酸苄酯(benzylsulfonate)、甲苯磺酸酯等)。

结构式(Ia)的5-羟基-3-氧代己酸酯对映体可使用本领域众所周知的标准方法来制备。适合的示例性方法在美国专利第6,399,339号(对于其中X＝C1和R¹＝叔丁基的特定实施例，参见实施例1)；美国专利第5,155,251号及在其中引用的各种参考文献(X＝CN、R¹＝叔丁基)、日本专利公布第1723728号(X＝C1、R¹＝叔丁基)和PCT公布WO 2005/018579(X＝C1或CN、R¹＝叔丁基)中描述，所述专利和公布的公开内容通过引用并入本文。图1提供了说明用于以对映体纯的形式和以外消旋混合物来合成底物的示例性方法的图(国际公布第WO 2003/070733和WO 2004/113314号)。

由本文所述的工程酮还原酶催化的还原反应生成的顺式3，5-二羟基己酸酯可用作合成临床上重要的降胆固醇他汀药物如阿托伐他汀、罗苏伐他汀和匹伐他汀的起始物。合成这些他汀类的关键中间体是结构式(IIIa)或(IVa)的受保护的顺式3，5-二羟基己酸酯(见上)。用于合成此类受保护的酯的方法是众所周知的。在结构式(IIIa)化合物中的R²取代基表示未桥接的保护基团的实施方案中，所述保护基团可选自上述的那些保护基团。包括这些保护基团的化合物可按例如Greene & Wuts，“Protective Groups inOrganic Synthesis(有机合成中的保护基团)”第3版，1999，John Wiley &Sons，NY(参见例如第17-200页)中的描述来合成。所用的实际方法将取决于保护基团的特征性。

R²基团合在一起以形成任选地取代的亚烃基桥的实施方案可使用美国专利第5,097,045号(X＝氰基)、美国专利第6,472,544号(X＝卤素或OH)和美国专利第6,344,569号(X＝卤素或CN)中描述的方法从顺式3，5-二羟基己酸酯合成，所述专利的公开内容通过引用并入本文。包括这些保护基团的化合物可按例如Greene & Wuts，“Protective Groups in OrganicSynthesis(有机合成中的保护基团)”第3版，1999，John Wiley & Sons，NY(参见例如第201-245页)中的描述来合成。

作为特定的实例，其中X是氰基的根据结构式(IVa)的化合物可通过用缩醛形成试剂处理对应的(3R，5R)-6-氰基-3，5-二羟基己酸酯来制备，如美国专利第6,344,569号第7栏第30行至第8栏第40行所述，其公开内容通过引用并入本文。

作为另一个特定的实例，其中X是卤素的根据结构式(IVa)的化合物可通过用缩醛形成试剂处理对应的(3R，5S)-6-卤素-3，5-二羟基己酸酯来制备，如美国专利第6,344,569号第9栏第21行至第10栏第34行所述，其公开内容通过引用并入本文。

作为又一个实施例，其中X是氰基的根据结构式(IVa)的化合物可通过用氰化试剂处理所述氯类似物(按上述制备)来制备，如美国专利第6,344,569号第11栏第17行至第12栏第5行所述，其公开内容通过引用并入本文。

在一些实施方案中，受保护的顺式3，5-二羟基己酸酯的R²基团合在一起可形成-BR⁵-的环状硼酸酯保护基团，其中R⁵选自(C1-C12)烃基、(C6-C10)芳基和(C7-C12)芳基烃基。在特定的实施方案中，R⁵是苯基。具有基于环状硼酸酯的保护基团的化合物可按例如Greene & Wuts，“Protective Groupsin Organic Synthesis(有机合成中的保护基团)”第3版，1999，John Wiley &Sons，NY(参见例如第243-245页)中的描述来合成。示例性的苯基硼酸酯保护的顺式3，5-二羟基己酸酯在美国专利第6,867,306号中描述，其通过引用并入本文。

这些和其他反应的示例性实施方案在图2中说明。从(3R，5R)-6-氰基-3，5-二羟基己酸叔丁酯合成(4R，6R)-6-氰甲基-2，2-二甲基-1，3-二噁烷-4-乙酸叔丁酯和从(3R，5S)-6-氯-3，5-二羟基己酸叔丁酯合成(4R，6S)-6-氯甲基-2，2-二甲基-1，3-二噁烷-4-乙酸叔丁酯的特定方法分别在美国专利第6,344,569号的实施例2和3中描述，所述专利的公开内容通过引用并入本文。从(4R，6S)-6-氯甲基-2，2-二甲基-1，3-二噁烷-4-乙酸叔丁酯合成(4R，6R)-6-氰甲基-2，2-二甲基-1，3-二噁烷-4-乙酸叔丁酯的特定方法在美国专利第6,344,569号的实施例3中描述，所述专利的公开内容通过引用并入本文。

结构式(IIa)、(IIIa)、(IVa)和(Va)的受保护的和未受保护的顺式二羟基酯可使用本领域众所周知的方法用于合成降胆固醇他汀类以及包括1，3-顺式二羟基部分的其他有用化合物。例如，使用(3R，5R)-6-氰基-3，5-二羟基己酸叔丁酯合成阿托伐他汀的方法在美国专利第6,596,879号(尤其参见第14栏第22-58行的实施例2)和美国专利第5,097,045号中描述，所述专利的公开内容通过引用并入本文。

使用(3R，5S)-6-氯-3，5-二羟基己酸叔丁酯合成罗苏伐他汀的方法分别在美国专利第5,278,313号和美国专利第6,472,544号中描述，所述专利的公开内容通过引用并入本文。使用(3R，5S，6)-三羟基己酸叔丁酯合成罗苏伐他汀的方法在PCT申请第WO 01/85975号中描述，所述申请的公开内容通过引用并入本文。使用由本文方法所生成的化合物合成其他他汀类对熟练的技术人员来说将是明显的。

7.实施例

本公开内容的各种特征和实施方案在下列代表性实施例中说明，所述实施例旨在说明，而非限制。

在下列描述中，无论哪里使用葡萄糖脱氢酶(GDH)，它均是可从JulichChiral Solutions，Jülich，Germany获得的GDH-CDX901。

7.1实施例1：野生型酮还原酶基因获得和表达载体的构建

编码酿酒酵母酮还原酶的Ydll 24wp基因(Genbank登录号：NP_010159.1；GI：6320079)，根据由所述Ydll 24wp基因编码的酮还原酶(“YDL”)的氨基酸序列(SEQ ID NO：2)进行密码子优化(SEQ ID NO：1)以在大肠杆菌中表达。所述基因使用由42个核苷酸组成的寡核苷酸合成，并被克隆至表达载体pCK110900(如图5所述)的lac启动子的控制下。所述表达载体还包括P15a复制起点和氯霉素抗性基因。所得的质粒使用标准方法转化到大肠杆菌W3110中。选择几个克隆用于测序推定的KRED编码基因。鉴定具有期望的设计序列的基因，并将其用作开发编码工程酮还原酶的基因的起始材料。

此实施例示例了可从中产生编码工程酮还原酶的基因的编码野生型酮还原酶YDL的重组多核苷酸的获得，及适于此类工程的表达载体和宿主细胞。

编码本公开内容的工程酮还原酶的多核苷酸以类似方式克隆至载体pCK110900以在大肠杆菌W3110中表达。

7.2实施例2：酮还原酶粉末的制备；摇瓶程序

将包含具有所感兴趣的酮还原酶基因的质粒的大肠杆菌的单个微生物菌落接种于含有30μg/ml氯霉素和1％葡萄糖的50ml Luria Bertani肉汤。细胞在30℃培养箱中于250rpm振摇生长过夜(至少16小时)。在1升烧瓶中将培养物用250ml极品肉汤(Terrific Broth)(12g/L细菌用胰蛋白胨、24g/L酵母提取物、4ml/L甘油、65mM pH 7.0磷酸钾、1mM MgSO₄、30μg/ml氯霉素)稀释到600nm光学密度(0D₆₀₀)为0.2，并允许其在30℃下生长。当培养物的OD₆₀₀为0.6至0.8时，用1mM IPTG诱导酮还原酶基因的表达，并温育过夜(至少16小时)。通过离心(5000rpm，15分钟，4℃)收集细胞并弃去上清液。细胞沉淀物(pellet)用相等体积冷的(4℃)100mMpH 7.0三乙醇胺(氯化物)缓冲液重悬，并通过如上离心收集。洗涤的细胞在两倍体积冷的三乙醇胺(氯化物)缓冲液中重悬，并以12000psi通过弗氏压碎器两次同时保持在4℃。细胞碎片通过离心(9000rpm，45分钟，4℃)去除。收集澄清的溶解产物上清液并在-20℃下贮藏。冷冻干燥冻结的、澄清的溶解产物提供了粗制酮还原酶的干燥粉末。

此实施例示例了适用于测试酶性质的酮还原酶粉末的生成。

7.3实施例3：6-氰基-(5R)-羟基-3-氧代己酸叔丁酯的制备

将120mL无水四氢呋喃和75mL(540mmol)二异丙胺加至在氮气氛下并浸入-20℃干冰/丙酮浴中的装有添加漏斗(addition funnel)和PTFE包衣的磁性搅拌棒的1L三颈烧瓶。搅拌溶液并冷却至-20℃，然后在45分钟内逐滴加入于己烷中的200mL(500mmol)2.5M正丁基锂，得到浅黄色溶液。另外30分钟后，在25分钟内于搅拌下逐滴加入70mL(520mmol)乙酸叔丁酯，使溶液变得混浊。在-20℃下保持另外1小时后，在35分钟内于搅拌下逐滴加入22.0g 4-氰基-(3R)-羟基丁酸乙酯(≥99.9％e.e，140mmol)在30mL无水四氢呋喃中的溶液，得到浅黄色溶液。将所述溶液在-20℃下保持另外1小时，然后在30分钟内经由导管转移到浸没于冰浴(～5℃)中的搅拌的350mL 1M柠檬酸和250mL甲苯的双相混合物的液面下。在此猝灭过程中，将混合物的温度保持在5-10℃。在结束后，分离相，得到浅黄色有机相(上)和pH～6的橙黄色水相(下)。分离水相，并用250mL甲苯萃取。合并的有机相用100mL 1N HCl洗涤，随后3×100mL蒸馏水洗涤。最后的水洗涤得到pH～5。于60℃在真空下通过旋转蒸发从有机相中去除溶剂，得到31.7g黄色油。

油的¹H-NMR显示6-氰基-(5R)-羟基-3-氧代己酸叔丁酯、3-氧代丁酸叔丁酯和4-氰基-(3R)-羟基丁酸叔丁酯以1.00∶0.27∶0.14摩尔比存在，对应于77％(重量百分比)6-氰基-(5R)-羟基-3-氧代己酸叔丁酯(如果没有其他组分存在)。实际重量百分比可能略微更低，但并未进行更准确地测量。77％(重量百分比)的31.7g油对应于根据4-氰基-3R-羟基丁酸乙酯的77％摩尔收率(理论收率＝31.8g)。

如此和类似制备的粗6-氰基-(5R)-羟基-3-氧代己酸叔丁酯(通常具有范围从60至75％(重量百分比)的纯度，3-氧代丁酸叔丁酯和4-氰基-(3R)-羟基丁酸叔丁酯的平衡)用于下列实施例，除了当指定纯化的底物时之外。用于实施例的6-氰基-(5R)-羟基-3-氧代己酸叔丁酯的指定量是指未对其实际组成作校正的粗制品的量。

7.4实施例4：底物特异性和转化的LC/MS/MS测定

开发了LC/MS/MS方法以分析6-氰基-(5R)-羟基-3-氧代己酸叔丁酯到6-氰基-(3R，5R)-二羟基己酸叔丁酯的转化以及粗底物(实施例4)中3-氧代丁酸叔丁酯到3-羟基丁酸叔丁酯的可能转化：

仪器：Agilent1 100(配有Waters Micromass Quattro Premier LC/MS/MS)

柱：Agilent SB C18(50mm×4.6mm，5μm)

流动相：50％的0.25％(体积百分比)乙酸水溶液，50％乙腈

流速：1.0mL/分钟

背压：60巴

温度：室温

注射：5μL，～0.1mg/ml，于甲醇或其他可水混溶的溶剂中。

保留时间：6-氰基-(3R，5R)-二羟基己酸叔丁酯 1.0分钟

6-氰基-(5R)-羟基-3-氧代己酸叔丁酯 1.3分钟

3-羟基丁酸叔丁酯 1.5分钟

3-氧代丁酸叔丁酯 2.1分钟

离子化/检测：APCI+，使用跃迁MH+＞MH-56(损失叔丁烯)

在0.1mg/ml时，6-氰基-(3R，5R)-二羟基己酸叔丁酯到6-氰基-(5R)-羟基-3-氧代己酸叔丁酯底物的响应比通常为0.84。未对3-氧代丁酸叔丁酯和3-羟基丁酸叔丁酯的MS/MS跃迁进行优化。

7.5实施例5通过LC/MS/MS对6-氰基-3，(5R)-二羟基己酸叔丁酯的非对映体分析

开发了LC/MS/MS方法以分离和分析6-氰基-3，(5R)-二羟基己酸叔丁酯的(3R，5R)和(3S，5R)非对映体。LC条件提供了非对映体的基线分辨率。从0.0001至1.0mg/ml的响应为线性，检测限低于0.0001mg/ml。

仪器：Agilent1 100(配有Waters Micromass Quattro Premier LC/MS/MS)

柱：Agilent SB C8(50mm×4.6mm，5μm)

流动相：等度65％的0.25％乙酸水溶液，35％乙腈

流速：1.0mL/分钟

温度：室温

保留时间：(3S，5R)12.77分钟：(3R，5R)13.67分钟

离子化/检测：APCI+，使用跃迁MH+＞MH-56(损失叔丁烯)

7.6实施例6：通过气体色谱法对(6R)-氰甲基-2，2-二甲基-1，3-二噁烷-4-乙酸叔丁酯的非对映体分析

开发了GC/MS方法以分离和分析(6R)-氰甲基-2，2-二甲基-1，3-二噁烷-4-乙酸酯((6R)-cyanomethyl-2，2-dimethyl-1，3-dioxane-4-acetate)的(4R，6R)和(4S，6R)非对映体：

柱：HP5MS(0.25mm内径，25μm df，30m)

载气：氦，9.44psi，0.7mL/分钟。

烘箱：60℃1分钟，接着15℃/分钟到280℃，然后在280℃保持2分钟

保留时间：(4S，6R)11.44分钟；(4R，6R)11.55分钟

检测：总离子计数

7.7实施例7：6-氰基-3，(5R)-二羟基己酸叔丁酯经由衍生成(6R)-氰甲基-2，2-二甲基-1，3-二噁烷-4-乙酸叔丁酯的非对映体分析

向包含6-氰基-3，(5R)-二羟基己酸叔丁酯的30mg样品加入1mL乙酸乙酯、200μL 2，2-二甲氧基丙烷和20μL甲磺酸。将所述混合物在室温下搅拌20分钟。加入200μL饱和碳酸氢钠水溶液后，上面乙酸乙酯层的样品通过实施例6的方法来分析。

6-氰基-3，(5R)-二羟基己酸叔丁酯的(3R，5R)和(3S，5R)非对映体中的每个都在这些条件下进行了定量衍生。因此，6-氰基-3，(5R)-二羟基己酸叔丁酯的3，(5R)非对映体组分对应于分析的(6R)-氰甲基-2，2-二甲基-1，3-二噁烷-4-乙酸酯衍生物的4，(6R)非对映体组分。

7.8实施例8：评价野生型酮还原酶YDL还原6-氰基-(5R)-羟基-3-氧代己酸叔丁酯的活性

向950μL pH 7.0的100mM三乙醇胺(氯化物)缓冲液、200μL异丙醇、9mg 6-氰基-(5R)-羟基-3-氧代己酸叔丁酯和8mg NAD(P)H的反应混合物中加入包含酮还原酶YDL的15mg酮还原酶粉末。将所述反应混合物在室温下搅拌24小时，然后用1mL乙酸乙酯萃取。离心后，分离有机相并通过旋转蒸发去除溶剂以保留非挥发性油。通过实施例4的方法分析所述非挥发性油的6-氰基-(5R)-羟基-3-氧代己酸叔丁酯以及通过实施例7的方法得到的产物的非对映体组分6-氰基-(3，5R)-二羟基己酸叔丁酯(如果存在)的转化。分析显示了6-氰基-(5R)-羟基-3-氧代己酸叔丁酯的85％转化生成具有＞99％d.e的6-氰基-(3R，5R)-二羟基己酸叔丁酯。

此实施例示例了野生型酮还原酶YDL作为改进5-羟基-3-氧代己酸酯对映体的3-氧代基团还原产生对应的顺式3，5-二羟基己酸酯的性质的工程候选物的鉴定。

7.9实施例9：使用用于辅因子再生的葡萄糖和葡萄糖脱氢酶评价野生型酮还原酶YDL还原6-氰基-(5R)-羟基-3-氧代己酸叔丁酯的活性。

向1mL pH 7.0的100mM三乙醇胺(氯化物)缓冲液、100μL乙酸丁酯、20mg 6-氰基-(5R)-羟基-3-氧代己酸叔丁酯、1mg NAD(P)⁺和35ng葡萄糖的反应混合物加入3mg葡萄糖脱氢酶粉末和包含酮还原酶YDL的20mg酮还原酶粉末。将所述反应混合物在室温下搅拌22小时，然后用1mL乙酸乙酯萃取。离心后，分离有机相并经旋转蒸发去除溶剂以保留非挥发性油。通过实施例4方法分析所述非挥发性油的6-氰基-(5R)-羟基-3-氧代己酸叔丁酯以及通过实施例5方法得到的产物的非对映体组分6-氰基-(3，5R)-二羟基己酸叔丁酯(如果存在)的转化。分析显示了6-氰基-(5R)-羟基-3-氧代己酸叔丁酯的92.6％转化生成具有＞99.9％d.e的6-氰基-(3R，5R)-二羟基己酸叔丁酯。

此实施例示例了当与辅因子再生系统(葡萄糖和葡萄糖脱氢酶)组合使用时野生型酮还原酶YDL的活性和非对映选择性的评价。

7.10实施例10：评价野生型酮还原酶YDL在还原粗6-氰基-(5R)-羟基-3-氧代己酸叔丁酯的反应中的底物和辅因子特异性

野生型酮还原酶YDL粉末对经NADH和NADPH还原(R)-5-羟基-3-氧代己酸叔丁酯和3-氧代丁酸叔丁酯的特异性通过测量反应混合物中340nm下NAD(P)吸光度的增加来评价，所述反应混合物包含在总体积1mL的100mM pH 7.2三乙醇胺(氯化物)缓冲液中的3mg/mL纯化的(R)-5-羟基-3-氧代己酸叔丁酯或～13mM 3-氧代丁酸叔丁酯和0.2-0.3mM NADH或NADPH。

酮还原酶YDL粉末对通过NADPH但不是通过NADH还原(R)-5-羟基-3-氧代己酸叔丁酯具有活性。相对于(R)-5-羟基-3-氧代己酸叔丁酯的活性而言，酮还原酶YDL粉末仅显示通过NADPH还原3-氧代丁酸叔丁酯的非常低的活性。

7.11实施例11：用于对6-氰基-(5R)-羟基-3-氧代己酸叔丁酯的酮还原酶活性的高通量测定

A.高通量NAD(P)H荧光测定：使用

机器人菌落挑取器(Genetix USA，Inc.，Beaverton，OR)将文库菌落挑取到包含180μL LuriaBertani肉汤(LB)、1％葡萄糖和30μg/mL氯霉素(CAM)的96孔浅孔微量滴定板中。于30℃在250rpm振摇下使细胞生长过夜。然后将13μL此培养物转移到包含400μL极品肉汤(TB)和30μg/mL CAM的96深孔板中。于30℃在250rpm振摇下将深孔板温育2.5至3小时(OD₆₀₀ 0.6-0.8)后，细胞培养物的重组基因表达通过终浓度1mM异丙基硫代半乳糖苷(IPTG)诱导。然后于30℃在250rpm振摇下将板温育过夜。

细胞经离心沉淀，在300至400μL裂解缓冲液中重悬并通过在室温下振摇至少2小时而裂解。所述裂解缓冲液包含pH 7.0-7.2的100mM三乙醇胺(氯化物)缓冲液、1mg/mL溶菌酶和500μg/mL多粘菌素B硫酸盐。

通过将测定量的所述裂解混合物转移到包含pH 7-7.2的100mM三乙醇胺(氯化物)缓冲液、0.2-0.3mM NAD(P)H、2至3mg/mL 6-氰基-(5R)-羟基-3-氧代己酸叔丁酯、0至2mg/ml 6-氰基-(3R，5R)-二羟基-己酸叔丁酯、0至600mM葡萄糖和0至600mM葡萄糖酸钠的测定混合物的微量滴定板的孔中，测量酮还原酶活性。反应通过测量在440nm下NAD(P)H的荧光发射的下降作为时间的函数来监控。结果以NAD(P)H的相对荧光单位(RFU)对时间绘制曲线，并且曲线的斜率(RFU/分钟)用于测定反应速率。

B.底物特异性和转化的中等通量LC/MS/MS测定：为确定荧光测定中所测量的NAD(P)H消耗归因于6-氰基-(5R)-羟基-3-氧代-己酸叔丁酯底物到6-氰基-(3R，5R)-二羟基己酸叔丁酯产物的转化或归因于粗底物中的3-氧代丁酸叔丁酯到3-羟基丁酸叔丁酯的还原的程度，将显示所感兴趣的NAD(P)H消耗活性的反应混合物固定到更少的96孔微量滴定板中并用乙酸乙酯萃取。分离的乙酸乙酯提取物用乙腈/水(1/1)稀释，并通过实施例4的LC/MS/MS方法来分析。

7.12实施例12：更稳定的工程酮还原酶的高通量筛选

包括在实施例11A中所制备并鉴定的工程酮还原酶的裂解混合物在范围为37℃至50℃的温度下温育至少16小时。然后在室温下通过实施例4的程序测量温育后在裂解混合物中剩余的酮还原酶活性。温育后剩余的酮还原酶活性与对应的未温育裂解混合物活性的比率(0至1)用作裂解混合物中工程酮还原酶的稳定性的量度。

7.13实施例13：用于6-氰基-(5R)-羟基-3-氧代己酸叔丁酯到6-氰基-(3R，5R)-二羟基己酸叔丁酯的还原的源自野生型YDL的工程酮还原酶的改进活性。

向配置有PTFE包衣的磁性搅拌棒和pH电极(与自动滴定器连接，以根据需要经饲管向容器中pH控制地添加碱)的25mL三颈容器中注入19mL pH 7的100mM三乙醇胺(氯化物)缓冲液、3.0g葡萄糖、包括表2指定量的由表2中的SEQ ID NO.指定的酮还原酶的酮还原酶粉末、13mg葡萄糖脱氢酶粉末、1.0mg NaNADP和最后3g 6-氰基-(5R)-羟基-3-氧代己酸叔丁酯。在22℃下搅拌所述反应混合物。自动滴定器通过添加4N NaOH使pH保持在7，对所述添加进行连续记录。反应进程通过碱的速率和累积添加以及对反应混合物的定期取样(以用实施例4的方法进行提取和分析)来监控。在表2所指定的反应时间后，用两份10mL乙酸乙酯萃取反应混合物两次。将合并的有机提取物通过一薄层硅藻土过滤，并通过在真空下旋转蒸发去除溶剂。通过实施例5的方法对残留的油的非对映体分析显示表2报道的每个此类反应的产物6-氰基-(3R，5R)-二羟基己酸叔丁酯具有＞99.99％的非对映纯度(未检测出其他非对映体)。

表2给出了与酮还原酶粉末对应的SEQ ID NO.、从野生型酮还原酶YDL的氨基酸突变的个数、所用的酮还原酶粉末的量、反应时间以及在该反应时间内达到的6-氰基-(5R)-羟基-3-氧代己酸叔丁酯到6-氰基-(3R，5R)-二羟基己酸叔丁酯的转化。

通过比较表2中的酮还原酶量、反应时间和转化，此实施例示例了与酮还原酶YDL相比，提供改进活性的源自野生型酮还原酶YDL的工程酮还原酶。

7.14实施例14：用于6-氰基-(5R)-羟基-3-氧代己酸叔丁酯到6-氰基-(3R，5R)-二羟基己酸叔丁酯的还原的源自野生型YDL的工程酮还原酶的改进稳定性。

向配置有PTFE包衣的磁性搅拌棒和pH电极(与自动滴定器连接，以根据需要经饲管向容器中pH控制地添加碱)的25mL三颈容器中注入20mL pH 7的100mM三乙醇胺(氯化物)缓冲液、0.5g葡萄糖、表3指定的量的酮还原酶粉末、8mg葡萄糖脱氢酶、2.0mgNaNADP和最后0.3g 6-氰基-(5R)-羟基-3-氧代己酸叔丁酯。在表3指定的温度下搅拌所述反应混合物。自动滴定器通过添加4N NaOH使pH保持在7，对所述添加进行连续记录。反应进程通过碱的速率和累积添加以及对反应混合物的定期取样(以用实施例4的方法进行提取和分析)来监控。在22小时后，用两份10mL乙酸乙酯萃取反应混合物两次。将合并的有机提取物通过一薄层硅藻土过滤，并通过在真空下旋转蒸发去除溶剂。通过实施例5的方法对残留的油的分析显示表3报道的每个此类反应的产物6-氰基-(3R，5R)-二羟基己酸叔丁酯具有＞99.99％非对映纯度(未检测出其他非对映体)。

表3给出了与酮还原酶粉末对应的SEQ ID NO.、从野生型酮还原酶YDL的氨基酸突变的个数、所用的酮还原酶粉末的量、反应温度以及在指定的累积反应时间达到的6-氰基-(5R)-羟基-3-氧代己酸叔丁酯到6-氰基-(3R，5R)-二羟基己酸叔丁酯的转化。

通过比较表3中的酮还原酶量、反应时间和转化，此实施例示例了与YDL相比，提供改进稳定性的源自野生型酮还原酶YDL的工程酮还原酶。尽管在22℃的反应中YDL保留活性并且在22小时反应达到75％的转化，但是在30℃的反应中，YDL在3小时内失去所有活性，仅达到25％的转化。具有氨基酸序列SEQ ID NO.156的工程酮还原酶的稳定性部分得以改进；它在30℃下保留超过3小时，但是在17小时内失去所有活性，达到78％的转化。具有氨基酸序列SEQ ID NO.312的工程酮还原酶在30℃下保留活性超过17小时并且在22小时内达到基本上完全的转化。

7.15实施例15：用于6-氯-(5S)-羟基-3-氧代己酸叔丁酯到6-氯-(3R，5S)-二羟基己酸叔丁酯的还原的源自野生型YDL的工程酮还原酶的改进活性和非对映选择性。

向配置有PTFE包衣的磁性搅拌棒和pH电极(与自动滴定器连接，以根据需要经饲管向容器中pH控制地添加碱)的50mL三颈容器中注入21mL pH 7的100mM三乙醇胺(氯化物)缓冲液、0.5g葡萄糖、含有包含由表4中的SEQ ID NO.指定的酮还原酶的10mg酮还原酶粉末的2mL相同缓冲液、10mg葡萄糖脱氢酶粉末、2.0mg NAD或NaNADP、和最后0.3g 6-氯-(5S)-羟基-3-氧代己酸叔丁酯。在22℃下搅拌所述反应混合物。自动滴定器通过添加4N NaOH使pH保持在6.9，对所述添加进行连续记录。反应进程通过碱的速率和累积添加以及对反应混合物的定期取样(用实施例4的方法进行提取和分析)来监控。在表4指定的反应时间后，用两份10mL乙酸乙酯萃取反应混合物两次。将合并的有机提取液通过硅藻土过滤，并通过在真空下旋转蒸发去除溶剂以得到0.2g残留的油。

残留油中的6-氯-(3R，5S)-二羟基己酸叔丁酯产物的非对映纯度通过实施例7的方法来确定。(3R，5S)-二醇是顺式非对映体(用于标记5-位R或S的惯例在6-氰甲基和6-氯甲基之间颠倒)。

表4给出了与酮还原酶粉末对应的SEQ ID NO.、从野生型酮还原酶YDL的氨基酸突变的个数、所用的酮还原酶粉末的量、所用的辅因子、反应时间、6-氯-(5S)-羟基-3-氧代己酸叔丁酯的转化以及6-氯-(3R，5S)-二羟基己酸叔丁酯产物的非对映纯度。

此实施例示例了与酮还原酶YDL相比提供改进活性和改进非对映选择性的源自野生型酮还原酶YDL的工程酮还原酶以及此类工程酮还原酶用于制备6-氯-(3R，5S)-二羟基己酸叔丁酯的用途。

7.16实施例16：使用用于辅因子再生的异丙醇和仲醇脱氢酶通过工程酮还原酶的6-氰基-(5R)-羟基-3-氧代己酸叔丁酯到6-氰基-(3R，5R)-二羟基己酸叔丁酯的还原。

向包含2mM MgSO₄的2mL pH 7.2的100mM三乙醇胺(氯化物)缓冲液、360mg 6-氰基-(5R)-羟基-3-氧代己酸叔丁酯和200μL异丙醇的反应混合物中加入包含具有SEQ ID NO.330的氨基酸序列的工程酮还原酶的30mg酮还原酶粉末、包含源自ADH-LK且具有使异丙醇氧化成丙酮的活性的工程仲醇脱氢酶的仲醇脱氢酶粉末以及5mg NaNADP。在室温下将所述反应混合物搅拌1小时，然后用1mL乙酸乙酯萃取。离心后，分离有机相并通过旋转蒸发去除溶剂以保留非挥发性油。通过实施例4和7的方法分析非挥发性油。6-氰基-(5R)-羟基-3-氧代己酸叔丁酯被100％转化成具有＞99.9％d.e(＝＞99.95％非对映选择性)的6-氰基-(3R，5R)-二羟基己酸叔丁酯。

此实施例示例了使用与包含仲醇(异丙醇)和仲醇脱氢酶的辅因子再生系统组合的工程酮还原酶还原5-羟基-3-氧代己酸酯的对映体的3-氧代基团产生对应的顺式3，5-二羟基己酸酯。

7.17实施例17：6-氰基-(3R，5R)-二羟基己酸叔丁酯(结构式IIa的化合物)的制备。

向配置有PTFE包衣的磁性搅拌棒和pH电极(与自动滴定器连接，以根据需要经饲管向烧瓶中pH控制地添加碱)的100mL三颈烧瓶中注入19mL pH 7的100mM三乙醇胺(氯化物)缓冲液、8.68g葡萄糖、包含具有氨基酸序列SEQ ID NO.316的工程酮还原酶的100mg酮还原酶粉末、40mg葡萄糖脱氢酶粉末、6mg NaNADP和最后12g 6-氰基-(5R)-羟基-3-氧代己酸叔丁酯。在22℃下搅拌所述反应混合物。自动滴定器通过添加4N NaOH使pH保持在6.9，对所述添加进行连续记录。在22小时后，消耗了8.9ml4N NaOH，并且通过实施例4的方法分析的样品提取物显示了＞99％的转化。将反应混合物通过硅藻土过滤，并经由硅藻土加入20mL乙酸乙酯。分离水相，并用20mL乙酸乙酯萃取。通过在真空下旋转蒸发从合并的有机提取物中去除溶剂，以获得9.80g粗6-氰基-(3R，5R)-二羟基己酸叔丁酯的油。

此实施例示例了通过本发明方法使用工程酮还原酶制备和回收顺式3，5-二羟基己酸酯。

7.18实施例18：(6R)-氰甲基-2，2-二甲基-1，3-二噁烷-(4R)-乙酸叔丁酯(结构式IVa的化合物)的制备。

向于实施例17中获得的9.80粗6-氰基-(3R，5R)-二羟基己酸叔丁酯加入26mL 2，2-二甲氧基丙烷和260μL甲磺酸。在22℃下将所述反应混合物搅拌2小时。加入25mL 5％(半饱和)碳酸氢钠水溶液后，水相的pH为7.5。用52mL庚烷萃取混合物，并用25mL 5％碳酸氢钠水溶液萃取分离的有机相。通过在真空下旋转蒸发从有机相中去除溶剂。在温和加热(～45℃)下将残留物溶于70mL庚烷，冷却并在室温下保持30分钟，然后冷却，保持在0℃以完成结晶。过滤和干燥获得8.1g为微黄色固体的(6R)-氰甲基-2，2-二甲基-1，3-二噁烷-(4R)-乙酸叔丁酯。通过实施例6方法的分析显示了97.8％(面积比)的纯度并且无可检测的(4S，6R)非对映体。

此实施例示例了从通过本发明方法制备的顺式3，5-二羟基己酸酯来制备和回收受保护的顺式二羟基己酸酯。

7.19实施例19：6-氰基-(3R，5R)-二羟基己酸叔丁酯的制备。

向配置有PTFE包衣的磁性搅拌棒、添加漏斗和pH电极(与自动滴定器连接，以根据需要经饲管向烧瓶中pH控制地添加碱)的加套3L三颈烧瓶注入6.36g三乙醇胺和427mL水。通过加入3,85g浓盐酸将溶液的pH调整至6.9。加入195g D-葡萄糖、0.90g葡萄糖脱氢酶粉末、包含具有氨基酸序列SEQ ID NO.316的工程酮还原酶的2.25g酮还原酶粉末以及0.135NaNADP。在22℃的搅拌并且自动滴定器准备根据需要提供4NNaOH下，从添加漏斗中加入270g 6-氰基-(5R)-羟基-3-氧代己酸叔丁酯。自动滴定器通过添加4N NaOH使pH保持在6.9，对所述添加进行连续记录。在22小时后，消耗196.7ml 4N NaOH，并且通过实施例4的方法分析的样品提取物显示了＞99％的转化。加入450mL乙酸乙酯并将混合物通过硅藻土过滤。分离水相并用450mL乙酸乙酯萃取。通过在真空下旋转蒸发从合并的有机提取物中去除溶剂，以获得232g粗6-氰基-(3R，5R)-二羟基己酸叔丁酯的油。

此实施例示例了通过本发明的方法使用工程酮还原酶更大规模地制备和回收顺式3，5-二羟基己酸酯。

7.20实施例20：6-氰基-(5S)-羟基-3-氧代己酸叔丁酯的还原。

根据与实施例3中所述的4-氰基-(3S)-羟基丁酸乙酯的R-对映体的制备类似的程序，由4-氰基-(3S)-羟基丁酸乙酯(98％e.e.)制备6-氰基-5-羟基-3-氧代己酸叔丁酯的S-对映体。

向配置有PTFE包衣的磁性搅拌棒和pH电极(与自动滴定器连接，以根据需要经饲管向容器中pH控制地添加碱)的25mL三颈容器中注入20mL pH 7的100mM三乙醇胺(氯化物)缓冲液、1.80g葡萄糖、9mg葡萄糖脱氢酶粉末、包含具有氨基酸序列SEQ ID NO.316的工程酮还原酶的30mg酮还原酶粉末、2.5mg NaNADP和最后3g 6-氰基-(5S)-羟基-3-氧代己酸叔丁酯。在22℃下搅拌所述反应混合物。自动滴定器通过添加4NNaOH使pH保持在7，对所述添加进行连续记录。反应进程通过碱的速率和累积添加以及对反应混合物的定期取样(用实施例4的方法进行提取和分析)来监控。在38小时后，转化为47％。用10mL乙酸乙酯萃取反应物两次。将合并的有机提取物通过硅藻土过滤，并通过在真空下旋转蒸发去除溶剂以保留油。

粗6-氰甲基-2，2-二甲基-1，3-二噁烷-4-乙酸叔丁酯从所述油(实施例7)中获得并通过实施例6的方法来分析，显示了95.3％d.e的(4R，6S)非对映体，对应于还原反应的二醇产物的((3R，5S)非对映体。(注：(4R，6S)非对映体具有与其(4S，6R)对映体相同的保留时间并且(4S，6S)非对映体具有与其(4R，6R)对映体相同的保留时间)。

当此实施例的工程酮还原酶用于还原6-氰基-5-羟基-3-氧代己酸叔丁酯的R对映体时，它以基本上完全的非对映选择性提供了顺式(3R，5R)二醇(参见实施例13、14以及图6和图7)。此实施例示例了当用于还原6-氰基-5-羟基-3-氧代己酸叔丁酯的5S-对映体时，它还具有3R选择性。

7.21实施例21：6-氰基-5-羟基-3-氧代己酸叔丁酯的对映体的97％5R、3％5S混合物的还原(94％e.e.)。

此程序与前述实施例相同，除了将2.91g 6-氰基-(5R)-羟基-3-氧代己酸叔丁酯和0.09g 6-氰基-(5S)-羟基-3-氧代己酸叔丁酯加入反应。反应在20小时时达到97％的转化，此后如在前述实施例中所述回收产物油。

粗(4，6)-6-氰甲基-2，2-二甲基-1，3-二噁烷-4-乙酸叔丁酯从所述油(实施例7)中获得并通过实施例6的方法经GC/MS来分析，显示了99.73％的(4R，6R)非对映体(对应于二醇的顺式-(3R，5R)非对映体)和0.27％的(4R，6S)非对映体(对应于二醇的(3R，5S)非对映体)的混合物(即99.46％d.e.)。

与前述实施例组合，此实施例示例了对还原6-氰基-5-羟基-3-氧代己酸叔丁酯的R-对映体比S-对映体具有立体特异性的工程酮还原酶。(3R，5)-二醇的5-位(和由其汀生的(4R，6)-二噁烷的6-位)的立体纯度与5-羟基-3-氧代己酸酯底物的立体纯度相比有了实质性提升(99.46％d.e对94％e.e.)。工程酮还原酶与少于十分之一的加入到反应中的3％S-底物反应，而与基本上所有的97％R-底物反应。因此，当5-羟基-3-氧代己酸酯底物具有较低立体纯度时，本公开内容的工程酮还原酶可在顺式-3，5-二羟基己酸酯产物中提供更高程度的立体纯度。进一步地，当从3-羟基丁酸酯制备5-羟基-3-氧代己酸酯底物(如在实施例3中示例)时，可从较低立体纯度的3-羟基丁酸酯中净获得顺式-3，5-二羟基己酸酯产物的更高程度的立体纯度。

7.22实施例22：由本发明方法制备的6-氰基-(3R，5R)-二羟基己酸叔丁酯的非对映纯度

通过实施例17的方法制备粗6-氰基-(3R，5R)-二羟基己酸叔丁酯的油。将所述油样品以1.0mg/mL用于水中的9％乙腈溶解，并通过实施例5的LC/MS/MS方法来分析。色谱图以放大的刻度示于图6(上栏)。没有检测出高于0.005％的6-氰基-(3R，5R)-二羟基己酸叔丁酯的非对映体。

为了比较，6-氰基-(3R，5R)-二羟基己酸叔丁酯的溶液由得自商业来源(Aldrich目录#53,901-5)的结晶(6R)-(2-氰乙基)-2，2-二甲基-1，3-二噁烷-(4R)-乙酸叔丁酯制备，所述结晶包含0.1％(4S，6R)非对映体(通过实施例6的方法来分析；参见实施例23)。将250mg商品化(6R)-(2-氰乙基)-2，2-二甲基-1，3-二噁烷-(4R)-乙酸叔丁酯悬浮于包含2001N HCl的2mL 1∶1甲醇：水中。将所述混合物在室温下搅拌16小时。加入500μL饱和的碳酸氢钠水溶液和5mL乙酸乙酯。分离有机相并通过在真空下旋转蒸发去除溶剂以得到187mg为微黄色油的6-氰基-(3R，5R)-二羟基-己酸叔丁酯。

将这种油的样品以1.0mg/mL用于水中的9％乙腈溶解并也通过实施例5的LC/MS/MS方法来分析。色谱图以放大的刻度示于图6(下栏)。该色谱图显示得自商品化(6R)-(2-氰乙基)-2，2-二甲基-1，3-二噁烷-(4R)-乙酸叔丁酯中0.1％的(4S，6R)非对映体的6-氰基-3，5-二羟基己酸叔丁酯的0.1％(3S，5R)非对映体的峰。

通过比较图6的上色谱图和下色谱图，此实施例示例了提供大致非对映体纯的顺式3，5-二羟基己酸酯化合物的本发明工艺。

7.23实施例23：通过本发明方法制备的未结晶的(6R)-(2-氰乙基)-2，2-二甲基-1，3-二噁烷-(4R)-乙酸叔丁酯的非对映纯度。

将由实施例3中＞99.9％e.e.的4-氰基-(3R)-羟基丁酸乙酯制备的粗6-氰基-(5R)-羟基-3-氧代己酸叔丁酯转化成(6R)-(2-氰乙基)-2，2-二甲基-1，3-二噁烷-(4R)-乙酸叔丁酯，后者在结晶前通过GC/MS分析非对映纯度。

向配置有PTFE包衣的磁性搅拌棒和pH电极(与自动滴定器连接，以根据需要经饲管向烧瓶中pH控制地添加碱)的100mL三颈烧瓶中注入18mL pH 7.0的100mM三乙醇胺(氯化物)缓冲液、12g粗6-氰基-(5R)-羟基-3-氧代己酸叔丁酯和7.99g葡萄糖。将溶液的pH用0.26mL 4NNaOH重新调整至7.0。加入包括含有具有氨基酸序列SEQ ID NO.316的工程酮还原酶的200mg酮还原酶粉末、15mg葡萄糖脱氢酶粉末和5mg NaNADP的1mL相同缓冲液，并在22℃下搅拌所述反应混合物。自动滴定器通过添加4N NaOH使pH保持在6.9，对所述添加进行连续记录。在4.6小时后加入另外15mg葡萄糖脱氢酶粉末和1g葡萄糖，并且在7小时后加入另外15mg葡萄糖脱氢酶粉末和1.5mg NaNADP。总共12小时后，消耗了9.04ml 4N NaOH，通过实施例4的方法分析的样品提取物显示了99.3％的转化。将2.5g硅藻土加至反应混合物中，然后用50mL乙酸乙酯萃取反应混合物三次。通过在真空下旋转蒸发从合并的有机提取物中去除溶剂以获得10.40g粗6-氰基-(3R，5R)-二羟基己酸叔丁酯的油。

向所述粗6-氰基-(3R，5R)-二羟基己酸叔丁酯加入22mL 2，2-二甲氧基丙烷和100μL甲磺酸。在室温下搅拌混合物2小时。在添加5mL饱和碳酸氢钠水溶液后，水相的pH为8.0。用60mL己烷萃取所述混合物，并通过在真空下旋转蒸发从提取物中去除溶剂以获得包括(6R)-(2-氰乙基)-2，2-二甲基-1，3-二噁烷-(4R)-乙酸叔丁酯的金色油。

将所述油的样品以5mg/mL溶解于乙酸乙酯，通过下述GC/MS方法对其进行分析：

柱：HP5MS(0.25mm内径，25μm df，30m)

载气：氦，9.44psi，0.7mL/分钟

烘箱：50℃1分钟，接着30℃/分钟到220℃，然后在220℃保持3分钟

保留时间：(4S，6R)7.9分钟；(4R，6R)8.0分钟

检测：单离子监控，m/z 198。

GC/MS分析显示了(6R)-(2-氰乙基)-2，2-二甲基-1，3-二噁烷-(4R)-乙酸叔丁酯油是大致非对映体纯的。为了比较，将商业上获得的(Aldrich，目录号53,901-5)样品即结晶(6R)-(2-氰乙基)-2，2-二甲基-1，3-二噁烷-(4R)-乙酸叔丁酯以5mg/mL溶解于乙酸乙酯，并同样地分析，显示了0.10％的(4S，6R)非对映体。图7显示了所述油和所述结晶(6R)-(2-氰乙基)-2，2-二甲基-1，3-二噁烷-(4R)-乙酸叔丁酯的重叠GC/MS色谱图。

然后将所述油溶解于17mL 50℃的己烷，并将溶液冷却至0℃以结晶。过滤和空气干燥获得98.7％(面积比)化学纯度的8.1g结晶(6R)-(2-氰乙基)-2，2-二甲基-1，3-二噁烷-(4R)-乙酸叔丁酯。

此实施例示例了提供大致非对映体纯的受保护的顺式3，5-二羟基己酸酯化合物而不需任何非对映体纯化(例如通过结晶)的本发明工艺。

7.24实施例24：(6R)-(2-氨乙基)-2，2-二甲基-1，3-二噁烷-(4R)-乙酸叔丁酯(式V)的制备。

使用美国专利第5,003,080号第49栏第16-43行中公开的方法将如在实施例18和23中制备的(6R)-(2-氰乙基)-2，2-二甲基-1，3-二噁烷-(4R)-乙酸叔丁酯转化成标题化合物，所述专利通过引用并入本文。具体地说，在50psi和40℃下在振荡器中用0.5g兰尼镍#30和氢气处理于100mL用气态氨饱和的甲醇中的5.63g(0.048mol)(6R)-(2-氰乙基)-2，2-二甲基-1，3-二噁烷-(4R)-乙酸叔丁酯的溶液。16小时后，薄层色谱法表明没有起始腈存在。将悬浮液冷却，通过助滤剂过滤并浓缩成油。此粗油通过硅胶快速色谱法(用30∶20∶1(乙酸乙酯∶甲醇∶氢氧化铵)作为洗脱剂)纯化以得到4.93g标题化合物：式V(98.2％(面积比))的(6R)-(2-氨乙基)-2，2-二甲基-1，3-二噁烷-(4R)-乙酸叔丁酯的澄清的油，其具有可接受的IR、NMR、C-NMR和MS谱。

7.25实施例25：(6R)-[2[2-(氟苯基)-5-(-(1-甲基乙基)-3-苯基-4-[(苯氨基)羰基]-1H-吡咯-1-基]乙基]-2，2-二甲基-1，3-二噁烷-(4R)-乙酸叔丁酯(式VI)的制备。

使用美国专利第5,003,080号第49栏第43-60行中公开的方法将如在实施例24中制备的(6R)-(2-氨乙基)-2，2-二甲基-1，3-二噁烷-(4R)-乙酸叔丁酯转化成标题化合物，所述专利通过引用并入本文。具体地说，将于50mL庚烷∶甲苯(9∶1)中的1.36％(4.97mol)(6R)-(2-氨乙基)-2，2-二甲基-1，3-二噁烷-(4R)-乙酸叔丁酯(式IV)和1.60g(3.83mol)(±)-4-氟-α-[2-甲基-1-氧代丙基]-γ-氧代-N，β-二苯基苯丁酰胺(为[R-(R’，R’)]、[R-(R’，S’)]、[S-(R’，R’)]和[S-R’，S’)]异构体的混合物)(式V)的溶液在回流下加热24小时。将溶液轻微冷却并加入15mL 2-丙醇。使混合物冷却至25℃并过滤以得到1.86标题化合物：式VI的(6R)-[2[2-(氟苯基)-5-(-(1-甲基乙基)-3-苯基-4-[(苯氨基)羰基]-1H-吡咯-1-基]乙基]-2，2-二甲基-1，3-二噁烷-(4R)-乙酸叔丁酯的黄色固体，其具有可接受的NMR光谱。

7.26实施例26：(2R-反式)-5-(4-氟苯基)-2-(1-甲基乙基)-N，4-二苯基-1-[2-(四氢-4-羟基-6-氧代-2H-吡喃-2-基)乙基]-1H-吡咯-3-甲酰胺(也称为阿托伐他汀内酯)(式VII)的制备。

使用美国专利第5,003,080号第50栏第4-30行中公开的方法将如在实施例25中制备的(6R)-[2[2-(氟苯基)-5-(-(1-甲基乙基)-3-苯基-4-[(苯氨基)-羰基]-1H-吡咯-1-基]乙基]-2，2-二甲基-1，3-二噁烷-(4R)-乙酸叔丁酯转化成标题化合物，所述专利通过引用并入本文。具体地说，将4.37g(6.68mol)的(6R)-[2[2-(氟苯基)-5-(-(1-甲基乙基)-3-苯基-4-[(苯氨基)羰基]-1H-吡咯-1-基]乙基]-2，2-二甲基-1，3-二噁烷-(4R)-乙酸叔丁酯溶解于200mL四氢呋喃并加入15mL 10％盐酸溶液，将溶液搅拌15小时。向此溶液中加入氢氧化钠(3.6g)并将混合物搅拌30小时。通过添加150mL水、90mL己烷并分离层来终止反应。用稀盐酸溶液酸化水层，搅拌3小时并用150mL乙酸乙酯萃取。将1滴浓盐酸加至乙酸乙酯溶液中并使溶液静置18小时。真空浓缩所述溶液，将浓缩液再溶解于50mL乙酸乙酯中并用1滴浓盐酸处理。将溶液搅拌2小时，真空浓缩并溶解于3.0mL甲苯中。分两批分离标题化合物，即式VII的(2R-反式-5-(4-氟苯基)-2-(1-甲基-乙基)-N，4-二苯基-1-[2-(四氢-4-羟基-6-氧代-2H-吡喃-2-基)乙基]-1H-吡咯-3-甲酰胺(3.01g)，其也称为阿托伐他汀内酯。

7.27实施例27：式VIII的[R-(R^*，R^*)]-2-(4-氟苯基)-β-δ-二羟基-5-(1-甲基乙基)-3-苯基-4-[(苯氨基)羰基]-1H-吡咯-1-庚酸钙盐(2∶1)的制备。

使用1999年10月19日公布的标题为“Crystalline[R-(R^*，R^*)]-2-(4-fluorophenyl)-β，δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid hemi calcium salt(atorvastatin)”(结晶[R-(R^*，R^*)]-2-(4-氟苯基)-β，δ-二羟基-5-(1-甲基乙基)-3-苯基-4-[(苯氨基)羰基]-1H-吡咯-1-庚酸半钙盐(阿托伐他汀))的美国专利5,969,156的实施例1A或1B中公开的方法将如在实施例26中制备的(2R-反式)-5-(4-氟苯基)-2-(1-甲基乙基)-N，4-二苯基-1-[2-(四氢-4-羟基-6-氧代-2H-吡喃-2-基)乙基]-1H-吡咯-3-甲酰胺转化成式VIII的标题化合物，所述专利的实施例通过引用并入本文。标题化合物以通用名称阿托伐他汀半钙盐和商标名称

而众所周知。从实施例31的内酯制备所述钙盐在美国专利5,273,995的实施例10中公开，所述专利通过引用并入本文。

i.钠盐

具体地说，将来自实施例20的1摩尔内酯(540.6g)溶解于5L甲醇中。溶解后，加入1L H₂O。在搅拌的同时，加入0.98当量NaOH并且通过HPLC进行反应直到剩余2％或更少的二醇酸的内酯和甲酯。不使用过量的NaOH，因为在随后的步骤中添加CaCl₂时可形成Ca(OH)₂。水解内酯，即可形成[R-(R^*，R^*)]-2-(4-氟苯基)-β-δ-二羟基-5-(1-甲基乙基)-3-苯基-4-[(苯氨基)羰基]-1H-吡咯-1-庚酸钠盐(阿托伐他汀钠盐)。

ii.钙盐

在水解完成后，加入10L H₂O，然后用EtOAc/己烷的1∶1混合物洗涤至少两次。每次洗涤应包含10L各自的EtOAc/己烷。如果钠盐是纯的，则加入15L甲醇。如果它不纯和/或含有颜色，则加入100g G-60活性炭，搅拌2小时，通过supercel过滤，然后用15LMeOH洗涤。通过HPLC对反应混合物进行重量/体积％以确定甲醇水溶液中阿托伐他汀钠盐的精确量。

将1当量或略过量的CaCl₂·2H₂0(73.5g)溶解于20L H₂O中。将CaCl₂溶液和所述甲醇水溶液都加热至60℃。在强烈搅拌下将CaCl₂溶液缓慢地加至60℃阿托伐他汀钠盐的甲醇水溶液。在添加结束后，将混合物缓慢冷却至15℃并过滤沉淀的式VIII的钙盐。用5L H₂O洗涤滤饼。在真空烘箱中于50℃下干燥。

得自干燥滤饼的钙盐可通过溶解于4L EtOAc(50℃)而再结晶，通过

过滤，用1L EtOAc(50℃)洗涤滤液，然后将3L非极性溶剂如己烷加至50℃EtOAc溶液中。然后将所得的式VIII晶体空气干燥或加热干燥。

7.28实施例28：酮还原酶的制备；发酵程序。

在15L充气式搅拌发酵罐中，将包含0.88g/L硫酸铵、0.98g/L柠檬酸钠；12.5g/L三水磷酸氢二钾、6.25g/L磷酸二氢钾、6.2g/L Tastone-154酵母提取物、0.083g/L柠檬酸铁铵以及8.3ml/L痕量元素溶液(含有2g/L二水氯化钙、2.2g/L七水硫酸锌、0.5g/L一水硫酸锰、1g/L七水硫酸亚铜、0.1g/L四水钼酸铵和0.02g/L十水四硼酸钠)的6.0L生长培养基加热至30℃的温度。向所述发酵罐接种大肠杆菌W3110(包含具有所感兴趣的酮还原酶基因的质粒)的指数末期培养物，其如实施例3中所述在摇瓶中生长到0.5至2.0的起始OD₆₀₀。以500-1500rpm搅动发酵罐，并且以1.0-15.0L/分钟向所述发酵容器提供空气以保持30％饱和或更多的溶氧水平。通过添加20％v/v氢氧化铵将培养物的pH控制在7.0。通过添加包含500g/L工业葡萄糖、12g/L氯化铵和10.4g/L七水硫酸镁的料液(feed solution)维持培养物的生长。在培养物达到50的OD₆₀₀后，通过添加异丙基-b-D-硫代半乳糖苷(IPTG)到1mM的终浓度来诱导酮还原酶的表达。使培养物生长另外的14小时。然后将培养物冷却至4℃并保持在4℃直到收集。通过在Sorval RC 12BP离心机中于4℃下以5000G离心40分钟收集细胞。收集的细胞直接用于下述下游回收工艺或在4℃下贮藏直到这种使用。

在4℃下将细胞沉淀物重悬于2倍体积pH 6.8的100mM三乙醇胺(氯化物)缓冲液(每体积的湿细胞糊状物(wet cell paste))。通过使用12000psig的压力将悬浮液通过设有二级匀浆阀部件(assembly)的匀浆器，从细胞中释放细胞内酮还原酶。破裂后立即将细胞匀浆物冷却至4℃。向溶解产物中加入pH 7.2的10％w/v聚乙烯亚胺溶液至0.5％w/v的终浓度，并搅拌30分钟。所得的悬浮液通过在标准的实验室离心机中以5000G离心30分钟而澄清。滗出澄清的上清液并使用截留分子量为30Kd的纤维素超滤膜浓缩10倍。将终浓缩物分散于浅器皿中，在-20℃下冷冻，并且冻干成粉末。酮还原酶粉末在-80℃下贮藏。

此实施例示例了通过可调整至实用规模的程序(practical scaleableprocedure)制备酮还原酶粉末。

本申请中引用的所有出版物、专利、专利申请和其他文献为了所有目的特此通过引用以其整体并入，达到如同单独地表明每一个单独的出版物、专利、专利申请或其他文献为了所有目的通过引用并入的相同程度。

尽管已经示例并描述了各种特定实施方案，但是应理解，可作出各种改变而不偏离本发明的精神和范围。

序列表

<110>洛林.琼.吉尔

利萨.玛丽.纽曼

艾米丽.穆德弗

吉伽特.W.哈思曼

史提芬尼.J.珍妮

朱军

贝娜.贝洛茨安

约翰.H.格瑞特

詹姆士.拉伦德

<120>用于制备立体异构纯的他汀类及其合成中间体的组合物和方法

<130>376247-012WO

<140>PCT/US2007/080125

<141>2007-10-01

<150>US 60/848,951

<151>2006 10 02

<160>366

<210>1

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>1

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacacg ttggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcgca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacat caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>2

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>2

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Arg Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Ala

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Ile Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>3

<211>762

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>3

atgtctaacc gtctggatgg caaagtagcc atcattaccg gcgggactct gggtatcggt 60

ttggcaatcg ccacgaaatt tgtagaggag ggtgcgaaag taatgattac tggtcgtcac 120

tccgatgtag gtgaaaaggc cgccaaatca gtaggcactc cggatcagat tcagtttttt 180

cagcacgatt catccgatga agatggctgg acgaaactgt tcgacgccac cgagaaagca 240

ttcggcccgg ttagcacctt agtgaacaat gcagggattg cagttaacaa aagcgttgaa 300

gaaactacca cggccgaatg gcgtaaactg ctggccgtta atctggatgg tgtttttttc 360

ggcacccgtc tgggcattca gcgcatgaaa aataaaggct tgggcgctag catcatcaat 420

atgagcagta ttgaggggtt cgtaggcgat ccgagcctgg gggcatacaa cgcttccaag 480

ggggcggtac gtatcatgtc gaaaagcgca gcgctggatt gcgcactgaa ggactacgat 540

gtgcgtgtca acacagtaca tccgggctat atcaagaccc cgctggtcga tgatctgccg 600

ggtgctgagg aagcgatgtc acagcgtacg aaaaccccta tgggccacat tggcgaaccg 660

aatgacatcg catatatctg tgtgtacctg gcatctaatg aatcgaaatt tgcgacgggt 720

tccgaatttg tggtcgacgg cgggtatacc gcacagtaat ga 762

<210>4

<211>253

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>4

Met Ser Asn Arg Leu Asp Gly Lys Val Ala Ile Ile Thr Gly Gly Thr

1 5 10 15

Leu Gly Ile Gly Leu Ala Ile Ala Thr Lys Phe Val Glu Glu Gly Ala

20 25 30

Lys Val Met Ile Thr Gly Arg His Ser Asp Val Gly Glu Lys Ala Ala

35 40 45

Lys Ser Val Gly Thr Pro Asp Gln Ile Gln Phe Phe Gln His Asp Ser

50 55 60

Ser Asp Glu Asp Gly Trp Thr Lys Leu Phe Asp Ala Thr Glu Lys Ala

65 70 75 80

Phe Gly Pro Val Ser Thr Leu Val Asn Asn Ala Gly Ile Ala Val Asn

85 90 95

Lys Ser Val Glu Glu Thr Thr Thr Ala Glu Trp Arg Lys Leu Leu Ala

100 105 110

Val Asn Leu Asp Gly Val Phe Phe Gly Thr Arg Leu Gly Ile Gln Arg

115 120 125

Met Lys Asn Lys Gly Leu Gly Ala Ser Ile Ile Asn Met Ser Ser Ile

130 135 140

Glu Gly Phe Val Gly Asp Pro Ser Leu Gly Ala Tyr Asn Ala Ser Lys

145 150 155 160

Gly Ala Val Arg Ile Met Ser Lys Ser Ala Ala Leu Asp Cys Ala Leu

165 170 175

Lys Asp Tyr Asp Val Arg Val Asn Thr Val His Pro Gly Tyr Ile Lys

180 185 190

Thr Pro Leu Val Asp Asp Leu Pro Gly Ala Glu Glu Ala Met Ser Gln

195 200 205

Arg Thr Lys Thr Pro Met Gly His Ile Gly Glu Pro Asn Asp Ile Ala

210 215 220

Tyr Ile Cys Val Tyr Leu Ala Ser Asn Glu Ser Lys Phe Ala Thr Gly

225 230 235 240

Ser Glu Phe Val Val Asp Gly Gly Tyr Thr Ala Gln

245 250

<210>5

<211>1050

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>5

atgaaagcca ttcagtacac tcgtatcggt gcggaaccag aactgactga aatcccgaag 60

ccggaaccgg gcccgggcga agtactgctg gaagtcacgg cagctggcgt gtgccattcc 120

gatgatttca ttatgtctct gccggaagaa cagtacacct acggcctgcc gctgaccctg 180

ggtcatgaag gtgctggtaa agttgccgca gttggcgaag gtgttgaagg gttggatatt 240

ggcaccaatg tggttgtgta cggcccatgg ggttgtggca actgttggca ttgcagtcag 300

ggcctggaga actattgctc ccgtgcgcag gaactgggta ttaacccgcc tggtctgggt 360

gctccggggg ctttggcaga atttatgatt gtcgactcac cacgtcattt ggtcccgatt 420

ggcgatttag accctgttaa aactgttccg ttgactgatg cgggcctgac cccataccat 480

gcaatcaaac gctccctgcc gaaactgcgc ggcggctctt atgcagtagt gatcggtacg 540

ggtggcctgg gccacgtggc tatccaactg ctgcgtcatt tatctgctgc aacggtgatc 600

gccttggacg tttctgccga taaactggaa ctggctacca aagtcggcgc acatgaagta 660

gtcctgtctg ataaagatgc agcggagaat gtgcgtaaaa ttactggtag ccaaggtgca 720

gctttggtgt tggattttgt gggctatcag cctaccattg acaccgccat ggcagtggcg 780

ggcgtgggct ctgacgtcac cattgttggt atcggtgatg gccaggcaca tgcgaaagtt 840

ggtttcttcc agagtcctta tgaggcatcg gttacggtac cttattgggg cgctcgtaat 900

gaactgatcg aattgatcga tctggcgcat gctggtattt tcgacattgc cgttgagacc 960

ttctctttgg ataatggtgc agaggcctat cgtcgcctgg ctgcgggcac actgtcaggc 1020

cgtgcggtag tcgtcccggg cctgtaatga 1050

<210>6

<211>349

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>6

Met Lys Ala Ile Gln Tyr Thr Arg Ile Gly Ala Glu Pro Glu Leu Thr

1 5 10 15

Glu Ile Pro Lys Pro Glu Pro Gly Pro Gly Glu Val Leu Leu Glu Val

20 25 30

Thr Ala Ala Gly Val Cys His Ser Asp Asp Phe Ile Met Ser Leu Pro

35 40 45

Glu Glu Gln Tyr Thr Tyr Gly Leu Pro Leu Thr Leu Gly His Glu Gly

50 55 60

Ala Gly Lys Val Ala Ala Val Gly Glu Gly Val Glu Gly Leu Asp Ile

65 70 75 80

Gly Thr Asn Val Val Val Tyr Gly Pro Trp Gly Cys Gly Asn Cys Trp

85 90 95

His Cys Ser Gln Gly Leu Glu Asn Tyr Cys Ser Arg Ala Gln Glu Leu

100 105 110

Gly Ile Asn Pro Pro Gly Leu Gly Ala Pro Gly Ala Leu Ala Glu Phe

115 120 125

Met Ile Val Asp Ser Pro Arg His Leu Val Pro Ile Gly Asp Leu Asp

130 135 140

Pro Val Lys Thr Val Pro Leu Thr Asp Ala Gly Leu Thr Pro Tyr His

145 150 155 160

Ala Ile Lys Arg Ser Leu Pro Lys Leu Arg Gly Gly Ser Tyr Ala Val

165 170 175

Val Ile Gly Thr Gly Gly Leu Gly His Val Ala Ile Gln Leu Leu Arg

180 185 190

His Leu Ser Ala Ala Thr Val Ile Ala Leu Asp Val Ser Ala Asp Lys

195 200 205

Leu Glu Leu Ala Thr Lys Val Gly Ala His Glu Val Val Leu Ser Asp

210 215 220

Lys Asp Ala Ala Glu Asn Val Arg Lys Ile Thr Gly Ser Gln Gly Ala

225 230 235 240

Ala Leu Val Leu Asp Phe Val Gly Tyr Gln Pro Thr Ile Asp Thr Ala

245 250 255

Met Ala Val Ala Gly Val Gly Ser Asp Val Thr Ile Val Gly Ile Gly

260 265 270

Asp Gly Gln Ala His Ala Lys Val Gly Phe Phe Gln Ser Pro Tyr Glu

275 280 285

Ala Ser Val Thr Val Pro Tyr Trp Gly Ala Arg Asn Glu Leu Ile Glu

290 295 300

Leu Ile Asp Leu Ala His Ala Gly Ile Phe Asp Ile Ala Val Glu Thr

305 310 315 320

Phe Ser Leu Asp Asn Gly Ala Glu Ala Tyr Arg Arg Leu Ala Ala Gly

325 330 335

Thr Leu Ser Gly Arg Ala Val Val Val Pro Gly Leu

340 345

<210>7

<211>1050

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>7

atgaccacgg aaaaaaccgt agtgttcgtg tcaggcgcga ccggttttat tgctctgcac 60

gtggtagatg acctgctgaa aactggttac aaagtaattg gttccggtcg ttctcaggaa 120

aaaaatgacg gtttgctgaa gaagttcaag tccaacccga atctgagcat ggaaattgtg 180

gaagatattg cggcaccaaa cgccttcgat aaagtattcc agaaacatgg taaagaaatt 240

aaagtggtcc tgcatatcgc gtccccggtc catttcaaca ctaccgattt cgaaaaagac 300

ttactgatcc cggcggtaaa cggtaccaaa tctattttgg aagcaattaa gaactatgcc 360

gcagacaccg tggaaaaagt ggttattact tcatctgttg ccgcgttggc ctctccgggt 420

gatatgaaag ataccagctt cgtggttaac gaagaatcct ggaataaaga cacctgggaa 480

tcgtgtcagg cgaatgctgt gtccgcttat tgcggttcta aaaaattcgc agagaaaacg 540

gcgtgggact tcttggaaga aaaccagagc agcattaaat ttactctgtc cacgattaac 600

ccaggcttcg tttttggtcc gcagctgttc gccgactcct tgcgcaatgg tattaactct 660

agcagtgcga ttattgcgaa cctggtgtcg tataaattag gggataactt ctacaattat 720

agcggcccgt ttatcgacgt ccgtgacgtt tccaaagctc atctgctggc atttgagaaa 780

cctgaatgcg ccggtcagcg cctgtttctg tgcgaggata tgttctgttc ccaggaagcc 840

ctggacattc tgaacgaaga atttccacag ctgaagggca agatcgcaac gggcgaacct 900

ggcagcggct cgaccttcct gactaaaaat tgttgcaaat gcgacaatcg taaaactaaa 960

aacttgctgg gcttccagtt caacaaattc cgcgactgca ttgtcgatac tgcgtcccag 1020

ttgctggaag tgcaaagcaa aagctaatga 1050

<210>8

<211>349

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>8

Met Thr Thr Glu Lys Thr Val Val Phe Val Ser Gly Ala Thr Gly Phe

1 5 10 15

Ile Ala Leu His Val Val Asp Asp Leu Leu Lys Thr Gly Tyr Lys Val

20 25 30

Ile Gly Ser Gly Arg Ser Gln Glu Lys Asn Asp Gly Leu Leu Lys Lys

35 40 45

Phe Lys Ser Asn Pro Asn Leu Ser Met Glu Ile Val Glu Asp Ile Ala

50 55 60

Ala Pro Asn Ala Phe Asp Lys Val Phe Gln Lys His Gly Lys Glu Ile

65 70 75 80

Lys Val Val Leu His Ile Ala Ser Pro Val His Phe Asn Thr Thr Asp

85 90 95

Phe Glu Lys Asp Leu Leu Ile Pro Ala Val Asn Gly Thr Lys Ser Ile

100 105 110

Leu Glu Ala Ile Lys Asn Tyr Ala Ala Asp Thr Val Glu Lys Val Val

115 120 125

Ile Thr Ser Ser Val Ala Ala Leu Ala Ser Pro Gly Asp Met Lys Asp

130 135 140

Thr Ser Phe Val Val Asn Glu Glu Ser Trp Asn Lys Asp Thr Trp Glu

145 150 155 160

Ser Cys Gln Ala Asn Ala Val Ser Ala Tyr Cys Gly Ser Lys Lys Phe

165 170 175

Ala Glu Lys Thr Ala Trp Asp Phe Leu Glu Glu Asn Gln Ser Ser Ile

180 185 190

Lys Phe Thr Leu Ser Thr Ile Asn Pro Cly Phe Val Phe Gly Pro Gln

195 200 205

Leu Phe Ala Asp Ser Leu Arg Asn Gly Ile Asn Ser Ser Ser Ala Ile

210 215 220

Ile Ala Asn Leu Val Ser Tyr Lys Leu Gly Asp Asn Phe Tyr Asn Tyr

225 230 235 240

Ser Gly Pro Phe Ile Asp Val Arg Asp Val Ser Lys Ala His Leu Leu

245 250 255

Ala Phe Glu Lys Pro Glu Cys Ala Gly Gln Arg Leu Phe Leu Cys Glu

260 265 270

Asp Met Phe Cys Ser Gln Glu Ala Leu Asp Ile Leu Asn Glu Glu Phe

275 280 285

Pro Gln Leu Lys Gly Lys Ile Ala Thr Gly Glu Pro Gly Ser Gly Ser

290 295 300

Thr Phe Leu Thr Lys Asn Cys Cys Lys Cys Asp Asn Arg Lys Thr Lys

305 310 315 320

Asn Leu Leu Gly Phe Gln Phe Asn Lys Phe Arg Asp Cys Ile Val Asp

325 330 335

Thr Ala Ser Gln Leu Leu Glu Val Gln Ser Lys Ser

340 345

<210>9

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>9

atgccggcaa cgttaaaaaa cagcagtgct accttaaaat taaacacagg tgcgagcatt 60

cctgtcctgg ggttcggcac ctggcgctct gtcgataaca acggctatca tagtgtaatt 120

gcggcgctga aagcggggta ccgtcatatc gatgctgcgg ccatctatct gaatgaagaa 180

gaagtcggcc gtgcgatcaa ggactccggt gttcctcgtg aagaaatttt tattaccacc 240

aaactgtggg gcaccgaaca acgcgatcca gaagcagccc tgaacaaatc tctgaaacgt 300

ctgggtctgg actatgtgga cctgtatctg atgcactggc cggtccctct gaaaacagac 360

cgtgtaactg acggtaacgt cctgtgcatc ccgaccctgg aagatggcac cgtggacatc 420

gataccaaag agtggaattt tattaaaacc tgggaactga tgcaggaatt gccgaaaact 480

ggtaagacca aagccgtcgg tgtgtccaat ttttccatca acaatatcaa agaactgctg 540

gaatcgccaa ataacaaggt cgttccagca accaatcaga tcgagattca tccgttgctg 600

ccgcaggatg aattaatcgc cttttgtaaa gaaaaaggca ttgtggtcga agcatatagc 660

ccattcggct ccgctaacgc cccgctgctg aaagaacagg cgattatcga tatggccaaa 720

aagcacggcg tcgaaccggc gcaactgatt atcagctggt cgattcagcg cggttatgtg 780

gtattggcca agtccgtaaa tccggagcgt atcgtgtcga actttaagat ttttaccctg 840

ccagaggatg atttcaaaac catctctaac ctgagcaaag tgcacggtac caaacgtgtc 900

gttgacatga aatggggctc atttccgatt tttcaataat ga 942

<210>10

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>10

Met Pro Ala Thr Leu Lys Asn Ser Ser Ala Thr Leu Lys Leu Asn Thr

1 5 10 15

Gly Ala Ser Ile Pro Val Leu Gly Phe Gly Thr Trp Arg Ser Val Asp

20 25 30

Asn Asn Gly Tyr His Ser Val Ile Ala Ala Leu Lys Ala Gly Tyr Arg

35 40 45

His Ile Asp Ala Ala Ala Ile Tyr Leu Asn Glu Glu Glu Val Gly Arg

50 55 60

Ala Ile Lys Asp Ser Gly Val Pro Arg Glu Glu Ile Phe Ile Thr Thr

65 70 75 80

Lys Leu Trp Gly Thr Glu Gln Arg Asp Pro Glu Ala Ala Leu Asn Lys

85 90 95

Ser Leu Lys Arg Leu Gly Leu Asp Tyr Val Asp Leu Tyr Leu Met His

100 105 110

Trp Pro Val Pro Leu Lys Thr Asp Arg Val Thr Asp Gly Asn Val Leu

115 120 125

Cys Ile Pro Thr Leu Glu Asp Gly Thr Val Asp Ile Asp Thr Lys Glu

130 135 140

Trp Asn Phe Ile Lys Thr Trp Glu Leu Met Gln Glu Leu Pro Lys Thr

145 150 155 160

Gly Lys Thr Lys Ala Val Gly Val Ser Asn Phe Ser Ile Asn Asn Ile

165 170 175

Lys Glu Leu Leu Glu Ser Pro Asn Asn Lys Val Val Pro Ala Thr Asn

180 185 190

Gln Ile Glu Ile His Pro Leu Leu Pro Gln Asp Glu Leu Ile Ala Phe

195 200 205

Cys Lys Glu Lys Gly Ile Val Val Glu Ala Tyr Ser Pro Phe Gly Ser

210 215 220

Ala Asn Ala Pro Leu Leu Lys Glu Gln Ala Ile Ile Asp Met Ala Lys

225 230 235 240

Lys His Gly Val Glu Pro Ala Gln Leu Ile Ile Ser Trp Ser Ile Gln

245 250 255

Arg Gly Tyr Val Val Leu Ala Lys Ser Val Asn Pro Glu Arg Ile Val

260 265 270

Ser Asn Phe Lys Ile Phe Thr Leu Pro Glu Asp Asp Phe Lys Thr Ile

275 280 285

Ser Asn Leu Ser Lys Val His Gly Thr Lys Arg Val Val Asp Met Lys

290 295 300

Trp Gly Ser Phc Pro Ile Phe Gln

305 310

<210>11

<211>1032

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>11

atgtctgtgt tcgtgtcagg cgcgaatggt tttattgctc agcacatcgt agatctgctg 60

ctgaaagaag attacaaagt aattggttcc gcacgttctc aggaaaaagc tgaaaatttg 120

accgaagcct tcggtaacaa cccgaaattt agcatggaag tggtgcctga tattagcaaa 180

ctggatgcct tcgatcatgt attccagaaa catggtaaag atattaaaat cgtcctgcat 240

accgcgtccc cgttttgttt cgatattacc gattccgaac gtgacttact gatcccggcg 300

gtaaacggtg tcaaaggtat tttgcacagt attaagaaat atgccgcaga cagcgtggaa 360

cgcgtggttc tgacttcatc ttacgccgcg gtatttgata tggcgaagga aaacgataag 420

agcctgacct tcaacgaaga atcctggaat ccggcgacct gggaatcgtg tcagagtgat 480

ccggtgaacg cttattgcgg ttctaaaaaa ttcgcagaga aagcagcgtg ggaattcttg 540

gaagaaaacc gtgatagcgt gaaatttgag ctgacagcgg tcaacccagt ttacgttttt 600

ggtccgcaga tgttcgataa agatgttaaa aaacacttga acaccagctg cgaactggtg 660

aactctctga tgcatctgag ccctgaagat aaaattccgg aactgtttgg cggttacatc 720

gacgtccgtg acgttgcgaa agctcatctg gttgcatttc agaaacgtga aacaatcggt 780

cagcgcctga tcgtgtcgga ggcacgtttc acgatgcagg acgttctgga cattctgaac 840

gaagactttc cagtactgaa gggcaatatc ccggtcggca agcctggcag cggcgccacc 900

cataatactc tgggcgccac cctggacaat aaaaaaagca aaaaattgct gggcttcaaa 960

ttccgtaatc tgaaagagac tattgacgat actgcgtccc agatcctgaa attcgaaggt 1020

cgcatttaat ga 1032

<210>12

<211>343

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>12

Met Ser Val Phe Val Ser Gly Ala Asn Gly Phe Ile Ala Gln His Ile

1 5 10 15

Val Asp Leu Leu Leu Lys Glu Asp Tyr Lys Val Ile Gly Ser Ala Arg

20 25 30

Ser Gln Glu Lys Ala Glu Asn Leu Thr Glu Ala Phe Gly Asn Asn Pro

35 40 45

Lys Phe Ser Met Glu Val Val Pro Asp Ile Ser Lys Leu Asp Ala Phe

50 55 60

Asp His Val Phe Gln Lys His Gly Lys Asp Ile Lys Ile Val Leu His

65 70 75 80

Thr Ala Ser Pro Phe Cys Phe Asp Ile Thr Asp Ser Glu Arg Asp Leu

85 90 95

Leu Ile Pro Ala Val Asn Gly Val Lys Gly Ile Leu His Ser Ile Lys

100 105 110

Lys Tyr Ala Ala Asp Ser Val Glu Arg Val Val Leu Thr Ser Ser Tyr

115 120 125

Ala Ala Val Phe Asp Met Ala Lys Glu Asn Asp Lys Ser Leu Thr Phe

130 135 140

Asn Glu Glu Ser Trp Asn Pro Ala Thr Trp Glu Ser Cys Gln Ser Asp

145 150 155 160

Pro Val Asn Ala Tyr Cys Gly Ser Lys Lys Phe Ala Glu Lys Ala Ala

165 170 175

Trp Glu Phe Leu Glu Glu Asn Arg Asp Ser Val Lys Phe Glu Leu Thr

180 185 190

Ala Val Asn Pro Val Tyr Val Phe Gly Pro Gln Met Phe Asp Lys Asp

195 200 205

Val Lys Lys His Leu Asn Thr Ser Cys Glu Leu Val Asn Ser Leu Met

210 215 220

His Leu Ser Pro Glu Asp Lys Ile Pro Glu Leu Phe Gly Gly Tyr Ile

225 230 235 240

Asp Val Arg Asp Val Ala Lys Ala His Leu Val Ala Phe Gln Lys Arg

245 250 255

Glu Thr Ile Gly Gln Arg Leu Ile Val Ser Glu Ala Arg Phe Thr Met

260 265 270

Gln Asp Val Leu Asp Ile Leu Asn Glu Asp Phe Pro Val Leu Lys Gly

275 280 285

Asn Ile Pro Val Gly Lys Pro Gly Ser Gly Ala Thr His Asn Thr Leu

290 295 300

Gly Ala Thr Leu Asp Asn Lys Lys Ser Lys Lys Leu Leu Gly Phe Lys

305 310 315 320

Phe Arg Asn Leu Lys Glu Thr Ile Asp Asp Thr Ala Ser Gln Ile Leu

325 330 335

Lys Phe Glu Gly Arg Ile

340

<210>13

<211>759

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>13

atgaccgatc gtctgaaggg caaagtagcc atcgtaaccg gcgggactct gggtatcggt 60

ttggcaatcg ccgataaatt tgtagaggag ggtgcgaaag tagttattac tggtcgtcac 120

gcggatgtag gtgaaaaggc cgccaaatca atcggcggca ctgatgttat tcgctttgtc 180

cagcacgatg catccgatga agcaggctgg acgaaactgt tcgacaccac cgaggaggca 240

ttcggcccgg ttacgaccgt cgtgaacaat gcagggattg cagtttccaa aagcgttgaa 300

gacactacca cggaggaatg gcgtaaactg ctgtccgtta atctggatgg tgtttttttc 360

ggcacccgtc tgggcattca gcgcatgaaa aataaaggct tgggcgctag catcatcaat 420

atgagcagta ttgaggggtt cgtaggcgat ccgacgctgg gggcatacaa cgcttccaag 480

ggggcggtac gtatcatgtc gaaaagcgca gcgctggatt gcgcactgaa ggactacgat 540

gtgcgtgtca acacagtaca tccgggctat atcaagaccc cgctggtcga tgatctggaa 600

ggtgctgagg aaatgatgtc acagcgtacg aaaaccccta tgggccacat tggcgaaccg 660

aatgacatcg catggatctg tgtgtacctg gcatctgacg aatcgaaatt tgcgacgggt 720

gcagaatttg tggtcgacgg cgggtatacc gcacagtga 759

<210>14

<211>252

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>14

Met Thr Asp Arg Leu Lys Gly Lys Val Ala Ile Val Thr Gly Gly Thr

1 5 10 15

Leu Gly Ile Gly Leu Ala Ile Ala Asp Lys Phe Val Glu Glu Gly Ala

20 25 30

Lys Val Val Ile Thr Gly Arg His Ala Asp Val Gly Glu Lys Ala Ala

35 40 45

Lys Ser Ile Gly Gly Thr Asp Val Ile Arg Phe Val Gln His Asp Ala

50 55 60

Ser Asp Glu Ala Gly Trp Thr Lys Leu Phe Asp Thr Thr Glu Glu Ala

65 70 75 80

Phe Gly Pro Val Thr Thr Val Val Asn Asn Ala Gly Ile Ala Val Ser

85 90 95

Lys Ser Val Glu Asp Thr Thr Thr Glu Glu Trp Arg Lys Leu Leu Ser

100 105 110

Val Asn Leu Asp Gly Val Phe Phe Gly Thr Arg Leu Gly Ile Gln Arg

115 120 125

Met Lys Asn Lys Gly Leu Gly Ala Ser Ile Ile Asn Met Ser Ser Ile

130 135 140

Glu Gly Phe Val Gly Asp Pro Thr Leu Gly Ala Tyr Asn Ala Ser Lys

145 150 155 160

Gly Ala Val Arg Ile Met Ser Lys Ser Ala Ala Leu Asp Cys Ala Leu

165 170 175

Lys Asp Tyr Asp Val Arg Val Asn Thr Val His Pro Gly Tyr Ile Lys

180 185 190

Thr Pro Leu Val Asp Asp Leu Glu Gly Ala Glu Glu Met Met Ser Gln

195 200 205

Arg Thr Lys Thr Pro Met Gly His Ile Gly Glu Pro Asn Asp Ile Ala

210 215 220

Trp Ile Cys Val Tyr Leu Ala Ser Asp Glu Ser Lys Phe Ala Thr Gly

225 230 235 240

Ala Glu Phe Val Val Asp Gly Gly Tyr Thr Ala Gln

245 250

<210>15

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>15

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacacg ttggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtacgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatatagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcgca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacat caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>16

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>16

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Arg Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Ile Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Ala

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Ile Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>17

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>17

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacacg ttggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgcgtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagtcaac cattttttga gtacgtcaaa gaattgagcg aaaaatacat caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>18

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>18

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Arg Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Arg

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Ile Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Ash Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>19

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>19

atgtcttttc atcaacagtt tttcacgctg aataacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacacg ttggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg atcaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtaccg attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcgca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacat caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataactc cgccgcccag aaagtgtaat ga 942

<210>20

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>20

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Arg Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Asp Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Ala

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Ile Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Ser Ala Ala Gln Lys Val

305 310

<210>21

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>21

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatgggca ctggtacacg ttggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg agcaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatataa aactggtaaa gctaaaaaca tcggggtttc caatttcgca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacat caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>22

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>22

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Met Gly Thr Gly Thr Arg Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Thr Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Ala

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Ile Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>23

<211>939

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>23

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacacg ttggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcgca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacat caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggat catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaa 939

<210>24

<211>312

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>24

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Arg Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Ala

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Ile Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Asp His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>25

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>25

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc ttggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcgca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacat caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>26

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>26

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Ala

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Ile Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>27

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>27

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacacg ttggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg agcaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagatct atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcgca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacat caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgcgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacaa cgccgcccag aaagtgtaat ga 942

<210>28

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>28

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Arg Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 130 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Ala

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Ile Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Ala Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Asn Ala Ala Gln Lys Val

305 310

<210>29

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>29

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc ttggtacaaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gcatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcgca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacat caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>30

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>30

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val His

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Ala

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Ile Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>31

<211>936

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>31

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacacg ttggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacacc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcgca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacat caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtg 936

<210>32

<211>312

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>32

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Arg Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Thr Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln lle Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Ala

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Ile Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>33

<211>936

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>33

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacacg ttggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag gttatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcgca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacat caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtg 936

<210>34

<211>312

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>34

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Arg Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Gly Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Ala

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp IIe Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Tle Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>35

<211>936

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>35

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacacg ttggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcgca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaagt caaccagatt 540

gagttctctc cgctcctgca aaaccaaaca ccaggtattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacat caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtg 936

<210>36

<211>312

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>36

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala lle Ile Gly Thr Gly Thr Arg Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Ala

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Leu Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Ile Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>37

<211>936

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>37

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacacg ttggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcgca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacat caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtg 936

<210>38

<211>312

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>38

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Arg Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Ala

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Ile Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>39

<211>936

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>39

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacacg ttggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcgca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacat caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggag catgaaccgc tgcgcgtgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtg 936

<210>40

<211>312

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>40

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Arg Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser LeuThr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Ala

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Ile Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Val Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>41

<211>936

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>41

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacacg ttggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac caaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacat caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcttgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtg 936

<210>42

<211>312

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>42

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Arg Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Lys Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Ile Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>43

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>43

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacacg ttggtataaa aatgaagaaa ctgacgcgac cttctcctat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcgca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ctctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgtgcg aaaaatacat caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>44

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>44

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Arg Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Tyr Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Ala

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Cys Glu Lys Tyr Ile Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>45

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>45

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacacg ttggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcgca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ataagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacat caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagtt gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>46

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>46

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Arg Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Ala

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu His Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Ile Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>47

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>47

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacacg ttggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcgca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacat caaatccgag 720

gcccagatca tcctgcgctg gatcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>48

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>48

Met Ser Phe His Gln Gln Phe Phe Thr Leu Ash Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Arg Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Ala

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Ile Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Ile Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>49

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>49

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacacg ttggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcgcagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcgca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgatcctgca aaaccaaact ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacat caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>50

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>50

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Arg Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Gln Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Ala

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Ile Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Ile Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>51

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>51

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacacg ttggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacacc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcgca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cattcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacat caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>52

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>52

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Arg Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Thr Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Ala

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Ile Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>53

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>53

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc ttggtacaaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gcatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg ccaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagtcaac cattttttga gtacgtcaaa gaattgagcg aaaaatacat caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>54

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>54

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val His

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Ile Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>55

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>55

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatgggca ctggtacacg ttggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agcctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gtggacggtc tggatttagc attgaagaaa atgcgtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagtcaac cattttttga gtacgtcaaa gaattgagcg aaaaatacat caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataactc cgccgcccag aaagtgtaat ga 942

<210>56

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>56

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Met Gly Thr Gly Thr Arg Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Val Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Arg

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Ile Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Ser Ala Ala Gln Lys Val

305 310

<210>57

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>57

atgtcttttc atcaacagtt cttcacgctg aataacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc ttggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcgca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacat caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataactc cgccgcccag aaagtgtaat ga 942

<210>58

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>58

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His lle Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Ala

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Ile Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Ser Ala Ala Gln Lys Val

305 310

<210>59

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>59

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg gaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatataa aactggtaaa gctaaaaaca tcggggtttc caatttcgca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>60

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>60

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Glu Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Thr Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Ala

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>61

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>61

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacacg ttggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacacc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcgggcggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcgca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttctcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>62

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>62

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Arg Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His lle Asp Thr Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Gly Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Ala

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>63

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>63

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacacg ttggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcgca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatc 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>64

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>64

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Arg Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Ala

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>65

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>65

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc ttggtacaaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gcatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagtcaac cattttttga gtacgtcaaa gaattgagcg aaaaatacat caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>66

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>66

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val His

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Ile Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>67

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>67

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacacg ttggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg agcaaatcgt gtatgcgttg aaactaccgg ggattatcca catcgacacc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcgca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatc 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>68

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>68

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Arg Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Thr Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Ala

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>69

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>69

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatgggca ctggtacacg ttggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg agcaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacacc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aacggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcgca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtacggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>70

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>70

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Met Gly Thr Gly Thr Arg Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Thr Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Ala

145 150 155 160

VaI Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly VaI Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg lle Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>71

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>71

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc ttggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcacaggat 660

gacagtcaac cattttttga gtacgtcaaa gaattgagcg aaaaatacat caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aggccccagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>72

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>72

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Ile Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Arg Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>73

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>73

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatgggca ctggtacacg ttggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcgca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgcgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>74

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>74

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Met Gly Thr Gly Thr Arg Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Ala

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Ala Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>75

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>75

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatgggca ctggtacacg ttggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg atcaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcgca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatc 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctgcaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>76

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>76

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Met Gly Thr Gly Thr Arg Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Asp Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Ala

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phc Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Gln His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>77

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>77

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacacg ttggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagtcaac cattttttga gtacgtcaaa gaattgagcg aaaaatacat caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggat catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>78

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>78

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Arg Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Ile Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Asp His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>79

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>79

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatgggca ctggtacacg ttggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcgca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggat catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>80

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>80

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Met Gly Thr Gly Thr Arg Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Ala

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Asp His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>81

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>81

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacacg ttggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgcgtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacat caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataactc cgccgcccag aaagtgtaat ga 942

<210>82

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>82

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Arg Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Arg

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Ile Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Ser Ala Ala Gln Lys Val

305 310

<210>83

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>83

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatgggca ctggtacacg ttggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg agcaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctggc cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgcgtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagtcaac cattttttga gtacgtcaaa gaattgagcg aaaaatacat caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>84

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>84

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Met Gly Thr Gly Thr Arg Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Ala Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Arg

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Ile Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>85

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>85

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatgggca ctggtacacg ttggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg agcaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaagatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcgca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcgta ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>86

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>86

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Met Gly Thr Gly Thr Arg Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Ala

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>87

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>87

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacacg ttggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcgca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatc 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>88

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>88

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Arg Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Ala

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>89

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>89

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacacg ttggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacacc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcgca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacac caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>90

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>90

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Arg Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Thr Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Ala

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Thr Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Va1 Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>91

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>91

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacacg ttggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagtcaac cattttttga gtacgtcaaa gaattgagcg aaaaatacat caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagccccagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataactc cgccgcccag aaagtgtgat ga 942

<210>92

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>92

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Arg Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Ile Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Ser Ala Ala Gln Lys Val

305 310

<210>93

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>93

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacacg ttggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaggtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacag aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta agcctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgagccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataactc cgccgcccag aaagtgtaat ga 942

<210>94

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>94

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Arg Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phc Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Arg Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Ser Ala Ala Gln Lys Val

305 310

<210>95

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>95

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>96

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>96

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg IIe Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>97

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>97

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaggcct 240

cggaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtaccg attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagtcaac cattttttga gtacgtcaaa gaattgagcg aaaaatacat caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>98

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>98

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly lle lle His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Arg Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Ile Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>99

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>99

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc ttggtacaaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg agcaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgcgtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>100

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>100

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Scr Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Arg

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Gh Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Gh

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Ash Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>101

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>101

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacacg ttggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacacc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcgca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aaccccaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt atagattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>102

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>102

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Arg Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Thr Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Ala

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Arg Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>103

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>103

argtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacacg ttggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc actgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacat caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>104

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>104

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Arg Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Ile Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>105

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>105

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacacg ttggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggaggttt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac caaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgttg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacat caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcttgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>106

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>106

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Arg Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Val Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Lys Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu his Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Ile Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>107

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>107

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacacg ttggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg gaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcgca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta agcctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gtaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacat caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>108

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>108

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Arg Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Glu Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Ala

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Ile Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>109

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>109

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacacg ttggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcgca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacac caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>110

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>110

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Arg Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Ala

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Thr Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>111

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>111

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>112

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>112

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>113

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>113

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgggcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>114

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>114

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Gly Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>115

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>115

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa aatgaagaaa ctgatgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacaa attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg gatcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>116

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>116

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asn Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Ile Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>117

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>117

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagctta ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgcgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>118

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>118

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Ala Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>119

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>119

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctgtttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>120

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>120

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Phe Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>121

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>121

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacatcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>122

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>122

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr lle Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>123

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>123

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatcta 360

ttacattccc cgcttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg ccaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgatctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>124

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>124

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>125

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>125

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgagaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

atacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>126

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>126

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>127

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>127

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccactg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

atgcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>128

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>128

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Met Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>129

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>129

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacacg ttggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttctcg 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaataccg gaaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>130

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>130

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Arg Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Ser

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Arg Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>131

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>131

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacacg ttggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttctcc 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacgg caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>132

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>132

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Arg Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Ser

145 150 155 160

Val Glu Asp Leu Gln Arg Tle Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Gly Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>133

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>133

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacacg ttggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcagc 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacca aaaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>134

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>134

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Arg Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Tle Phe Leu Thr Asp Lys Tyr Ser Pro Gln Tle Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Ser

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Gln Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>135

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>135

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccatgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>136

<211>313

<212>PRT

<213>人工序列

<220>

<225>合成构建体

<400>136

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Met Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>137

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>137

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagatat atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa acgtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>138

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>138

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Arg Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>139

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>139

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaaaccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>140

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>140

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Thr Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>141

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>141

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggatggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagacacc cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>142

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>142

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Arg His Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>143

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>143

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa aatgaagaaa ctgacgcgac cttctccaac 120

agtctggttg aacaaatctt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gtcagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>144

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>144

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Leu Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Val Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>145

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>145

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc agaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgccagta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>146

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>146

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Gln Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Gln Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>147

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>147

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttctcc 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aaccccaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>148

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>148

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Ser

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>149

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>149

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg agcaaatcgt gcatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>150

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>150

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val His

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>151

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>151

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtacgcgttg gagctgccgg gaattatcca catcgacgcc 180

gcggaggttt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacgg caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>152

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>152

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Glu Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Val Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Gly Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>153

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>153

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa gtggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaacg ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ctctccgctg ggcccgctgc ggatgaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gagttgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>154

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>154

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Met Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>155

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>155

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc ctggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagctc 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc gggagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>156

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>156

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu Leu Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Glu Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>157

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>157

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc ctggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagaataat ga 942

<210>158

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>158

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Glu

305 310

<210>159

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>159

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg agcaaatcgt gtatgcgttg aaactgccgg ggattatcca cgtcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcgttagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>160

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>160

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Val Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Val Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>161

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>161

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc ctggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gcatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>162

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>162

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val His

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>163

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>163

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccagacattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactgaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>164

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>164

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Asp

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Glu Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>165

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>165

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggaggttt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgcttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>166

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>166

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Val Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>167

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>167

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctagaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>168

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>168

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Arg Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>169

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>169

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc ctggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>170

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>170

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Gln Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>171

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>171

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacagtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgcctgttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>172

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>172

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Ser Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>173

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>173

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacacc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcgg tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgttte gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>174

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>174

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Thr Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Val Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Tle Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>175

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>175

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaataccg caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataactc tgccgcccag aaagtgtaat ga 942

<210>176

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>176

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Arg Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Ser Ala Ala Gln Lys Val

305 310

<210>177

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>177

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc ctggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgcttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgagagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>178

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>178

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Arg Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>179

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>179

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc ggttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>180

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>180

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Arg

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>181

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>181

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacga caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>182

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>182

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asp Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>183

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>183

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca cattgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaggcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tccccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataactc tgccgcccag aaagtgtaat ga 942

<210>184

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>184

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Ser Ala Ala Gln Lys Val

305 310

<210>185

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>185

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>186

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>186

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>187

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>187

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac caaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaagc cgcgcaggat 660

gacggccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>188

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>188

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Lys Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Ala Ala Gln Asp Asp Gly Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>189

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>189

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa gtggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacgg caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>190

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>190

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Gly Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>191

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>191

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccatc cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>192

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>192

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser His Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>193

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>193

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac caaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttatatggca aatataactc tgccgcccag aaagtgtaat ga 942

<210>194

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>194

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Lys Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Ser Ala Ala Gln Lys Val

305 310

<210>195

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>195

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc ctggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>196

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>196

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>197

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>197

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttggc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgtttgtttc gaaggaagtg aatggcctaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>198

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>198

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>199

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>199

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa gtggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>200

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>200

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>201

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>201

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

attatcggca ctggtacaaa gtggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacgg caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>202

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>202

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Gly Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>203

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>203

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgactgcc 60

attatcggca ctggtacaaa gtggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtacgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgLttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacgg caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>204

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>204

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Thr Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Gly Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>205

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>205

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggaggttt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>206

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>206

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Val Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>207

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>207

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa gtggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg gaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca gatataacta cgccgcccag aaagtgtaat ga 942

<210>208

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>208

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Glu Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Arg

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>209

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>209

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaataccg caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>210

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>210

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Arg Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>211

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>211

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccagacattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac caccLcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataactc tgccgcccaa aaagtgtaat ga 942

<210>212

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>212

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Asp

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Ser Ala Ala Gln Lys Val

305 310

<210>213

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>213

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc ctggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaataccg caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>214

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>214

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Arg Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>215

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>215

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgegttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac caaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagagaac cgcgcaggat 660

gacagccaac cattctttga gtacgtcaaa gaattgagcg aaaaatacgg caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>216

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>216

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Lys Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Arg Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Gly Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Tle Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>217

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>217

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ctctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacgg caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>218

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>218

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Gly Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>219

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>219

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattgtcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgcta ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>220

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>220

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Val His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>221

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>221

atgtcttttc accaacagtt tttcacactg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggaggttt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>222

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>222

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Val Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>223

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>223

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta agcctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattctttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaga cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatacaacta cgccgcccag aaagtgtaat ga 942

<210>224

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>224

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Arg Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>225

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>225

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaaggg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>226

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>226

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Gly Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>227

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>227

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggcgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>228

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>228

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>229

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>229

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccataca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagcg gggtctggaa catgaaccgc tgcgcctgta ctggaataag 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>230

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>230

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn His Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Arg Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>231

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>231

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaaccac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

ggtatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacgg caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>232

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>232

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Pro Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Gly Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Gly Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>233

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>233

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacca cgccgcccag aaagtgtaat ga 942

<210>234

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>234

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn His Ala Ala Gln Lys Val

305 310

<210>235

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>235

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtttggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>236

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>236

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>237

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>237

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa gtggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttctcc 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>238

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>238

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Ser

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>239

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>239

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa gtggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aagctgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggcaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aaccggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggag catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataactc tgccgcccag aaagtgtaat ga 942

<210>240

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>240

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Thr Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Ser Ala Ala Gln Lys Val

305 310

<210>241

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>241

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa aatgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacgg attatgttga tttatatctg 360

attcattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttctcc 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgcccagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>242

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>242

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Gle Gly Thr Gly Thr Lys Trp Tyr Lys Asn Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Ser

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>243

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>243

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa gtggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac caaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccactgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacgg caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataactc tgccgcccag aaagtgtaat ga 942

<210>244

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>244

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Lys Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Gly Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Ser Ala Ala Gln Lys Val

305 310

<210>245

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>245

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa gtggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgtttgttac gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>246

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>246

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Phe Val Thr Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Glu Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>247

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>247

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc ctggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttctcc 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>248

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>248

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Ser

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>249

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>249

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa gtggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtacgcgttg aagctgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aaccggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>250

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>250

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Thr Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>251

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>251

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa gtggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggcaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacgg caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtataat ga 942

<210>252

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>252

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Gly Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Tle Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>253

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>253

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa gtggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatatagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttctcc 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>254

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>254

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Ile Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Ser

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>255

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>255

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc ctggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtacgcgttg aagctgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttctcc 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt ataaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>256

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>256

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Ser

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>257

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>257

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa gtggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtacgcgttg aagctgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgtttgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aaccggtaaa gctaaaaaca tcggggtttc caatttctcc 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>258

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>258

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Thr Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Ser

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>259

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>259

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattateca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>260

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>260

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>261

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>261

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgcgtgtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt acaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>262

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>262

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Arg Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>263

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>263

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt acaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaataccg caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>264

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>264

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Arg Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>265

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>265

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacaaa atggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggatgaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>266

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>266

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Lys Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Met Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Gln Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>267

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>267

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgttcgtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aaccggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgcgtgtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt acaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>268

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>268

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Phe Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Thr Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Arg Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>269

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>269

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

accatcggca ctggtacagc gtggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt acaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>270

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>270

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Thr Ile Gly Thr Gly Thr Ala Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>271

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>271

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaataccg caaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>272

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>272

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Arg Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>273

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>273

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ttacattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt acaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>274

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>274

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Tyr Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>275

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>275

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>276

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>276

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>277

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>277

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa cccgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>278

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>278

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Pro Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>279

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>279

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcggtcgcc 60

atcatcggca ctggtacagc gtggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg atcaaatcgt gtatgcgttg aaactgccgg ggatcatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtcgtgcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggaattagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgctcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaatccgag 720

gcccaggtga tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggac catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>280

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>280

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Val Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Asp Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Arg Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Glu Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Leu Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Val Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Asp His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>281

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>281

atgtcttttc accaagaatt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

accctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctata cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcagcaacac 600

gacatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac atcttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>282

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>282

Met Ser Phe His Gln Glu Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Thr Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Gln His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Ile Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>283

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>283

atgtcttttc accaagaatt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

accctggttg aacaattagt gtatgcgttg aaactgccgg gggttatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcagcaacac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>284

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>284

Met Ser Phe His Gln Glu Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Thr Leu Val Glu Gln Leu Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Val Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Gln His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>285

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>285

atgtcttttc accaagaatt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

accctggttg aacaattagt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ctgcattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagg agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcagcaacac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaaaccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac atcttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>286

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>286

Met Ser Phe His Gln Glu Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Thr Leu Val Glu Gln Leu Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Glu

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Gln His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Thr Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Ile Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>287

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>287

atgtcttttc accaagaatt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaattagt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaaaccgag 720

gcccagatct tactgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>288

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>288

Met Ser Phe His Gln Glu Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Leu Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Thr Glu

225 230 235 240

Ala Gln Ile Leu Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>289

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>289

atgtcttttc accaagaatt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaaaccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tacgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>290

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>290

Met Ser Phe His Gln Glu Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Thr Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>291

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>291

atgtcttttc accaagaatt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

accctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac atcttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>292

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>292

Met Ser Phe His Gln Glu Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Thr Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Ile Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>293

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>293

atgtcttttc accaagaatt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcc agaaatacaa taaaaccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aaacctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>294

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>294

Met Ser Phe His Gln Glu Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Gln Lys Tyr Asn Lys Thr Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>295

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>295

atgtcttttc accaagaatt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca cctggacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

ctgcattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcagcaacac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaatccgag 720

gcccagatct tactgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>296

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>296

Met Ser Phe His Gln Glu Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Leu Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Leu His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Gln His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Leu Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>297

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>297

atgtcttttc accaagaatt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaattagt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcagcaacac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaaaccgag 720

gcccagatct tactgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>298

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>298

Met Ser Phe His Gln Glu Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Leu Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Gln His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Thr Glu

225 230 235 240

Ala Gln Ile Leu Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>299

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>299

atgtcttttc accaagaatt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca cctggacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttatcac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaaaccgag 720

gcccagatct tactgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>300

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>300

Met Ser Phe His Gln Glu Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Leu Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Ile Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Thr Glu

225 230 235 240

Ala Gln Ile Leu Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>301

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>301

atgtcttttc accaagaatt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaattagt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaaaccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>302

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>302

Met Ser Phe His Gln Glu Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Leu Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Thr Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Tle Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>303

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>303

atgtcttttc accaagaatt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag cgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac atcttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>304

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>304

Met Ser Phe His Gln Glu Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Ile Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>305

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>305

atgtcttttc accaagaatt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaattagt gtatgcgttg aaactgccgg ggattatcca cctggacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagg agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccacccag aaagtgtaat ga 942

<210>306

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>306

Met Ser Phe His Gln Glu Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Leu Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Leu Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Glu

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Thr Gln Lys Val

305 310

<210>307

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>307

atgtcttttc accaagaatt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagg agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tggaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcagcaacac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaaaccgag 720

gcccagatct tactgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aacataacta cgccgcccag aaagtgtaat ga 942

<210>308

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>308

Met Ser Phe His Gln Glu Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Glu

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Glu Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Gln His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Thr Glu

225 230 235 240

Ala Gln Ile Leu Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

His Asn Tyr Ala Ala Gln Lys Val

305 310

<210>309

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>309

atgtcttttc accaagaatt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

accctggttg aacaattagt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtataat ga 942

<210>310

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>310

Met Ser Phe His Gln Glu Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Thr Leu Val Glu Gln Leu Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>311

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>311

atgtcttttc accaagaatt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa agtgaagaaa ctgacgcgac cttctccaat 120

accctggttg aacaattagt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgcta ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>312

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>312

Met Ser Phe His Gln Glu Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Ser Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Thr Leu Val Glu Gln Leu Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>313

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>313

atgtcttttc accaagaatt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa cccgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaattagt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttatcac ggataaatat tctccgcaga ttaaaatgag cgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata trctccgcta ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaaaccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtataat ga 942

<210>314

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>314

Met Ser Phe His Gln Glu Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Pro Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Leu Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Ile Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Thr Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>315

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>315

atgtcttttc accaacagtt tttcacgctg aacaacggcaataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa cccgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagtggt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>316

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>316

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Pro Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Trp Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>317

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>317

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa cccgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagtggt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>318

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>318

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Pro Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Trp Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>319

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>319

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa cccgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgtg gtggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>320

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>320

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Pro Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Trp Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>321

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>321

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa cccgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

aggtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>322

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>322

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Pro Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Arg Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>323

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>323

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa cccgaagaaa ctgacgcgac cttetccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

aagtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>324

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>324

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Pro Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Lys Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>325

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>325

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa cccgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagtggt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgtg gtggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>326

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>326

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Pro Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Trp Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Trp Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>327

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>327

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa cccgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagtggt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgtg gtggaataaa 900

aagtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>328

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>328

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Pro Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Trp Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Trp Trp Asn Lys Lys Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>329

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>329

atgtcttttc accaagaatt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa cccgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaattagt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagtggt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttatcac ggataaatat tctccgcaga ttaaaatgag cgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgcta ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaaaccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtataat ga 942

<210>330

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>330

Met Ser Phe His Gln Glu Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Pro Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Leu Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Trp Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Ile Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Thr Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>331

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>331

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa cccgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagtggt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgtg gtggaataaa 900

gcgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>332

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>332

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Pro Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Trp Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Trp Trp Asn Lys Ala Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>333

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>333

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa cccgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagtggt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgtg gtggaataaa 900

tcgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>334

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>334

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Pro Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Trp Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Trp Trp Asn Lys Ser Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>335

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>335

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa cccgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagtggt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgtg gtggaataaa 900

gagtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>336

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>336

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Pro Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Trp Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Trp Trp Asn Lys Glu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>337

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>337

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa cccgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagtggt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgtg gtggaataaa 900

ccttatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>338

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>338

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Pro Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Trp Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Trp Trp Asn Lys Pro Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>339

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>339

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa cccgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagtggt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggcctggaa catgaaccgc tgcgcctgtg gtggaataaa 900

cagtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>340

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>340

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Pro Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Trp Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Trp Trp Asn Lys Gln Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>341

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>341

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa cccgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagtggt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ttggaataaa 900

gagtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>342

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>342

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Pro Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Trp Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Glu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>343

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>343

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa cccgaagaaa ctgacgcgac cttctccaat 120

ggtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagtggt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

gcgtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>344

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>344

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Pro Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Gly Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Trp Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Ala Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>345

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>345

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa cccgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagtggt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgtt ttggaataaa 900

gagtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>346

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>346

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Pro Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Trp Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Phe Trp Asn Lys Glu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>347

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>347

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa cccgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagtggt atggaaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggcctggaa catgaaccgc tgcgcctgtg gtggaataaa 900

cagtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>348

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>348

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Pro Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Trp Tyr

50 55 60

Gly Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Trp Trp Asn Lys Gln Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>349

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>349

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa cccgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagtggt attcgaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggcctggaa catgaaccgc tgcgcctgtg gtggaataaa 900

cagtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>350

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>350

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Pro Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Trp Tyr

50 55 60

Ser Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Tle Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Trp Trp Asn Lys Gln Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>351

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>351

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa cccgaagaaa ctgacgtgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagtggt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggcctggaa catgaaccgc tgcgcctgtg gtggaataaa 900

cagtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>352

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>352

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Pro Glu

20 25 30

Glu Thr Asp Val Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Trp Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Trp Trp Asn Lys Gln Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>353

<211>943

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>353

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa cccgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagtggt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggcctggaa catgaaccgc tgcgcctgtg gtggaataaa 900

cagtatggca aatataacta cgccgcccga gaaagtgtaa tga 943

<210>354

<211>314

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>354

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Pro Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Trp Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Trp Trp Asn Lys Gln Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Arg Glu Ser Val Met

305 310

<210>355

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>355

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa cccgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagtggt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cacgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggcctggaa catgaaccgc tgcgcctgtg gtggaataaa 900

cagtatggca aatataacta cgccgcccag aaagtgtaat ga 942

<210>356

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>356

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Pro Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Trp Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Set Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Thr Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Trp Trp Asn Lys Gln Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>357

<211>943

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>357

atgtcttttc accaacagtt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa cccgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaaatcgt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagtggt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttctgac ggataaatat tctccgcaga ttaaaatgag tgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgctg ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaatccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggcctggaa catgaaccgc tgcgcctgtg gtggaataaa 900

cagtatggca aatataacta cgccgcccca gaaagtgtaa tga 943

<210>358

<211>314

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>358

Met Ser Phe His Gln Gln Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Pro Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Ile Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Trp Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Leu Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Ser Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Trp Trp Asn Lys Gln Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Pro Glu Ser Val Met

305 310

<210>359

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

<400>359

atgtcttttc accaagaatt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa cccgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaattagt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagtggt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttatcac ggataaatat tctccgcaga ttaaaatgag cgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgcta ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaaaccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgta ctggaataaa 900

gagtatggca aatataacta cgccgcccag aaagtataat ga 942

<210>360

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>360

Met Ser Phe His Gln Glu Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Pro Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Leu Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Trp Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Ile Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Thr Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Tyr Trp Asn Lys Glu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>361

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atgtcttttc accaagaatt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa cccgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaattagt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagattt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttatcac ggataaatat tctccgcaga ttaaaatgag cgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgcta ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaaaccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgtg gtggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtataat ga 942

<210>362

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Met Ser Phe His Gln Glu Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Pro Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Leu Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Ile Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Ile Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Thr Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Trp Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>363

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atgtcttttc accaagaatt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa cccgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaattagt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagtggt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttatcac ggataaatat tctccgcaga ttaaaatgag cgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgcta ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaaaccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgtg gtggaataaa 900

ttgtatggca aatataacta cgccgcccag aaagtataat ga 942

<210>364

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

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Met Ser Phe His Gln Glu Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Pro Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Leu Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Trp Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Ile Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Thr Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Trp Trp Asn Lys Leu Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

<210>365

<211>942

<212>DNA

<213>人工序列

<220>

<223>合成构建体

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atgtcttttc accaagaatt tttcacgctg aacaacggca ataaaatccc ggcgattgcc 60

atcatcggca ctggtacagc gtggtataaa cccgaagaaa ctgacgcgac cttctccaat 120

agtctggttg aacaattagt gtatgcgttg aaactgccgg ggattatcca catcgacgcc 180

gcggagtggt atcgcaccta cccggaagtg ggtaaagcac tgtccctgac cgaaaagcct 240

cgtaacgcga tttttatcac ggataaatat tctccgcaga ttaaaatgag cgactcccct 300

gcggacggtc tggatttagc attgaagaaa atgggtacag attatgttga tttatatctg 360

attcattccc cgttagtttc gaaggaagtg aatggcttaa gcttagaaga ggcttggaaa 420

gatatggagc agttatacaa aagtggtaaa gctaaaaaca tcggggtttc caatttcaca 480

gtggaagacc tgcaacgtat cctgaaagtc gctgaagtta aacctcaggt caaccagatt 540

gagttctctc cgttcctgca aaaccaaaca ccaggcattt gcaaattctg tcaggagcac 600

gatatcctgg tggaagcata ttctccgcta ggcccgctgc ggaagaaaac cgcgcaggat 660

gacagccaac cattttttga gtacgtcaaa gaattgagcg aaaaatacaa taaaaccgag 720

gcccagatca tcctgcgctg ggtcactaaa cgcggtgtgc tgccagttac cacctcttca 780

aagcctcagc gcattagcga tgctcagaac ctgttttcct tcgacctgac agcggaagag 840

gttgataaaa tcacggagct gggtctggaa catgaaccgc tgcgcctgtg gtggaataaa 900

cagtatggca aatataacta cgccgcccag aaagtataat ga 942

<210>366

<211>313

<212>PRT

<213>人工序列

<220>

<223>合成构建体

<400>366

Met Ser Phe His Gln Glu Phe Phe Thr Leu Asn Asn Gly Asn Lys Ile

1 5 10 15

Pro Ala Ile Ala Ile Ile Gly Thr Gly Thr Ala Trp Tyr Lys Pro Glu

20 25 30

Glu Thr Asp Ala Thr Phe Ser Asn Ser Leu Val Glu Gln Leu Val Tyr

35 40 45

Ala Leu Lys Leu Pro Gly Ile Ile His Ile Asp Ala Ala Glu Trp Tyr

50 55 60

Arg Thr Tyr Pro Glu Val Gly Lys Ala Leu Ser Leu Thr Glu Lys Pro

65 70 75 80

Arg Asn Ala Ile Phe Ile Thr Asp Lys Tyr Ser Pro Gln Ile Lys Met

85 90 95

Ser Asp Ser Pro Ala Asp Gly Leu Asp Leu Ala Leu Lys Lys Met Gly

100 105 110

Thr Asp Tyr Val Asp Leu Tyr Leu Ile His Ser Pro Leu Val Ser Lys

115 120 125

Glu Val Asn Gly Leu Ser Leu Glu Glu Ala Trp Lys Asp Met Glu Gln

130 135 140

Leu Tyr Lys Ser Gly Lys Ala Lys Asn Ile Gly Val Ser Asn Phe Thr

145 150 155 160

Val Glu Asp Leu Gln Arg Ile Leu Lys Val Ala Glu Val Lys Pro Gln

165 170 175

Val Asn Gln Ile Glu Phe Ser Pro Phe Leu Gln Asn Gln Thr Pro Gly

180 185 190

Ile Cys Lys Phe Cys Gln Glu His Asp Ile Leu Val Glu Ala Tyr Ser

195 200 205

Pro Leu Gly Pro Leu Arg Lys Lys Thr Ala Gln Asp Asp Ser Gln Pro

210 215 220

Phe Phe Glu Tyr Val Lys Glu Leu Ser Glu Lys Tyr Asn Lys Thr Glu

225 230 235 240

Ala Gln Ile Ile Leu Arg Trp Val Thr Lys Arg Gly Val Leu Pro Val

245 250 255

Thr Thr Ser Ser Lys Pro Gln Arg Ile Ser Asp Ala Gln Asn Leu Phe

260 265 270

Ser Phe Asp Leu Thr Ala Glu Glu Val Asp Lys Ile Thr Glu Leu Gly

275 280 285

Leu Glu His Glu Pro Leu Arg Leu Trp Trp Asn Lys Gln Tyr Gly Lys

290 295 300

Tyr Asn Tyr Ala Ala Gln Lys Val

305 310

Claims

1.一种酮还原酶，其源于酿酒酵母的野生型酮还原酶，能立体选择地还原5-羟基-3-氧代己酸酯的3-氧代基团以产生对应的顺式3，5-二羟基己酸酯，所述酮还原酶与SEQ ID NO：2的野生型酮还原酶相比具有改进的性质。

2.根据权利要求1所述的酮还原酶，其中所述改进的性质是比酮还原酶活性增加。

3.根据权利要求2所述的酮还原酶，其具有的比酮还原酶活性比野生型酮还原酶的比酮还原酶活性大至少约1.5-300倍。

4.根据权利要求1所述的酮还原酶，其中所述改进的性质是热稳定性增加。

5.根据权利要求1所述的酮还原酶，其与SEQ ID NO：2相比在第63位包括芳香族氨基酸。

6.根据权利要求5所述的酮还原酶，其中所述芳香族氨基酸是色氨酸。

7.根据权利要求1所述的酮还原酶，其包括与SEQ ID NO：2具有至少约95％同一性的氨基酸序列。

8.根据权利要求1所述的酮还原酶，其包括下述氨基酸序列：(a)与SEQ ID NO：2具有至少90％同一性，且(b)具有下述特征中的一个或多个：

X⁶是极性或酸性氨基酸残基；

X²⁷是脂肪族或碱性氨基酸残基；

X³¹是包含羟基的或脂肪族氨基酸残基；

X³⁶是小氨基酸残基；

X⁴⁸是碱性氨基酸残基；

X⁶³是疏水性或芳香族氨基酸残基；

X⁶⁵是包含羟基的或小氨基酸残基；

X⁸⁶是脂肪族或疏水性氨基酸残基；

X¹²⁵是脂肪族或芳香族氨基酸残基；

X¹⁵²是碱性氨基酸残基；

X¹⁶⁰是包含羟基的或小氨基酸残基；

X¹⁶⁵是极性或酸性氨基酸残基；

X¹⁹⁴是芳香族氨基酸或极性亲水性氨基酸残基；

X²¹⁴是极性亲水性氨基酸残基；

X²¹⁸是包含羟基的氨基酸残基；

X²³⁴是极性亲水性氨基酸残基；

X²⁴⁸是脂肪族氨基酸残基；

X²⁵⁰是碱性氨基酸残基；

X²⁶³是酸性或极性氨基酸残基；

X²⁹⁰是酸性氨基酸残基；

X²⁹⁶是脂肪族氨基酸残基；

X²⁹⁷是芳香族氨基酸残基；

X³⁰¹是脂肪族或包含羟基的或酸性或亲水性或碱性氨基酸残基；且

X³⁰⁷是芳香族、极性或包含羟基的氨基酸残基。

9.根据权利要求8所述的酮还原酶，其中X⁶³是芳香族氨基酸残基。

10.根据权利要求8所述的酮还原酶，其包括选自以下的一种或多种突变：

X⁶是E；

X²⁷是A或K；

X³¹是S或P；

X³⁶是V；

X⁴⁸是H；

X⁶³是W；

X⁶⁵是G或S；

X⁸⁶是I；

X¹²⁵是L；

X¹⁵²是R；

X¹⁶⁰是T或S；

X¹⁶⁵是E；

X¹⁹⁴是C；

X²¹⁴是R或H；

X²¹⁸是T；

X²³⁴是Q；

X²⁴⁸是I；

X²⁵⁰是R；

X²⁶³是E；

X²⁹⁰是V；

X²⁹⁶是I；

X²⁹⁷是F或W；

X³⁰¹是R、K、A、V、S、T、Y、D、E、P或Q；且

X³⁰⁷是H、N或S。

11.根据权利要求1所述的酮还原酶，其包括选自以下的一种或多种突变：

X⁶是E；

X³¹是P；

X⁴⁴是D；

X⁴⁶是L；

X⁵⁵是V；

X⁵⁶是V；

X⁶⁰是T；

X⁶³是V；

X⁷⁶是M；

X¹⁰³是S；

X¹⁰⁶是I；

X¹¹⁴是G；

X¹²¹是I或M；

X¹⁴⁴是R；

X¹⁴⁸是T；

X¹⁵⁸是H；

X¹⁶⁰是S；

X¹⁶⁵是E；

X²¹⁴是R或H；

X²²³是R或G；

X²³⁴是Q；

X²³⁷是N、G或Q；

X²³⁹是T；

X²⁵³是A；和

X²⁶³是E。

12.根据权利要求11所述的酮还原酶，其包括选自以下的一种或多种突变：

X⁴⁴是D；

X⁴⁶是L；

X⁵⁵是V；

X⁵⁶是V；

X⁶⁰是T；

X⁶³是V；

X⁷⁶是M；

X¹⁰³是S；

X¹⁰⁶是I；

X¹¹⁴是G；

X¹²¹是I或M；

X¹⁴⁴是R；

X¹⁴⁸是T；

X¹⁵⁸是H；

X²²³是R或G；

X²³⁴是Q；

X²³⁷是N、G、R或Q；

X²³⁹是T；且

X²⁵³是A。

13.根据权利要求1所述的酮还原酶，其具有选自以下的氨基酸序列：SEQ ID NO：16、18、20、22、24、26、28、30、32、34、36、38、40、42、44、46、48、50、52、54、56、58、60、62、64、66、68、70、72、74、76、78、80、82、84、86、88、90、92、94、96、98、100、102、104、106、108、110、112、114、116、118、120、122、124、126、128、130、132、134、136、138、140、142、144、146、148、150、152、154、156、158、160、162、164、166、168、170、172、174、176、178、180、182、184、186、188、190、192、194、196、198、200、202、204、206、208、210、212、214、216、218、220、222、224、226、228、230、232、234、236、238、240、242、244、246、248、250、252、254、256、258、260、262、266、268、270、272、274、276、278、280、282、284、286、288、290、292、294、296、298、300、302、304、306、308、310、312、314、316、318、320、322、324、326、328、330、332、334、336、338、340、342、344、346、348、350、352、354、356、358、360、362、364和366。

14.一种多核苷酸，其包括编码根据权利要求1所述的酮还原酶的序列，或在高严格条件下与编码根据权利要求1所述的酮还原酶的序列杂交的序列。

15.根据权利要求14所述的多核苷酸，其选自SEQ ID NO：15、17、19、21、23、25、27、29、31、33、35、37、39、41、43、45、47、49、51、53、55、57、59、61、63、65、67、69、71、73、75、77、79、81、83、85、87、89、91、93、95、97、99、101、103、105、107、109、111、113、115、117、119、121、123、125、127、129、131、133、135、137、139、141、143、145、147、149、151、153、155、157、159、161、163、165、167、169、171、173、175、177、179、181、183、185、187、189、191、193、195、197、199、201、203、205、207、209、211、213、215、217、219、221、223、225、227、229、231、233、235、237、239、241、243、245、247、249、251、253、255、257、259、261、263、265、267、269、271、273、275、277、279、281、283、285、287、289、291、293、295、297、299、301、303、305、307、309、311、313、315、317、319、321、323、325、327、329、331、333、335、337、339、341、343、345、347、349、351、353、355、357、359、361、363和365。

16.一种表达系统，其包括与适于在宿主细胞中指导表达的控制序列可操作地连接的权利要求14所述的多核苷酸。

17.一种宿主细胞，其包括权利要求16所述的表达系统。

18.根据权利要求17所述的宿主细胞，其为大肠杆菌。

19.根据权利要求17所述的宿主细胞，其中所述表达载体所包含的密码子已被优化以在所述宿主细胞中表达。

20.一种用于制备根据式(IIa)的顺式3，5-二羟基己酸酯化合物的工艺：

其中X选自卤素、氰基和-OR⁶，其中R⁶是氢或保护基团，且R¹选自(C1-C12)烃基、(C6-C10)芳基和(C7-C12)芳基烃基，

所述工艺包括立体选择地还原根据结构式(Ia)的5-羟基-3-氧代己酸酯化合物的对映体：

其中X和R¹如对结构式(IIa)所定义；

所述工艺在适合的条件下使用根据权利要求1所述的酮还原酶以将3-氧代基团还原为3-羟基基团。

21.根据权利要求20所述的工艺，其进一步包括从反应混合物回收根据结构式(IIa)的3，5-二羟基己酸酯化合物。

22.根据权利要求20所述的工艺，其中所述5-羟基-3-氧代己酸酯化合物是以结构式(Ia)的对映体大致纯的。

23.根据权利要求20所述的工艺，其用表达所述酮还原酶的全细胞或者用所述细胞的提取物或溶解产物进行。

24.根据权利要求20所述的工艺，其中所述酮还原酶是分离的和/或纯化的，并且所述对映选择性还原反应在所述酮还原酶的辅因子和任选地所述辅因子的再生系统的存在下进行。

25.根据权利要求20所述的工艺，其在约15℃至约75℃范围的温度下进行。

26.根据权利要求20所述的工艺，其在约pH5至pH8范围的pH下进行。

27.根据权利要求20所述的工艺，其中结构式(Ia)所述的5-羟基-3-氧代己酸酯化合物与所述酮还原酶的重量比在约10∶1至200∶1的范围内。

28.根据权利要求20所述的工艺，其中X选自氯、氰基和羟基，且其中R¹是低级烷基或叔丁基。

29.根据权利要求20所述的工艺，其在辅因子和任选地辅因子再生系统的存在下进行。

30.根据权利要求29所述的工艺，其中所述辅因子是NADH和/或NADPH，且其中所述辅因子与所述酮还原酶的重量比在约10∶1至100∶1的范围内。

31.根据权利要求29所述的工艺，其中所述辅因子再生系统包括葡萄糖脱氢酶和葡萄糖；甲酸脱氢酶和甲酸；或异丙醇和仲醇脱氢酶。

32.根据权利要求31所述的工艺，其中所述仲醇脱氢酶是所述酮还原酶。

33.根据权利要求20所述的工艺，其中所述3，5-二羟基己酸酯化合物的制品是以顺式非对映体大致纯的。

34.一种顺式3，5-二羟基己酸酯化合物，其由权利要求20所述的工艺制备。

35.一种反应混合物，其包括根据权利要求1所述的酮还原酶、所述酮还原酶的辅因子和根据结构式(Ia)的底物：

其中X选自卤素、氰基和-OR⁶，其中R⁶是氢或保护基团，且R¹选自(C1-C12)烃基、(C6-C10)芳基和(C7-C12)芳基烃基。

36.一种反应混合物，其包括根据权利要求1所述的酮还原酶、所述酮还原酶的辅因子和根据结构式(IIa)的底物：

37.根据权利要求35或36所述的混合物，其中结构式(Ia)或(IIa)所述的5-羟基-3-氧代己酸酯化合物与所述酮还原酶的重量比在约10∶1至200∶1的范围内。

38.根据权利要求35或36所述的混合物，其中X选自氯、氰基和羟基，且其中R¹是低级烷基或叔丁基。

39.根据权利要求35或36所述的混合物，其中所述辅因子是NADH和/或NADPH，且其中所述辅因子与所述酮还原酶的重量比在约10∶1至100∶1的范围内。

40.根据权利要求35或36所述的混合物，其进一步包括辅因子再生系统。

41.根据权利要求40所述的混合物，其中所述辅因子再生系统包括葡萄糖脱氢酶和葡萄糖；甲酸脱氢酶和甲酸；或异丙醇和仲醇脱氢酶。

42.根据权利要求41所述的混合物，其中所述仲醇脱氢酶是所述酮还原酶。

43.一种合成他汀类化合物的方法，其包括对映选择性还原根据结构式(Ia)的化合物以产生根据结构式(IIa)的化合物作为一个步骤，改进包括用根据权利要求1所述的酮还原酶进行化合物(Ia)至化合物(IIa)的对映选择性还原；

其中结构式(Ia)是：

其中X选自卤素、氰基和-OR⁶，其中R⁶是氢或保护基团，且R¹选自(C1-C12)烃基、(C6-C10)芳基和(C7-C12)芳基烃基；且

其中结构式(IIa)是：

其中X和R¹如对结构式(Ia)所定义。

44.根据权利要求43所述的方法，其中所述他汀类选自阿托伐他汀、罗苏伐他汀和匹伐他汀。

45.一种用于制备根据结构式(IIIa)的受保护的顺式3，5-二羟基-3-氧代己酸酯化合物的工艺：

其中：

X选自卤素、氰基和-OR⁶，其中R⁶是氢或保护基团；

R¹选自(C1-C12)烃基、(C6-C10)芳基和(C7-C12)芳基烃基；且

每个R²都是保护基团，或可选地，所述R²基团可一起形成式-CR³R⁴-的亚烃基桥或-BR⁵-的硼酸酯，其中R³和R⁴各自彼此独立地选自氢、(C1-C12)烃基、(C6-C10)芳基和(C7-C12)芳基烃基，或可选地，R³与R⁴一起形成(C4-C10)环烃基或杂环烃基，且R⁵选自(C1-C12)烃基、(C6-C10)芳基和(C7-C12)芳基烃基，所述工艺包括如下步骤：

(i)立体选择性还原结构式(Ia)的5-羟基-3-氧代己酸酯对映体；

其中结构式(Ia)是：

其中X选自卤素、氰基和-OR⁶，其中R⁶是氢或保护基团，且R¹选自(C1-C12)烃基、(C6-C10)芳基和(C7-C12)芳基烃基；

使用根据权利要求1所述的酮还原酶在合适的条件下将3-氧代基团还原为3-羟基基团，以产生包括根据结构式(IIa)的顺式3，5-二羟基己酸酯化合物的第一反应产物；

其中结构式(IIa)是：

其中X和R¹如对结构式(Ia)所定义；

以及

(ii)保护所述顺式3，5-二羟基己酸酯化合物的羟基基团以产生包括根据结构式(IIIa)的受保护的顺式3，5-二羟基-3-氧代己酸酯化合物的第二反应产物。

46.根据权利要求45所述的工艺，其中R³和R⁴各为甲基。

47.根据权利要求45所述的工艺，其中X选自氯、氰基和羟基。

48.根据权利要求45所述的工艺，其中R¹是低级烷基。

49.根据权利要求48所述的工艺，其中R¹是叔丁基。

50.根据权利要求47所述的工艺，其中X是氯。

51.根据权利要求47所述的工艺，其中X是氰基。

52.根据权利要求47所述的工艺，其中X是羟基。

53.一种受保护的顺式3，5-二羟基-3-氧代己酸酯化合物，其由权利要求45所述的方法制备。