CN112639092A - 差向异构酶及其用途 - Google Patents

差向异构酶及其用途 Download PDF

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CN112639092A
CN112639092A CN201980056241.9A CN201980056241A CN112639092A CN 112639092 A CN112639092 A CN 112639092A CN 201980056241 A CN201980056241 A CN 201980056241A CN 112639092 A CN112639092 A CN 112639092A
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威廉·施罗德
帕德麦什·温基塔苏布拉马尼安
斯里达尔·戈文达拉扬
马克·韦尔奇
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Abstract

本披露提供了可用于从果糖商业规模生产阿洛酮糖的差向异构酶。所披露的酶(“差向异构酶变体”)是多噬伯克霍尔德氏菌CGD1木糖异构酶的变体，所述变体经工程化以具有与亲本酶相比改善约1.5倍至2倍的催化活性。

Description

差向异构酶及其用途
本申请要求于2018年8月8日提交的序列号62/716,204的优先权，将其通过引用以其全文并入本文。本披露中引用的各参考文献、专利和公开的专利申请均通过引用以其全文并入本文。
本申请通过引用并入了创建于2019年8月5日且名为“00820000058sequencelisting”的178kb文本文件，该文本文件是本申请的序列表。
技术领域
本披露总体上涉及阿洛酮糖的生产。
附图说明
图1.显示氨基酸取代对由野生型差向异构酶(204020，SEQ ID NO:6)以及差向异构酶变体230338(SEQ ID NO:16)、277285(SEQ ID NO:90)、277286(SEQ ID NO:92)、277287(SEQ ID NO:94)、277288(SEQ ID NO:96)、277289(SEQ ID NO:98)和277290(SEQ ID NO:100)转换的果糖的级分的影响的图。各对的左条，200mM；各对的右条，50％(w/w)。
图2.显示野生型差向异构酶(204020，SEQ ID NO:6)以及差向异构酶变体230338(SEQ ID NO:16)、277285(SEQ ID NO:90)、277286(SEQ ID NO:92)、277287(SEQ ID NO:94)、277288(SEQ ID NO:96)、277289(SEQ ID NO:98)和277290(SEQ ID NO:100)的表达的图。
图3.显示野生型差向异构酶(204020，SEQ ID NO:6)以及差向异构酶变体230338(SEQ ID NO:16)、277285(SEQ ID NO:90)、277286(SEQ ID NO:92)、277287(SEQ ID NO:94)、277288(SEQ ID NO:96)、277289(SEQ ID NO:98)和277290(SEQ ID NO:100)的比活性的图。各对的左条，200mM；各对的右条，50％DS。
具体实施方式
本披露提供了可用于从果糖商业规模生产阿洛酮糖的差向异构酶。所披露的酶(“差向异构酶变体”)是多噬伯克霍尔德氏菌(Burkholderia multivorans)CGD1木糖异构酶(SEQ ID NO:6)的变体，这些变体经工程化以具有与亲本酶相比改善约1.5倍至2倍的催化活性。下表1鉴别了所附序列表中各差向异构酶变体的氨基酸序列，并提供了编码该变体的核酸序列的实例。表2中总结了各差向异构酶变体和亲本酶(SEQ ID NO:6)之间的氨基酸差异，其中氨基酸编号是指SEQ ID NO:6的氨基酸编号。
表1.差向异构酶变体的氨基酸序列以及编码序列的实例
Figure BDA0002952303820000021
Figure BDA0002952303820000031
Figure BDA0002952303820000041
核酸、载体和宿主微生物
本披露提供了编码上述披露的差向异构酶变体的核酸。序列表提供了编码这些变体的核苷酸序列的实例，但是编码差向异构酶变体的任何核苷酸序列均可使用。
如本领域众所周知的，可以优化核苷酸序列以在多种微生物菌物种或菌株中表达。合适的微生物包括但不限于地衣芽孢杆菌(Bacillus licheniformis)、酿酒酵母(Saccharomyces cerevisiae)、粟酒裂殖酵母(Schizosaccharomyces pombe)、恶臭假单胞菌(Pseudomonas putida)、毕赤酵母属物种(Pichia sp.)、曲霉属物种(Aspergillussp.)、里氏木霉(Trichoderma reesei)、谷氨酸棒状杆菌(Corynebacterium glutamicum)、大肠杆菌(E.coli)和枯草芽孢杆菌(B.subtilis)。含有用于在这些生物中表达任何蛋白质的启动子和其他必要的调控序列的载体是已知的，并且是本领域普通技术人员容易获得的。
编码上述差向异构酶变体的核酸可以包含在载体中，其中编码序列可操作地连接至合适的调控序列以在所需宿主微生物中表达。调控序列包含合适的mRNA核糖体结合位点和用于调节转录和翻译终止的序列，并且可以包括其他元件，诸如启动子或操纵子。一旦被转化到宿主微生物中，载体就可以独立于宿主基因组复制或起作用，或者可以整合至基因组自身中。使用的载体没有特别限制，并且可以是本领域已知的任何载体，只要它可以在宿主中复制即可。
载体可以包含至少一种选择性标记物，诸如抗生素抗性基因。合适的抗生素包括例如阿米卡星、氨比西林、奥格孟汀(augmentin)(阿莫西林加克拉维酸)、头孢唑啉、头孢西丁、头孢他啶、头孢噻呋、先锋霉素(cephalothin)、氯霉素、恩诺沙星、氟苯尼考、庆大霉素、亚胺培南、卡那霉素、青霉素、沙氟沙星(sarafloxicin)、壮观霉素、链霉素、四环素、替卡西林和替米考星。
载体可用于工程化微生物以生产一种或多种上述差向异构酶变体。将载体递送至微生物的方法是众所周知的，并且包括例如磷酸钙转染、DEAE-葡聚糖介导的转染、显微注射、脂质介导的转染、电穿孔、缀合和感染。
生产阿洛酮糖的方法
可以使用本领域众所周知的方法，用本文披露的差向异构酶变体从果糖商业规模生产阿洛酮糖。参见，例如，US 2017/0101637、US2017/0298400、US 2016/0304853和US2016/0281076。
在一些实施例中，将差向异构酶变体或来自包含该差向异构酶变体的微生物的提取物结合至固体基质，并使包含果糖的输入溶液在该基质上通过，以将至少一部分果糖转换为阿洛酮糖，可以从输出流中回收阿洛酮糖。任选地，可以将阿洛酮糖与输出流中的其他组分分离并且可以将其浓缩。
适用于结合酶的许多固体基质是本领域众所周知的，并且包括藻酸盐(例如，海藻酸钠)、AMBERLITETM树脂(例如，
Figure BDA0002952303820000061
Figure BDA0002952303820000062
(西格玛奥德里奇)、
Figure BDA0002952303820000063
树脂或DUOLITETM树脂(例如，A568；陶氏化学(Dow Chemical))；以及Purolite CR8415和ECR 8314(漂莱特公司(Purolite))。另参见WO 2016/160573和WO2016/191267。将差向异构酶固定在支持物上的方法是本领域技术人员众所周知的。参见，例如，美国专利8,375,106。
在其他实施例中，表达差向异构酶变体的微生物可以被透化并固定在藻酸盐珠上，如美国专利8,735,106中所述，或固定在粘土、碳、硅藻土或水凝胶如聚丙烯酰胺上。
本领域技术人员将理解，上述实施例的许多变化和置换都落在所附权利要求书的范围内。
实例1.用于商业生产阿洛酮糖差向异构酶的无标记物枯草芽孢杆菌菌株的生成
此实例描述了表达阿洛酮糖差向异构酶的无标记物枯草芽孢杆菌的生成。简而言之，在第一步中，用编码BMCGD1差向异构酶并包含抗生素抗性标记物的盒转化枯草芽孢杆菌菌株。该盒重组到芽孢杆菌染色体中，并敲除8kb的DNA，包括一个较大的孢子形成基因簇和赖氨酸生物合成基因lysA。在第二步中，将第二个盒重组到枯草芽孢杆菌染色体中，恢复lysA基因并去除编码抗生素抗性的DNA。在枯草芽孢杆菌转化之前，使用来自Keio保藏中心的大肠杆菌菌株39A10使质粒DNA传代。相关的表型是大肠杆菌的另一种野生型K-12菌株中DNA甲基化酶HsdM中的缺失。
详细地，合成5120bp(SEQ ID NO:1；来自爱荷华州科拉维尔IDT公司的合成DNA)的盒，并将其克隆到标准氨比西林抗性pIDT载体中。合成段编码枯草芽孢杆菌染色体上的lysA上游700bp、抗生素标记物cat(651bp)、DNA结合蛋白lacI(1083bp)和阿洛酮糖差向异构酶(894bp)，并包含dacF中700bp的同源性。该载体被转化到大肠杆菌菌株39A10中(Baba等人，2006)，且制备质粒DNA并转化到枯草芽孢杆菌菌株1A751和1A976中。
在补充了氯霉素的LB上选择转化子。pIDT的复制子在大肠杆菌中起作用，但不在诸如枯草芽孢杆菌等革兰氏阳性细菌中奏效。因此出现的菌落代表整合到染色体中的事件。在菌株1A751中，使用平板上的菌落形态来区分单重组和双重组事件。双重组事件将敲除孢子形成所需的基因，而单重组则不会。在LB平板上三天后，能够形成孢子的菌落为棕色和不透明的；孢子形成缺陷菌落更透明。
带有阿洛酮糖差向异构酶盒的枯草芽孢杆菌菌株1A976对组氨酸和赖氨酸是营养缺陷性的，并且可以在木糖诱导后实现非常高的转化效率。通过引物(SEQ ID NO:3，SEQ IDNO:4)和Taq聚合酶(普洛麦格公司(Promega))扩增1925bp合成DNA(SEQ ID NO:2)。此PCR产物编码lysA基因，该基因由于落在差向异构酶盒中和与lacI的500bp的同源性而缺失。此DNA的成功双重组事件应产生对赖氨酸为原养型并且对氯霉素敏感的菌落；即，整个cat基因应均丢失。
在补充了组氨酸的戴维斯基本培养基上选择转化子。通过PCR表征所产生的菌落，并在有和没有氯霉素的情况下划线到LB上。进一步表征扩增所引入的DNA并对氯霉素敏感的菌株，并提取了其染色体DNA。
将含有氯霉素抗性阿洛酮糖的菌株1A751用此染色体DNA进行转化，并在补充了组氨酸的戴维斯基本培养基上进行了选择。在有和没有氯霉素的情况下，将转化子划线到LB上，并如下文所述进行酶学表征。
实例2.差向异构酶蛋白水平的分析
通过在4％-12％Bis-Tris NuPAGE
Figure BDA0002952303820000081
凝胶(英杰公司(Invitrogen))上进行聚丙烯酰胺凝胶电泳，分析粗制和可溶性裂解物中的差向异构酶蛋白水平。使用蛋白定量标准，通过用SimplyBlue(SIMPLYBLUETM)Safe Stain(英杰公司)染色的凝胶的密度测定法确定蛋白水平。
实例3.BMCGD1差向异构酶在枯草芽孢杆菌中的表达
将具有BMCGD1差向异构酶基因的pHT254构建体进行密码子优化以在枯草芽孢杆菌(SEQ ID NO:5)中表达，并用于转化枯草芽孢杆菌菌株DP1077。菌株DP1077是芽孢杆菌遗传储备中心菌株1A976(Em his nprE18 aprE3 eglS(DELTA)102bglT/bglS(DELTA)EVlacA::PxylA-comK)的孢子形成缺陷(ΔspoIIG::ZeoR)衍生物。除了孢子形成缺陷外，分别地，由于nprE和aprE基因的突变，该菌株在分泌中性蛋白酶和枯草杆菌蛋白酶的能力上是缺陷性的。该菌株另外带有如下表达盒，该表达盒将感受态因子comK置于木糖诱导型启动子的控制下，以简单地生产感受态细胞。
选择转化子并在补充了1％葡萄糖和5μg/ml氯霉素的缺乏Mn2+和Co2+的定制苯胺蓝培养基(特努瓦公司(Teknova))中或在补充了2g/L合成完全氨基酸混合物(MP生物医疗公司(MP Biomedicals))、1％葡萄糖和5μg/ml氯霉素的戴维斯基本培养基(海美迪公司(HiMedia))中进行培养。使培养物在37℃下生长16小时。使用40μL的该培养物来接种2ml的新鲜培养基，并将所得的培养物在37℃下孵育至对数生长中期(600nm处的OD为约0.7)。然后将培养物用1mM IPTG诱导，并在37℃下继续孵育4小时或24℃下孵育20小时。
通过离心收获细胞，两次冷冻并解冻，并使用PeriPreps(PERIPREPS TM)完全裂解方案(埃皮中心公司(Epicentre))裂解。通过在对粗制裂解物进行离心后收集上清液级分来制备裂解物中的可溶性蛋白。
如上文实例2所述，通过聚丙烯酰胺凝胶电泳分析粗制和可溶性裂解物中的差向异构酶蛋白水平。
实例4.差向异构酶变体的生成
基于US 8,635,029中描述的方法，将编码氨基酸变异的核苷酸变化引入BMCGD1优化的编码序列中，并用于生成差向异构酶变体的编码序列。这些编码序列被工程化到pHT254(莫比技术公司(MoBiTech,Inc.))中。此载体从强Pgrac100启动子表达感兴趣的基因，该启动子衍生自枯草芽孢杆菌的groESL操纵子之前的启动子。它包含融合至lac操纵子的改良调控元件，允许被IPTG诱导并具有强核糖体结合位点。在groESL启动子的保守区(包括UP元件，-35和-15区)优化核苷酸(Phan等人，2012)。将各编码序列在BamHI和XmaI限制性位点克隆到表达载体pHT254中。
然后如上所述将载体转化到枯草芽孢杆菌DB1077菌株中。在含有5μg/mL氯霉素的LB琼脂培养基上选择转化子。
将九十六个枯草芽孢杆菌转化子选入戴维斯基本培养基。通过如下制备戴维斯基本培养基：使用试剂级水且终体积为1L，具有2克的合成完全氨基酸混合物(MP生物医疗公司，目录号4400-022)的10.6克有/无右旋糖的戴维斯基本肉汤培养基(海美迪公司，目录号M390-500G)，并在121℃下高压灭菌15分钟。使用前，添加葡萄糖至1％，并添加氯霉素至5μg/ml。
实例5.针对差向异构酶活性进行转化子筛选
为了进行D-果糖至D-阿洛酮糖差向异构酶筛选，将转化子选入补充了2g/L合成完全氨基酸(MP生物医疗公司)、1％葡萄糖和5μg/mL氯霉素的600μL戴维斯基本培养基(海美迪公司)。细胞在37℃下生长至对数中期，然后在24℃下用IPTG诱导20小时。通过离心收获细胞，并使用PeriPreps裂解方案(埃皮中心公司)裂解，终体积为75μL。通过在4％-12％Bis-Tris NuPAGE凝胶(英杰公司)上进行聚丙烯酰胺凝胶电泳来分析可溶性蛋白的表达，并根据定量标准通过密度测定法确定蛋白水平。回收的可溶性差向异构酶的范围为1-10μg/mL培养物。
关于枯草芽孢杆菌衍生的裂解物的差向异构酶活性，对100μL体积的反应进行了测定：10％v/v澄清的裂解物，低(200mM)或高(50％wt/wt)果糖和5mM MgCl2。将反应在70℃下孵育2小时，并通过添加10％体积的2％HCl并冷却至4℃来终止。在HPLC分析之前，将反应物通过截留分子量为10kDa的PES膜(颇尔公司(Pall))进行过滤。
结果在表3中示出。
表3.差向异构酶变体的表达和2小时果糖向阿洛酮糖转换概况
Figure BDA0002952303820000101
Figure BDA0002952303820000111
实例6.对野生型差向异构酶和具有一个、两个或三个氨基酸取代的差向异构酶变体的比较分析
在两种条件下(10％v/v澄清的裂解物，低(200mM)或高(50％wt/wt)果糖，50mMMES，pH 5.0和5mM MgCl2)对通过具有变体230338中的一个、两个或三个氨基酸取代(D89K、S154T和C167I)的差向异构酶变体而转换为阿洛酮糖的果糖的级分进行了测试，并与野生型差向异构酶进行了比较。结果显示在图1中，其中每对条形的左柱代表由200mM果糖开始1小时后果糖转换为阿洛酮糖的级分，每对条形的右柱代表由50％wt/wt果糖开始2小时后果糖转换为阿洛酮糖的级分。条形图上方的网格中显示了每种变体中存在的氨基酸取代，且这些变体的氨基酸序列在SEQ ID NO:16(变体230338)、SEQ ID NO:90(变体277285)、SEQID NO:92(变体277286)、SEQ ID NO:94(变体277287)、SEQ ID NO:96(变体277288)、SEQ IDNO:98(变体27289)和SEQ ID NO:100(变体27290)中提供。“204020”是野生型差向异构酶(SEQ ID NO:6)。差向异构酶表达(μg/ml)如图2所示。比活性(每μg/ml差向异构酶转换的果糖)如图3所示。
此实例表明，在评估酶的条件下，三重变体的催化活性最高。具有所有三个取代(D89K、S154T和C167I)的变体在200mM果糖和50％(w/w)果糖的情况下均具有最高的表达，并且是活性最高的酶。
参考文献
Baba et al.,“Construction of Escherichia coli K-12in-frame,single-gene knockout mutants:the Keio collection,”Molecular Systems Biology(2006)doi:10/1038/msb4100050,11pages
Chu et al.,“Expression,purification and activity of D-tagatose3-epimerase from Clostridium bolteae,”Shipin Gongye Keji 33,198-201,2012
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Woodyer&Armentrout,“Recombinant ketose 3-epimerases for conversion offructose to psicose,”WO 2014049373
Zhang et al.,“Characterization of a Metal-Dependent D-Psicose3-Epimerase from a Novel Strain,Desmospora sp.8437,J.Agricultural and FoodChemistry 61,11468-76,2013
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序列表
<110> 阿彻丹尼尔斯米德兰公司（Archer Daniels Midland Company）
<120> 差向异构酶及其用途
<130> 008200.00058
<140>
<141>
<150> US 62/716,204
<151> 2018-08-08
<160> 100
<170> 用于Windows的FastSEQ 4.0版
<210> 1
<211> 5120
<212> DNA
<213> 人工序列
<220>
<223> 盒
<400> 1
taagatgaaa aacgctgaca ttgactgggg acaggtcagt gaccagctag ataaagcgaa 60
agataagatt acgaaattca tagaatcaga tgaaggcaaa aacttcatcc agaaagtcat 120
tgatttcttc gtatctatct ggaatgcgat tgtatctata ttcaaataag aaaagcgccg 180
aaaaatcggc gtttctttta ttgctttaca cccgttttaa atggcagatc aagttttaca 240
atatcttcgt atgtttctcg cttcacgact aaatgagcct caccgttttc gacaaataca 300
acggcgggtc tcggaatacg gttataattg ttggccatgc tgtatccata agcgcctgta 360
caaaaaacgg caagaagatc gccttctttt acttccggca ggtcaatatc ccaaatcagc 420
atatctccgc tttcacagca ctttccggca attgataccg ttttgtcatg cgcttctccg 480
atcctgttgg ctgccgcagc ttcatattta gcttggtaaa gcgcaggacg aatattgtcg 540
ttcatgcctc cgtctacagc cacatattgg cggacacccg gcacttcttt ttgagagcca 600
accgtataaa gagttgtgcc tgcgtctccc acgagagaac ggcccggttc gatccaaatt 660
tccggaatgt caaaaccgta acgggaagca ttttctttca gcatgcttaa gttattggta 720
tgactggttt taagcgcaaa aaaagttgct ttttcgtacc tattaatgta tcgttttaga 780
aaaccgactg taaaaagtac agtcggcatt atctcatatt ataaaagcca gtcattaggc 840
ctatctgaca attcctgaat agagttcata aacaatcctg catgataacc atcacaaaca 900
gaatgatgta cctgtaaaga tagcggtaaa tatattgaat tacctttatt aatgaatttt 960
cctgctgtaa taatgggtag aaggtaatta ctattattat tgatatttaa gttaaaccca 1020
gtaaatgaag tccatggaat aatagaaaga gaaaaagcat tttcaggtat aggtgttttg 1080
ggaaacaatt tccccgaacc attatatttc tctacatcag aaaggtataa atcataaaac 1140
tctttgaagt cattctttac aggagtccaa ataccagaga atgttttaga tacaccatca 1200
aaaattgtat aaagtggctc taacttatcc caataaccta actctccgtc gctattgtaa 1260
ccagttctaa aagctgtatt tgagtttatc acccttgtca ctaagaaaat aaatgcaggg 1320
taaaatttat atccttcttg ttttatgttt cggtataaaa cactaatatc aatttctgtg 1380
gttatactaa aagtcgtttg ttggttcaaa taatgattaa atatctcttt tctcttccaa 1440
ttgtctaaat caattttatt aaagttcatt tgatatgcct cctaaatttt tatctaaagt 1500
gaatttagga ggcttacttg tctgctttct tcattagaat caatcctttt ttaaaagtca 1560
atattactgt aacataaata tatattttaa aaatatccca ctttatccaa ttttcgtttg 1620
ttgaactaat gggtgcttta gttgaagaat aaagaccaca ttaaaaaatg tggtcttttg 1680
tgttttttta aaggatttga gcgtagcgaa aaatcctttt ctttcttatc ttgataataa 1740
gggtaactat tgccgatcgt ccattccgac agcatcgcca gtcactatgg cgtgctgcta 1800
gcgccattcg ccattcaggc tgcgcaactg ttgggaaggg cgatcggtgc gggcctcttc 1860
gctattacgc cagctggcga aagggggatg tgctgcaagg cgattaagtt gggtaacgcc 1920
agggttttcc cagtcacgac gttgtaaaac gacggccagt gaattcgagc tcaggcctta 1980
actcacatta attgcgttgc gctcactgcc cgctttccag tcgggaaacc tgtcgtgcca 2040
gctgcattaa tgaatcggcc aacgcgcggg gagaggcggt ttgcgtattg ggcgccaggg 2100
tggtttttct tttcaccagt gagacgggca acagctgatt gcccttcacc gcctggccct 2160
gagagagttg cagcaagcgg tccacgctgg tttgccccag caggcgaaaa tcctgtttga 2220
tggtggttga cggcgggata taacatgagc tgtcttcggt atcgtcgtat cccactaccg 2280
agatatccgc accaacgcgc agcccggact cggtaatggc gcgcattgcg cccagcgcca 2340
tctgatcgtt ggcaaccagc atcgcagtgg gaacgatgcc ctcattcagc atttgcatgg 2400
tttgttgaaa accggacatg gcactccagt cgccttcccg ttccgctatc ggctgaattt 2460
gattgcgagt gagatattta tgccagccag ccagacgcag acgcgccgag acagaactta 2520
atgggcccgc taacagcgcg atttgctggt gacccaatgc gaccagatgc tccacgccca 2580
gtcgcgtacc gtcttcatgg gagaaaataa tactgttgat gggtgtctgg tcagagacat 2640
caagaaataa cgccggaaca ttagtgcagg cagcttccac agcaatggca tcctggtcat 2700
ccagcggata gttaatgatc agcccactga cgcgttgcgc gagaagattg tgcaccgccg 2760
ctttacaggc ttcgacgccg cttcgttcta ccatcgacac caccacgctg gcacccagtt 2820
gatcggcgcg agatttaatc gccgcgacaa tttgcgacgg cgcgtgcagg gccagactgg 2880
aggtggcaac gccaatcagc aacgactgtt tgcccgccag ttgttgtgcc acgcggttgg 2940
gaatgtaatt cagctccgcc atcgccgctt ccactttttc ccgcgttttc gcagaaacgt 3000
ggctggcctg gttcaccacg cgggaaacgg tctgataaga gacaccggca tactctgcga 3060
catcgtataa cgttactggt ttcatcaaaa tcgtctccct ccgtttgaat atttgattga 3120
tcgtaaccag atgaagcact ctttccacta tccctacagt gttatggctt gaacaatcac 3180
gaaacaataa ttggtacgta cgatctttca gccgactcaa acatcaaatc ttacaaatgt 3240
agtctttgaa agtattacat atgtaagatt taaatgcaac cgttttttcg gaaggaaatg 3300
atgacctcgt ttccaccgga attagcttgg taccaaagga ggtaaggatc actagaaaat 3360
tttttaaaaa atctcttgac attggaaggg agatatgtta ttataagaat tgcggaattg 3420
tgagcggata acaattccca tataaaggag gaaggatcca tgaataagtt aggtgtgcac 3480
gcattagttt gggaagcggg ttggagtcgt gatgagtgtg ctcgtgccat cgcacgcacc 3540
gcggaaacgg gatttgactt cattgaagtc ccagcgttag atccggcaag cattgatgca 3600
gagtttactc gcagagagtt agaacgccat gggttgggag taaccttttc gcttggactc 3660
gatgcgcaaa cagacattag ttctggtgat ccggaacgcg cagcgcgggg taaagctaaa 3720
ttagacgatg tcttacgtgt agcccgggat tgtggagcga ctcatgtctg tggaattctc 3780
tatagtgcat ttcaaaaaaa tgcagttcct acgacccgtg cgggtgtcgc catggccgcg 3840
gacattttag gacaggtagc tgatactgca gcacaatacg gtattacttt ggggttagaa 3900
gtcgttaacc gttatgagtc aaatgtattg aacaccgcgt cacagggtgt tgaactttgc 3960
gagcgtattg gtcgtcccaa cgtaaaagtg catttagata cgtatcacat gaatattgaa 4020
gagagcgata ttatgagcgc gatcagagat acgggagaca ggctagggta tttccatatt 4080
ggcgattctc atcgtggtta cctgggttcc ggaaacgtcg actttactgc cgtatttagg 4140
gcgctggtat tttctggata tacgggaccg attacatttg agtcattctc cagtagagtc 4200
gtaggacaac cattagaggg aattctggca atttggcgta atttatggga agattcccgc 4260
gatctagcta gtcacgcctt agcatatact cgtgtccagt taaaatctgc tcaagaagcc 4320
ctaaaacaag ccgagcgcag tcgcttaccg tgataacccg ggcagcccgc ctaatgagcg 4380
ggcttttttc acgtcacgcg tccatggaga tctaagcttt cactttttgc ttcagggttt 4440
cagccgtatg gtgatcgagt tcgcctgtta atcgaataca aagcacagat tctttgacat 4500
tcatgtcaat tccaaggctc atgctcattc ctccttgata tgatcggata atgagtgttt 4560
cgatttcgac ggaatgaatt ccttcaccgt gacaaaacta gtggtcattc ggcataatta 4620
cttaaatttt gtccagtctc ccatcgtccg ctttaagaat gtgataaacc cggctttctt 4680
catatcttct tttgcagcaa caggactttc agcgagtact tctccatcct ttttcagaac 4740
aagagtgcca agctcttggc ctttttgaat cggagcacta atattgtcct tcatcttgat 4800
ttcttttttc acatcgttca tatcctcgcc ttttttcgtc aatattgaaa tcggctcaga 4860
tgtagtgagt tcgataaatt tttgtttccc ttttttgacc tttacttttg ctactgtttg 4920
atttcgttta tataaaggat gcgtttcata ttggctaaag gcgaagtcaa gcatttttgt 4980
cacttgcgcg tttctttctt taggcgtgct cgctccgaat acaaccgcta tggcccgcat 5040
gtttcctttt ttagccgaag cagtcagaca atatttcgct tcgcctgtat agcctgtttt 5100
tacgccgtct acaccaggat 5120
<210> 2
<211> 1925
<212> DNA
<213> 人工序列
<220>
<223> 盒
<400> 2
ttattgcttt acacccgttt taaatggcag atcaagtttt acaatatctt cgtatgtttc 60
tcgcttcacg actaaatgag cctcaccgtt ttcgacaaat acaacggcgg gtctcggaat 120
acggttataa ttgttggcca tgctgtatcc ataagcgcct gtacaaaaaa cggcaagaag 180
atcgccttct tttacttccg gcaggtcaat atcccaaatc agcatatctc cgctttcaca 240
gcactttccg gcaattgata ccgttttgtc atgcgcttct ccgatcctgt tggctgccgc 300
agcttcatat ttagcttggt aaagcgcagg acgaatattg tcgttcatgc ctccgtctac 360
agccacatat tggcggacac ccggcacttc tttttgagag ccaaccgtat aaagagttgt 420
gcctgcgtct cccacgagag aacggcccgg ttcgatccaa atttccggaa tgtcaaaacc 480
gtaacgggaa gcattttctt tcacagcttc gataattttt tcaacgtatt cagtggcatg 540
aagcggttca tcatcttccg tataacgaat gccgaaacct cctccaagat tcagcacctt 600
ggatacaaat gaatatgaat ctctccattc gtctagtttt ttgaagattt tttccgctgc 660
taacacaaaa ccggccgtat caaagatttg cgagccgata tggcaatgga cacccagcag 720
ctgaatgtgt tccgattgta atacttgttc aatggcccgt tcagtttgtc cgttatgaag 780
atcgaaacca aactttgaat cttcctggcc cgttgtaatg tagtcatgcg tatgcgcttc 840
tactccgggc gtgatccgaa gaagaacatc gatggagtga cccgtttctt tacataggtc 900
ttcaagaagc gcgatttcat agaaattatc caccacaatg cagccgatgc ggtgctcaag 960
cgccatccgc agttcttccc tgctcttatt gtttccatga aagtggatgc gttctgccgg 1020
aaagcctgct gcaacagccg tatatagctc tcctccggat acgacatcta aagaaagtcc 1080
ctcttcctca gcgagctgaa tcattgcgac tgatgagaat gctttgctcg catatgccac 1140
ctgtgctttc agccctgcag aaataaacgc ctgcttaaag cttttagcac gctcacgtat 1200
taaagccaca tcatatacgt aaagaggtgt accatatttc tccgctaaat agagagcatc 1260
cacacctccg atttctaaat gaccatgttg attttgtctg cttgtgccgt gtaagaacaa 1320
tgtcattccc tctttctccg cttatggatg aaaggacagt tttatggact gtcccttcat 1380
aattaagaca tacattatca tactcttcag tcagtttcaa tgcgatcact gcccgctttc 1440
cagtcgggaa acctgtcgtg ccagctgcat taatgaatcg gccaacgcgc ggggagaggc 1500
ggtttgcgta ttgggcgcca gggtggtttt tcttttcacc agtgagacgg gcaacagctg 1560
attgcccttc accgcctggc cctgagagag ttgcagcaag cggtccacgc tggtttgccc 1620
cagcaggcga aaatcctgtt tgatggtggt tgacggcggg atataacatg agctgtcttc 1680
ggtatcgtcg tatcccacta ccgagatatc cgcaccaacg cgcagcccgg actcggtaat 1740
ggcgcgcatt gcgcccagcg ccatctgatc gttggcaacc agcatcgcag tgggaacgat 1800
gccctcattc agcatttgca tggtttgttg aaaaccggac atggcactcc agtcgccttc 1860
ccgttccgct atcggctgaa tttgattgcg agtgagatat ttatgccagc cagccagacg 1920
cagac 1925
<210> 3
<211> 27
<212> DNA
<213> 人工序列
<220>
<223> 引物
<400> 3
ttattgcttt acacccgttt taaatgg 27
<210> 4
<211> 25
<212> DNA
<213> 人工序列
<220>
<223> 引物
<400> 4
tctcactcgc aatcaaattc agccg 25
<210> 5
<211> 897
<212> DNA
<213> 人工序列
<220>
<223> 木糖异构酶的密码子优化序列
[多噬伯克霍尔德氏菌CGD1]
<400> 5
atgaataagt taggtgtgca cgcattagtt tgggaagcgg gttggagtcg tgatgagtgt 60
gctcgtgcca tcgcacgcac cgcggaaacg ggatttgact tcattgaagt cccagcgtta 120
gatccggcaa gcattgatgc agagtttact cgcagagagt tagaacgcca tgggttggga 180
gtaacctttt cgcttggact cgatgcgcaa acagacatta gttctggtga tccggaacgc 240
gcagcgcggg gtaaagctaa attagacgat gtcttacgtg tagcccggga ttgtggagcg 300
actcatgtct gtggaattct ctatagtgca tttcaaaaaa atgcagttcc tacgacccgt 360
gcgggtgtcg ccatggccgc ggacatttta ggacaggtag ctgatactgc agcacaatac 420
ggtattactt tggggttaga agtcgttaac cgttatgagt caaatgtatt gaacaccgcg 480
tcacagggtg ttgaactttg cgagcgtatt ggtcgtccca acgtaaaagt gcatttagat 540
acgtatcaca tgaatattga agagagcgat attatgagcg cgatcagaga tacgggagac 600
aggctagggt atttccatat tggcgattct catcgtggtt acctgggttc cggaaacgtc 660
gactttactg ccgtatttag ggcgctggta ttttctggat atacgggacc gattacattt 720
gagtcattct ccagtagagt cgtaggacaa ccattagagg gaattctggc aatttggcgt 780
aatttatggg aagattcccg cgatctagct agtcacgcct tagcatatac tcgtgtccag 840
ttaaaatctg ctcaagaagc cctaaaacaa gccgagcgca gtcgcttacc gtgataa 897
<210> 6
<211> 297
<212> PRT
<213> 多噬伯克霍尔德氏菌
<400> 6
Met Asn Lys Leu Gly Val His Ala Leu Val Trp Glu Ala Gly Trp Ser
1 5 10 15
Arg Asp Glu Cys Ala Arg Ala Ile Ala Arg Thr Ala Glu Thr Gly Phe
20 25 30
Asp Phe Ile Glu Val Pro Ala Leu Asp Pro Ala Ser Ile Asp Ala Glu
35 40 45
Phe Thr Arg Arg Glu Leu Glu Arg His Gly Leu Gly Val Thr Phe Ser
50 55 60
Leu Gly Leu Asp Ala Gln Thr Asp Ile Ser Ser Gly Asp Pro Glu Arg
65 70 75 80
Ala Ala Arg Gly Lys Ala Lys Leu Asp Asp Val Leu Arg Val Ala Arg
85 90 95
Asp Cys Gly Ala Thr His Val Cys Gly Ile Leu Tyr Ser Ala Phe Gln
100 105 110
Lys Asn Ala Val Pro Thr Thr Arg Ala Gly Val Ala Met Ala Ala Asp
115 120 125
Ile Leu Gly Gln Val Ala Asp Thr Ala Ala Gln Tyr Gly Ile Thr Leu
130 135 140
Gly Leu Glu Val Val Asn Arg Tyr Glu Ser Asn Val Leu Asn Thr Ala
145 150 155 160
Ser Gln Gly Val Glu Leu Cys Glu Arg Ile Gly Arg Pro Asn Val Lys
165 170 175
Val His Leu Asp Thr Tyr His Met Asn Ile Glu Glu Ser Asp Ile Met
180 185 190
Ser Ala Ile Arg Asp Thr Gly Asp Arg Leu Gly Tyr Phe His Ile Gly
195 200 205
Asp Ser His Arg Gly Tyr Leu Gly Ser Gly Asn Val Asp Phe Thr Ala
210 215 220
Val Phe Arg Ala Leu Val Phe Ser Gly Tyr Thr Gly Pro Ile Thr Phe
225 230 235 240
Glu Ser Phe Ser Ser Arg Val Val Gly Gln Pro Leu Glu Gly Ile Leu
245 250 255
Ala Ile Trp Arg Asn Leu Trp Glu Asp Ser Arg Asp Leu Ala Ser His
260 265 270
Ala Leu Ala Tyr Thr Arg Val Gln Leu Lys Ser Ala Gln Glu Ala Leu
275 280 285
Lys Gln Ala Glu Arg Ser Arg Leu Pro
290 295
<210> 7
<211> 897
<212> DNA
<213> 人工序列
<220>
<223> 变体230323的编码序列
<400> 7
atgaataagt taggtgtgca cgcattagtt tgggaagcgg gttggagtcg tgatgagtgt 60
gctcgtgcca tcgcacgcac cgcggaaacg ggatttgact tcattgaaat tccagcgtta 120
gatccggcaa gcattgatgc agagtttact cgcagagagt tagaacgcca tgggttggga 180
gtaacctttt cgcttggact cgatgcgcaa acagacatta gttctggtga tccggaacgc 240
gcagcggcag gtaaagctaa attagacgat gtcttacgtg tagcccggga ttgtggagcg 300
actcatgtct gtggaattct ctatagtgca tttcaaaaaa atgcagttcc tacgacccgt 360
gcgggtgtcg ccatggccgc ggacatttta ggacaggtag ctgatactgc agcacaatac 420
ggtattactt tggggttaga agtcgttaac cgttatgaga caaatgtatt gaacaccgcg 480
tcacagggtg ttgaactttg cgagcgtatt ggtcgtccca acgtaaaagt gcatttagat 540
acgtatcaca tgaatattga agagagcgat attatgagcg cgatcagaga tacgggagac 600
aggctagggt atttccatat tggcgattct catcgtggtt acctgggttc cggaaacgtc 660
gactttactg ccgtatttag ggcgctggta ttttctggat atacgggacc gattacattt 720
gagtcattct ccagtagagt cgtaggacaa ccattagagg gaattctggc aatttggcgt 780
aatttatggg aagattcccg cgatctagct agtcacgcct tagcatatac tcgtgtccag 840
ttaaaatctg ctcaagaagc cctaaaacaa gccgagcgca gtcgcttacc gtgataa 897
<210> 8
<211> 297
<212> PRT
<213> 人工序列
<220>
<223> 变体230323
<400> 8
Met Asn Lys Leu Gly Val His Ala Leu Val Trp Glu Ala Gly Trp Ser
1 5 10 15
Arg Asp Glu Cys Ala Arg Ala Ile Ala Arg Thr Ala Glu Thr Gly Phe
20 25 30
Asp Phe Ile Glu Ile Pro Ala Leu Asp Pro Ala Ser Ile Asp Ala Glu
35 40 45
Phe Thr Arg Arg Glu Leu Glu Arg His Gly Leu Gly Val Thr Phe Ser
50 55 60
Leu Gly Leu Asp Ala Gln Thr Asp Ile Ser Ser Gly Asp Pro Glu Arg
65 70 75 80
Ala Ala Arg Gly Lys Ala Lys Leu Asp Asp Val Leu Arg Val Ala Arg
85 90 95
Asp Cys Gly Ala Thr His Val Cys Gly Ile Leu Tyr Ser Ala Phe Gln
100 105 110
Lys Asn Ala Val Pro Thr Thr Arg Ala Gly Val Ala Met Ala Ala Asp
115 120 125
Ile Leu Gly Gln Val Ala Asp His Ala Ala Gln Tyr Gly Ile Thr Leu
130 135 140
Gly Leu Glu Val Val Asn Arg Tyr Glu Ser Asn Val Leu Asn Thr Ala
145 150 155 160
Ser Gln Gly Val Glu Leu Cys Glu Arg Ile Gly Arg Pro Asn Val Lys
165 170 175
Val His Leu Asp Thr Tyr His Met Asn Ile Glu Glu Ser Asp Ile Met
180 185 190
Ser Ala Ile Arg Asp Thr Gly Asp Arg Leu Gly Tyr Phe His Ile Gly
195 200 205
Asp Ser Asn Arg Gly Tyr Leu Gly Ser Gly Asn Val Asp Phe Thr Ala
210 215 220
Val Phe Arg Ala Leu Val Phe Ser Gly Tyr Thr Gly Pro Ile Thr Phe
225 230 235 240
Glu Ser Phe Ser Ser Arg Val Val Gly Gln Pro Leu Glu Gly Ile Leu
245 250 255
Ala Ile Trp Arg Asn Leu Trp Glu Asp Ser Arg Asp Leu Ala Ser His
260 265 270
Ala Leu Ala Tyr Thr Arg Val Gln Leu Lys Ser Ala Gln Glu Ala Leu
275 280 285
Lys Gln Ala Glu Arg Ser Arg Leu Pro
290 295
<210> 9
<211> 897
<212> DNA
<213> 人工序列
<220>
<223> 变体230329的编码序列
<400> 9
atgaataagt taggtgtgca cgcattagtt tgggaagcgg gttggagtcg tgatgagtgt 60
gctcgtgcca tcgcacgcac cgcggaaacg ggatttgact tcattgaaat tccagcgtta 120
gatccggcaa gcattgatgc agagtttact cgcagagagt tagaacgcca tgggttggga 180
gtaacctttt cgcttggact cgatgcgcaa acagacatta gttctggtga tccggaacgc 240
gcagcgcggg gtaaagctaa attagacgat gtcttacgtg tagcccggga ttgtggagcg 300
actcatgtct gtggaattct ctatagtgca tttcaaaaaa atgcagttcc tacgacccgt 360
gcgggtgtcg ccatggccgc ggacatttta ggacaggtag ctgatactgc agcacaatac 420
ggtattactt tggggttaga agtcgttaac cgttatgaga caaatgtatt gaacaccgcg 480
tcacagggtg ttgaacttat tgagcgtatt ggtcgtccca acgtaaaagt gcatttagat 540
acgtatcaca tgaatattga agagagcgat attatgagcg cgatcagaga tacgggagac 600
aggctagggt atttccatat tggcgattct catcgtggtt acctgggttc cggaaacgtc 660
gactttactg ccgtatttag ggcgctggta ttttctggat atacgggacc gattacattt 720
gagtcattct ccagtagagt cgtaggacaa ccattagagg gaattctggc aatttggcgt 780
aatttatggg aagattcccg cgatctagct agtcacgcct tagcatatac tcgtgtccag 840
ttaaaatctg ctcaagaagc cctaaaacaa gccgagcgca gtcgcttacc gtgataa 897
<210> 10
<211> 297
<212> PRT
<213> 人工序列
<220>
<223> 变体230329
<400> 10
Met Asn Lys Leu Gly Val His Ala Leu Val Trp Glu Ala Gly Trp Ser
1 5 10 15
Arg Asp Glu Cys Ala Arg Ala Ile Ala Arg Thr Ala Glu Thr Gly Phe
20 25 30
Asp Phe Ile Glu Val Pro Ala Leu Asp Pro Ala Ser Ile Asp Ala Glu
35 40 45
Phe Thr Arg Arg Glu Leu Glu Arg His Gly Leu Gly Val Thr Phe Ser
50 55 60
Leu Gly Leu Asp Ala Gln Thr Asp Ile Ser Ser Gly Asp Pro Glu Arg
65 70 75 80
Ala Ala Arg Gly Lys Ala Lys Leu Asp Asp Val Leu Arg Val Ala Arg
85 90 95
Asp Cys Gly Ala Thr His Val Ala Gly Ile Leu Tyr Ser Ala Phe Gln
100 105 110
Lys Asn Ala Val Pro Thr Thr Arg Ala Gly Val Ala Met Ala Ala Asp
115 120 125
Ile Leu Gly Gln Val Ala Asp Thr Ala Ala Gln Tyr Gly Ile Thr Leu
130 135 140
Gly Leu Glu Val Val Asn Arg Tyr Glu Ser His Val Leu Asn Thr Ala
145 150 155 160
Ser Gln Gly Val Glu Leu Cys Glu Arg Ile Gly Arg Pro Asn Val Lys
165 170 175
Val His Leu Asp Thr Tyr His Met Asn Ile Glu Glu Ser Asp Ile Met
180 185 190
Ser Ala Ile Arg Asp Thr Gly Asp Arg Leu Gly Tyr Phe His Ile Gly
195 200 205
Asp Ser His Arg Gly Tyr Leu Gly Ser Gly Asn Val Asp Phe Thr Ala
210 215 220
Val Phe Arg Ala Leu Ala Phe Ser Gly Tyr Thr Gly Pro Ile Thr Phe
225 230 235 240
Glu Ser Phe Ser Ser Arg Val Val Gly Gln Pro Leu Glu Gly Ile Leu
245 250 255
Ala Ile Trp Arg Asn Leu Trp Glu Asp Ser Arg Asp Leu Ala Ser His
260 265 270
Ala Leu Ala Tyr Thr Arg Val Gln Leu Lys Ser Ala Gln Glu Ala Leu
275 280 285
Lys Gln Ala Glu Arg Ser Arg Leu Pro
290 295
<210> 11
<211> 897
<212> DNA
<213> 人工序列
<220>
<223> 变体230333的编码序列
<400> 11
atgaataagt taggtgtgca cgcattagtt tgggaagcgg gttggagtcg tgatgagtgt 60
gctcgtgcca tcgcacgcac cgcggaaacg ggatttgact tcattgaagt cccagcgtta 120
gatccggcaa gcattgatgc agagtttact cgcagagagt tagaacgcca tgggttggga 180
gtaacctttt cgcttggact cgatgcgcaa acagacatta gttctggtga tccggaacgc 240
gcagcggcag gtaaagctaa attaaaagat gtcttacgtg tagcccggga ttgtggagcg 300
actcatgtct gtggaattct ctatagtgca tttcaaaaaa atgcagttcc tacgacccgt 360
gcgggtgtcg ccatggccgc ggacatttta ggacaggtag ctgatactgc agcacaatac 420
ggtattactt tggggttaga agtcgttaac cgttatgagt caaatgtatt gaacaccgcg 480
tcacagggtg ttgaacttat tgagcgtatt ggtcgtccca acgtaaaagt gcatttagat 540
acgtatcaca tgaatattga agagagcgat attatgagcg cgatcagaga tacgggagac 600
aggctagggt atttccatat tggcgattct catcgtggtt acctgggttc cggaaacgtc 660
gactttactg ccgtatttag ggcgctggta ttttctggat atacgggacc gattacattt 720
gagtcattct ccagtagagt cgtaggacaa ccattagagg gaattctggc aatttggcgt 780
aatttatggg aagattcccg cgatctagct agtcacgcct tagcatatac tcgtgtccag 840
ttaaaatctg ctcaagaagc cctaaaacaa gccgagcgca gtcgcttacc gtgataa 897
<210> 12
<211> 297
<212> PRT
<213> 人工序列
<220>
<223> 变体230333
<400> 12
Met Asn Lys Phe Gly Val His Ala Leu Val Trp Glu Ala Gly Trp Ser
1 5 10 15
Arg Asp Glu Cys Ala Arg Ala Ile Ala Arg Thr Ala Glu Thr Gly Phe
20 25 30
Asp Phe Ile Glu Val Pro Ala Leu Asp Pro Ala Ser Ile Asp Ala Glu
35 40 45
Phe Thr Arg Arg Glu Leu Glu Arg His Gly Leu Gly Val Thr Phe Ser
50 55 60
Leu Gly Leu Asp Ala Gln Thr Asp Ile Ser Ser Gly Asp Pro Glu Arg
65 70 75 80
Ala Ala Arg Gly Lys Ala Lys Leu Asp Asp Val Leu Arg Val Ala Arg
85 90 95
Asp Cys Gly Ala Thr His Val Cys Gly Ile Leu Tyr Ser Ala Phe Gln
100 105 110
Lys Asn Ala Val Pro Thr Thr Arg Ala Gly Val Ala Met Ala Ala Asp
115 120 125
Ile Leu Gly Gln Val Ala Asp Thr Ala Ala Gln Tyr Gly Ile Thr Leu
130 135 140
Gly Leu Glu Val Val Asn Arg Tyr Glu Ser Asn Val Leu Asn Thr Ala
145 150 155 160
Ser Gln Gly Val Glu Leu Cys Glu Arg Ile Gly Arg Pro Asn Val Lys
165 170 175
Leu His Leu Asp Thr Tyr His Met Asn Ile Glu Glu Ser Asp Ile Met
180 185 190
Ser Ala Ile Arg Asp Thr Gly Asp Arg Leu Gly Tyr Phe His Ile Gly
195 200 205
Asp Ser His Arg Gly Tyr Leu Gly Ser Gly Asn Val Asp Phe Thr Ala
210 215 220
Val Phe Arg Ala Leu Val Phe Ser Gly Tyr Thr Gly Pro Ile Thr Phe
225 230 235 240
Glu Pro Phe Ser Ser Arg Val Val Gly Gln Pro Leu Glu Gly Ile Leu
245 250 255
Ala Ile Trp Arg Asn Leu Trp Glu Asp Ser Arg Asp Leu Ala Ser His
260 265 270
Ala Leu Ala Tyr Thr Arg Val Gln Leu Lys Ser Ala Gln Glu Ala Leu
275 280 285
Lys Gln Ala Glu Arg Ser Arg Leu Pro
290 295
<210> 13
<211> 897
<212> DNA
<213> 人工序列
<220>
<223> 变体230335的编码序列
<400> 13
atgaataagt taggtgtgca cgcattagtt tgggaagcgg gttggagtcg tgatgagtgt 60
gctcgtgcca tcgcacgcac cgcggaaacg ggatttgact tcattgaagt cccagcgtta 120
gatccggcaa gcattgatgc agagtttact cgcagagagt tagaacgcca tgggttggga 180
gtaacctttt cgcttggact cgatgcgcaa acagacatta gttctggtga tccggaacgc 240
gcagcggcag gtaaagctaa attagacgat gtcttacgtg tagcccggga ttgtggagcg 300
actcatgtct gtggaattct ctatagtgca tttcaaaaaa atgcagttcc tacgacccgt 360
gcgggtgtcg ccatggccgc ggacatttta ggacaggtag ctgatactgc agcacaatac 420
ggtattactt tggggttaga agtcgttaac cgttatgaga caaatgtatt gaacaccgcg 480
tcacagggtg ttgaacttat tgagcgtatt ggtcgtccca acgtaaaagt gcatttagat 540
acgtatcaca tgaatattga agagagcgat attatgagcg cgatcagaga tacgggagac 600
aggctagggt atttccatat tggcgattct catcgtggtt acctgggttc cggaaacgtc 660
gactttactg ccgtatttag ggcgctggta ttttctggat atacgggacc gattacattt 720
gagtcattct ccagtagagt cgtaggacaa ccattagagg gaattctggc aatttggcgt 780
aatttatggg aagattcccg cgatctagct agtcacgcct tagcatatac tcgtgtccag 840
ttaaaatctg ctcaagaagc cctaaaacaa gccgagcgca gtcgcttacc gtgataa 897
<210> 14
<211> 297
<212> PRT
<213> 人工序列
<220>
<223> 变体230335
<400> 14
Met Asn Lys Leu Gly Val His Ala Leu Val Trp Glu Ala Gly Trp Ser
1 5 10 15
Arg Asp Glu Cys Ala Arg Ala Ile Ala Arg Thr Ala Glu Thr Gly Phe
20 25 30
Asp Phe Val Glu Val Pro Ala Leu Asp Pro Ala Ser Ile Asp Ala Glu
35 40 45
Phe Thr Arg Arg Glu Leu Glu Arg His Gly Leu Gly Val Thr Phe Ser
50 55 60
Leu Gly Leu Asp Ala Gln Thr Asp Ile Ser Ser Gly Asp Pro Glu Arg
65 70 75 80
Ala Ala Arg Gly Lys Ala Lys Leu Asp Asp Val Leu Arg Val Ala Arg
85 90 95
Asp Cys Gly Ala Thr His Val Cys Gly Ile Leu Tyr Ser Ala Phe Gln
100 105 110
Lys Asn Ala Val Pro Thr Thr Arg Ala Gly Val Ala Met Ala Ala Asp
115 120 125
Ile Leu Gly Gln Val Ala Asp Thr Ala Glu Gln Tyr Gly Ile Thr Leu
130 135 140
Gly Leu Glu Val Val Asn Arg Tyr Glu Ser Asn Val Leu Asn Thr Ala
145 150 155 160
Ser Gln Gly Val Glu Leu Cys Glu Arg Ile Gly Arg Pro Asn Val Lys
165 170 175
Val His Leu Asp Thr Tyr His Met Asn Ile Glu Glu Ser Asp Ile Met
180 185 190
Ser Ala Ile Arg Asp Thr Gly Asp Arg Leu Gly Tyr Phe His Ile Gly
195 200 205
Asp Ser His Arg Gly Tyr Leu Gly Ser Gly Asn Leu Asp Phe Thr Ala
210 215 220
Val Phe Arg Ala Leu Val Phe Ser Gly Tyr Thr Gly Pro Ile Thr Phe
225 230 235 240
Glu Ser Phe Ser Ser Arg Val Val Gly Gln Pro Leu Glu Gly Ile Leu
245 250 255
Ala Ile Trp Arg Asn Leu Trp Glu Asp Ser Arg Asp Leu Ala Ser His
260 265 270
Ala Leu Ala Tyr Thr Arg Val Gln Leu Lys Ser Ala Gln Glu Ala Leu
275 280 285
Lys Gln Ala Glu Arg Ser Arg Leu Pro
290 295
<210> 15
<211> 897
<212> DNA
<213> 人工序列
<220>
<223> 变体230338的编码序列
<400> 15
atgaataagt taggtgtgca cgcattagtt tgggaagcgg gttggagtcg tgatgagtgt 60
gctcgtgcca tcgcacgcac cgcggaaacg ggatttgact tcattgaagt cccagcgtta 120
gatccggcaa gcattgatgc agagtttact cgcagagagt tagaacgcca tgggttggga 180
gtaacctttt cgcttggact cgatgcgcaa acagacatta gttctggtga tccggaacgc 240
gcagcgcggg gtaaagctaa attaaaagat gtcttacgtg tagcccggga ttgtggagcg 300
actcatgtct gtggaattct ctatagtgca tttcaaaaaa atgcagttcc tacgacccgt 360
gcgggtgtcg ccatggccgc ggacatttta ggacaggtag ctgatactgc agcacaatac 420
ggtattactt tggggttaga agtcgttaac cgttatgaga caaatgtatt gaacaccgcg 480
tcacagggtg ttgaacttat tgagcgtatt ggtcgtccca acgtaaaagt gcatttagat 540
acgtatcaca tgaatattga agagagcgat attatgagcg cgatcagaga tacgggagac 600
aggctagggt atttccatat tggcgattct catcgtggtt acctgggttc cggaaacgtc 660
gactttactg ccgtatttag ggcgctggta ttttctggat atacgggacc gattacattt 720
gagtcattct ccagtagagt cgtaggacaa ccattagagg gaattctggc aatttggcgt 780
aatttatggg aagattcccg cgatctagct agtcacgcct tagcatatac tcgtgtccag 840
ttaaaatctg ctcaagaagc cctaaaacaa gccgagcgca gtcgcttacc gtgataa 897
<210> 16
<211> 297
<212> PRT
<213> 人工序列
<220>
<223> 变体230338
<400> 16
Met Asn Lys Leu Gly Val His Ala Leu Val Trp Glu Ala Gly Trp Ser
1 5 10 15
Arg Asp Glu Cys Ala Arg Ala Ile Ala Arg Thr Ala Glu Thr Gly Phe
20 25 30
Asp Phe Ile Glu Val Pro Ala Leu Asp Pro Ala Ser Ile Asp Ala Glu
35 40 45
Phe Thr Arg Arg Glu Leu Glu Arg His Gly Leu Gly Val Thr Phe Ser
50 55 60
Leu Gly Leu Asp Ala Gln Thr Asp Ile Ser Ser Gly Asp Pro Glu Arg
65 70 75 80
Ala Ala Arg Gly Lys Ala Lys Leu Asp Asp Val Leu Arg Val Ala Arg
85 90 95
Asp Cys Gly Gly Thr His Val Cys Gly Ile Leu Tyr Ser Ala Phe Gln
100 105 110
Lys Asn Ala Val Pro Thr Thr Arg Ala Gly Val Ala Met Ala Ala Asp
115 120 125
Ile Leu Gly Gln Val Ala Asp Thr Ala Ala Gln Tyr Gly Ile Thr Leu
130 135 140
Gly Leu Glu Val Val Asn Arg Tyr Glu Ser Asn Leu Leu Asn Thr Ala
145 150 155 160
Ser Gln Gly Val Glu Leu Cys Glu Arg Ile Gly Arg Pro Asn Val Lys
165 170 175
Val His Leu Asp Thr Tyr His Met Asn Ile Glu Glu Ser Asp Ile Met
180 185 190
Ser Ala Ile Arg Asp Thr Gly Asp Arg Leu Gly Tyr Phe His Ile Gly
195 200 205
Asp Ser His Arg Gly Tyr Leu Gly Ser Gly Asn Val Asp Phe Thr Ala
210 215 220
Ile Phe Arg Ala Leu Val Phe Ser Gly Tyr Thr Gly Pro Ile Thr Phe
225 230 235 240
Glu Ser Phe Ser Ser Arg Val Val Gly Gln Pro Leu Glu Gly Ile Leu
245 250 255
Ala Ile Trp Arg Asn Leu Trp Glu Asp Ser Arg Asp Leu Ala Ser His
260 265 270
Ala Leu Ala Tyr Thr Arg Val Gln Leu Lys Ser Ala Gln Glu Ala Leu
275 280 285
Lys Gln Ala Glu Arg Ser Arg Leu Pro
290 295
<210> 17
<211> 897
<212> DNA
<213> 人工序列
<220>
<223> 变体256407的编码序列
<400> 17
atgaataagt taggtgtgca cgcattagtt tgggaagcgg gttggagtcg tgatgagtgt 60
gctcgtgcca tcgcacgcac cgcggaaacg ggatttgact tcattgaagt cccagcgtta 120
gatccggcaa gcattgatgc agagtttact cgcagagagt tagaacgcca tgggttggga 180
gtaacctttt cgcttggact cgatgcgcaa acagacatta gttctggtga tccggaacgc 240
gcagcgcggg gtaaagctaa attaaaagat gtcttacgtg tagcccggga ttgtggagcg 300
actcatgtct gtggaattct ctatagtgca ctgcaaaaat atgcagttcc tacgaccgca 360
gatggtgtcg ccatggccgc ggacatttta ggacaggtag ctgatactgc agcacaatac 420
ggtattactt tggggttaga agtcgttaac cgttatgaga caaatgtatt gaacaccgcg 480
tcacagggtg ttgaacttat tgagcgtatt ggtcgtccca acgtaaaagt gcatttagat 540
acgtatcaca tgaatattga agagagcgat attatgagcg cgatcagaga tacgggagac 600
aggctagggt atttccatat tggcgattct catcgtggtt acctgggttc cggaaacgtc 660
gactttactg ccgtatttag ggcgctggta ttttctggat atacgggacc gattacattt 720
gagtcattct ccagtagagt cgtaggacaa ccattagagg gaattctggc aatttggcgt 780
aatttatggg aagattcccg cgatctagct agtcacgcct tagcatatac tcgtgtccag 840
ttaaaatctg ctcaagaagc cctaaaacaa gccgagcgca gtcgcttacc gtgataa 897
<210> 18
<211> 297
<212> PRT
<213> 人工序列
<220>
<223> 变体256407
<400> 18
Met Asn Lys Leu Gly Val His Ala Leu Val Trp Glu Ala Gly Trp Ser
1 5 10 15
Arg Asp Glu Cys Ala Arg Ala Ile Ala Arg Thr Ala Glu Thr Gly Phe
20 25 30
Asp Phe Ile Glu Val Pro Ala Leu Asp Pro Ala Ser Ile Asp Ala Glu
35 40 45
Phe Thr Arg Arg Glu Leu Glu Arg His Gly Leu Gly Val Thr Phe Ser
50 55 60
Leu Gly Leu Asp Ala Gln Thr Asp Ile Ser Ser Gly Asp Pro Glu Arg
65 70 75 80
Ala Ala Arg Gly Lys Ala Lys Leu Lys Asp Val Leu Arg Val Ala Arg
85 90 95
Asp Cys Gly Ala Thr His Val Cys Gly Ile Leu Tyr Ser Ala Leu Gln
100 105 110
Lys Tyr Ala Val Pro Thr Thr Ala Asp Gly Val Ala Met Ala Ala Asp
115 120 125
Ile Leu Gly Gln Val Ala Asp Thr Ala Ala Gln Tyr Gly Ile Thr Leu
130 135 140
Gly Leu Glu Val Val Asn Arg Tyr Glu Thr Asn Val Leu Asn Thr Ala
145 150 155 160
Ser Gln Gly Val Glu Leu Ile Glu Arg Ile Gly Arg Pro Asn Val Lys
165 170 175
Val His Leu Asp Thr Tyr His Met Asn Ile Glu Glu Ser Asp Ile Met
180 185 190
Ser Ala Ile Arg Asp Thr Gly Asp Arg Leu Gly Tyr Phe His Ile Gly
195 200 205
Asp Ser His Arg Gly Tyr Leu Gly Ser Gly Asn Val Asp Phe Thr Ala
210 215 220
Val Phe Arg Ala Leu Val Phe Ser Gly Tyr Thr Gly Pro Ile Thr Phe
225 230 235 240
Glu Ser Phe Ser Ser Arg Val Val Gly Gln Pro Leu Glu Gly Ile Leu
245 250 255
Ala Ile Trp Arg Asn Leu Trp Glu Asp Ser Arg Asp Leu Ala Ser His
260 265 270
Ala Leu Ala Tyr Thr Arg Val Gln Leu Lys Ser Ala Gln Glu Ala Leu
275 280 285
Lys Gln Ala Glu Arg Ser Arg Leu Pro
290 295
<210> 19
<211> 897
<212> DNA
<213> 人工序列
<220>
<223> 变体230339的编码序列
<400> 19
atgaataagt taggtgtgca cgcattagtt tgggaagcgg gttggagtcg tgatgagtgt 60
gctcgtgcca tcgcacgcac cgcggaaacg ggatttgact tcattgaagt cccagcgtta 120
gatccggcaa gcattgatgc agagtttact cgcagagagt tagaacgcca tgggttggga 180
gtaacctttt cgcttggact cgatgcgcaa acagacatta gttctggtga tccggaacgc 240
gcagcgcggg gtaaagctaa attaaaagat gtcttacgtg tagcccggga ttgtggagcg 300
actcatgtct gtggaattct ctatagtgca tttcaaaaaa atgcagttcc tacgacccgt 360
gcgggtgtcg ccatggccgc ggacatttta ggacaggtag ctgatactgc agcacaatac 420
ggtattactt tggggttaga agtcgttaac cgttatgaga caaatgtatt gaacaccgcg 480
tcacagggtg ttgaactttg cgagcgtatt ggtcgtccca acgtaaaagt gcatttagat 540
acgtatcaca tgaatattga agagagcgat attatgagcg cgatcagaga tacgggagac 600
aggctagggt atttccatat tggcgattct catcgtggtt acctgggttc cggaaacgtc 660
gactttactg ccgtatttag ggcgctggta ttttctggat atacgggacc gattgttttt 720
gagtcattct ccagtagagt cgtaggacaa ccattagagg gaattctggc aatttggcgt 780
aatttatggg aagattcccg cgatctagct agtcacgcct tagcatatac tcgtgtccag 840
ttaaaatctg ctcaagaagc cctaaaacaa gccgagcgca gtcgcttacc gtgataa 897
<210> 20
<211> 297
<212> PRT
<213> 人工序列
<220>
<223> 变体230339
<400> 20
Met Asn Lys Leu Gly Val His Ala Leu Val Trp Glu Ala Gly Trp Ser
1 5 10 15
Arg Asp Glu Cys Ala Arg Ala Ile Ala Arg Thr Ala Glu Thr Gly Phe
20 25 30
Asp Phe Ile Glu Val Pro Ala Leu Asp Pro Ala Ser Ile Asp Ala Glu
35 40 45
Phe Thr Arg Arg Glu Leu Glu Arg His Gly Leu Gly Val Thr Phe Ser
50 55 60
Leu Gly Leu Asp Ala Gln Thr Asp Ile Ser Ser Gly Asp Pro Glu Arg
65 70 75 80
Ala Ala Arg Gly Lys Ala Lys Leu Asp Asp Val Leu Arg Val Ala Arg
85 90 95
Asp Cys Gly Ala Thr His Val Ser Gly Ile Leu Tyr Ser Ala Phe Gln
100 105 110
Lys Asn Ala Val Pro Thr Thr Arg Ala Glu Val Ala Met Ala Ala Asp
115 120 125
Ile Leu Gly Gln Val Ala Asp Thr Ala Ala Gln Tyr Gly Ile Thr Leu
130 135 140
Gly Leu Glu Val Val Asn Arg Tyr Glu Thr Asn Val Leu Asn Thr Ala
145 150 155 160
Ser Gln Gly Val Glu Leu Cys Glu Arg Ile Gly Arg Pro Asn Val Lys
165 170 175
Val His Leu Asp Thr Tyr His Met Asn Ile Glu Glu Ser Asp Ile Met
180 185 190
Ser Ala Ile Arg Asp Thr Gly Asp Arg Leu Gly Tyr Phe His Ile Gly
195 200 205
Asp Ser His Arg Gly Tyr Leu Gly Ser Gly Asn Val Asp Phe Thr Ala
210 215 220
Val Phe Arg Ala Leu Val Phe Ser Gly Tyr Thr Gly Pro Ile Thr Phe
225 230 235 240
Glu Ser Phe Ser Ser Arg Val Val Gly Gln Pro Leu Glu Gly Ile Leu
245 250 255
Ala Ile Trp Arg Asn Leu Trp Glu Asp Ser Arg Asp Leu Ala Ser His
260 265 270
Ala Leu Ala Tyr Thr Arg Val Gln Leu Lys Ser Ala Gln Glu Ala Leu
275 280 285
Lys Gln Ala Glu Arg Ser Arg Leu Pro
290 295
<210> 21
<211> 897
<212> DNA
<213> 人工序列
<220>
<223> 变体248843的编码序列
<400> 21
atgaataagt taggtgtgca cgcattagtt tgggaagcgg gttggagtcg tgatgagtgt 60
gctcgtgcca tcgcacgcac cgcggaaacg ggatttgact tcattgaagt cccagcgtta 120
gatccggcaa gcattgatgc agagtttact cgcagagagt tagaacgcca tgggttggga 180
gtaacctttt cgcttggact cgatgcgcaa acagacatta gttctggtga tccggaacgc 240
gcagcgcggg gtaaagctaa attaaaagat gtcttacgtg tagcccggga ttgtggagcg 300
actcatgtct gtggaattct ctatagtgca ctgcaaaaaa atgcagttcc tacgacccgt 360
gcgggtgtcg ccatggccgc ggacatttta ggacaggtag ctgatactgc agcacaatac 420
ggtattactt tggggttaga agtcgttaac cgttatgaga caaatgtatt gaacaccgcg 480
tcacagggtg ttgaacttat tgagcgtatt ggtcgtccca acgtaaaagt gcatttagat 540
acgtatcaca tgaatattga agagagcgat attatgagcg cgatcagaga tacgggagac 600
aggctagggt atttccatat tggcgattct catcgtggtt acctgggttc cggaaacgtc 660
gactttactg ccgtatttag ggcgctggta ttttctggat atacgggacc gattacattt 720
gagtcattct ccagtagagt cgtaggacaa ccattagagg gaattctggc aatttggcgt 780
aatttatggg aagattccgc agatctagct agtcacgcct tagcatttac tcgtgtccag 840
ttaaaatctg ctcaagaagc cctaaaacaa gccgagcgca gtcgcttacc gtgataa 897
<210> 22
<211> 297
<212> PRT
<213> 人工序列
<220>
<223> 变体248843
<400> 22
Met Asn Lys Leu Gly Val His Ala Leu Val Trp Glu Ala Gly Trp Ser
1 5 10 15
Arg Asp Glu Cys Ala Arg Ala Ile Ala Arg Thr Ala Glu Thr Gly Phe
20 25 30
Asp Phe Ile Glu Val Pro Ala Leu Asp Pro Ala Ser Ile Asp Ala Glu
35 40 45
Phe Thr Arg Arg Glu Leu Glu Arg His Gly Leu Gly Val Thr Phe Ser
50 55 60
Leu Gly Leu Asp Ala Gln Thr Asp Ile Ser Ser Gly Asp Pro Glu Arg
65 70 75 80
Ala Ala Arg Gly Lys Ala Lys Leu Asp Asp Val Leu Arg Val Ala Arg
85 90 95
Asp Cys Gly Ala Thr His Val Cys Gly Ile Leu Tyr Ser Ala Phe Gln
100 105 110
Lys Asn Ala Val Pro Thr Thr Arg Ala Gly Val Ala Met Ala Ala Asp
115 120 125
Ile Leu Gly Gln Val Ala Asp Thr Ala Ala Gln Tyr Gly Ile Thr Leu
130 135 140
Gly Leu Glu Val Val Asn Arg Tyr Glu Ser Asn Val Leu Asn Thr Ala
145 150 155 160
Ser Gln Gly Val Glu Leu Cys Glu Arg Ile Gly Arg Pro Asn Val Lys
165 170 175
Val His Leu Asp Thr Phe His Met Asn Ile Glu Glu Ser Asp Ile Met
180 185 190
Ser Ala Ile Arg Asp Thr Gly Asp Arg Leu Gly Tyr Phe His Ile Gly
195 200 205
Asp Ser His Arg Gly Tyr Leu Gly Ser Gly Asn Val Asp Phe Thr Ala
210 215 220
Ile Phe Arg Ala Leu Val Phe Ser Gly Tyr Thr Gly Pro Ile Thr Ile
225 230 235 240
Glu Ser Phe Ser Ser Arg Val Val Gly Gln Pro Leu Glu Gly Ile Leu
245 250 255
Ala Ile Trp Arg Asn Leu Trp Glu Asp Ser Arg Asp Leu Ala Ser His
260 265 270
Ala Leu Ala Tyr Thr Arg Val Gln Leu Lys Ser Ala Gln Glu Ala Leu
275 280 285
Lys Gln Ala Glu Arg Ser Arg Leu Pro
290 295
<210> 23
<211> 897
<212> DNA
<213> 人工序列
<220>
<223> 变体248867的编码序列
<400> 23
atgaataagt taggtgtgca cgcattagtt tgggaagcgg gttggagtcg tgatgagtgt 60
gctcgtgcca tcgcacgcac cgcggaaacg ggatttgact tcattgaagt cccagcgtta 120
gatccggcaa gcattgatgc agagtttact cgcagagagt tagaacgcca tgggttggga 180
gtaacctttt cgcttggact cgatgcgcaa acagacatta gttctggtga tccggaacgc 240
gcagcgcggg gtaaagctaa attaaaagat gtcttacgtg tagcccggga ttgtggagcg 300
actcatgtct gtggaattct ctatagtgca tttcaaaaat atgcagttcc tacgacccgt 360
gcgggtgtcg ccatggccgc ggacatttta agacaggtag ctgatactgc agcacaatac 420
ggtattactt tggggttaga agtcgttaac cgttatgaga caaatgtatt gaacaccgcg 480
tcacagggtg ttgaacttat tgagcgtatt ggtcgtccca acgtaaaagt gcatttagat 540
acgtatcaca tgaatattga agagagcgat attatgagcg cgatcagaga tacgggatca 600
aggctagggt atttccatat tggcgattct catcgtggtt acctgggttc cggaaacgtc 660
gactttactg ccgtatttag ggcgctggta ttttctggat atacgggacc gattacattt 720
gagtcattct ccagtagagt cgtaggacaa ccattagagg gaattctggc aatttggcgt 780
aatttatggg aagattcccg cgatctagct agtcacgcct tagcatatac tcgtgtccag 840
ttaaaatctg ctcaagaagc cctaaaacaa gccgagcgca gtcgcttacc gtgataa 897
<210> 24
<211> 297
<212> PRT
<213> 人工序列
<220>
<223> 变体248867
<400> 24
Met Asn Lys Leu Gly Val His Ala Leu Val Trp Glu Ala Gly Trp Ser
1 5 10 15
Arg Asp Glu Cys Ala Arg Ala Ile Ala Arg Thr Ala Glu Thr Gly Phe
20 25 30
Asp Phe Ile Glu Val Pro Ala Leu Asp Pro Ala Ser Ile Asp Ala Glu
35 40 45
Phe Thr Arg Arg Glu Leu Glu Arg His Gly Leu Gly Val Thr Phe Ser
50 55 60
Leu Gly Leu Asp Ala Gln Thr Asp Ile Ser Ser Gly Asp Pro Glu Arg
65 70 75 80
Ala Ala Arg Gly Lys Ala Lys Leu Asp Asp Val Leu Arg Val Ala Arg
85 90 95
Asp Cys Gly Ala Thr His Val Cys Gly Ile Leu Tyr Ser Ala Phe Gln
100 105 110
Lys Asn Ala Val Pro Thr Thr Arg Ala Gly Val Ala Met Ala Ala Asp
115 120 125
Ile Leu Gly Gln Val Ala Asp Thr Ala Glu Gln Tyr Gly Ile Thr Leu
130 135 140
Gly Leu Glu Val Val Asn Arg Tyr Glu Ser Asn Val Leu Asn Thr Ala
145 150 155 160
Ser Gln Gly Val Glu Leu Cys Glu Arg Ile Gly Arg Pro Asn Val Lys
165 170 175
Val His Leu Asp Thr Tyr His Met Asn Ile Glu Glu Ser Asp Ile Met
180 185 190
Ser Ala Ile Arg Asp Thr Gly Asp Arg Leu Gly Tyr Phe His Ile Gly
195 200 205
Asp Ser His Arg Gly Tyr Leu Gly Ser Gly Asn Val Asp Phe Thr Ala
210 215 220
Val Phe Arg Ala Leu Val Phe Ser Gly Tyr Thr Gly Pro Ile Thr Val
225 230 235 240
Glu Ser Phe Ser Ser Arg Val Val Gly Gln Pro Leu Glu Gly Ile Leu
245 250 255
Ala Ile Trp Arg Asn Leu Trp Glu Asp Ser Arg Asp Val Ala Ser His
260 265 270
Ala Leu Ala Tyr Thr Arg Val Gln Leu Lys Ser Ala Gln Glu Ala Leu
275 280 285
Lys Gln Ala Glu Arg Ser Arg Leu Pro
290 295
<210> 25
<211> 897
<212> DNA
<213> 人工序列
<220>
<223> 变体248891的编码序列
<400> 25
atgaataagt taggtgtgca cgcattagtt tgggaagcgg gttggagtcg tgatgagtgt 60
gctcgtgcca tcgcacgcac cgcggaaacg ggatttgact tcattgaagt cccagcgtta 120
gatccggcaa gcattgatgc agagtttact cgcagagagt tagaacgcta tgggttggga 180
gtaacctttt cgcttggact cgatgcgcaa acagacatta gttctggtga tccggaacgc 240
gcagcgcggg gtaaagctaa attaaaagat gtcttacgtg tagcccggga ttgtggagcg 300
actcatgtct gtggaattct ctatagtgca tttcaaaaaa atgcagttcc tacgacccgt 360
gcgggtgtcg ccatggccgc ggacatttta ggacaggtag ctgatactgc agcacaatac 420
ggtattactt tggggttaga agtcgttaac cgttatgaga caaatgtatt gaacaccgcg 480
tcacagggtg ttgaacttat tgagcgtatt ggtcgtccca acgtaaaagt gcatttagat 540
acgtatcaca tgaatattga agagagcgat attatgagcg cgatcagaga tacgggagac 600
aggctagggt atttccatat tggcgaatct catcgtggtt acctgggttc cggaaacgtc 660
gactttactg ccgtatttag ggcgctggta ttttctggat atcaaggacc gattacattt 720
gagtcattct ccagtagagt cgtaggacaa ccattagagg gaattctggc aatttggcgt 780
aatttatggg aagattcccg cgatctagct agtcacgcct tagcatatac tcgtgcacag 840
ttaaaatctg ctcaagaagc cctaaaacaa gccgagcgca gtcgcttacc gtgataa 897
<210> 26
<211> 297
<212> PRT
<213> 人工序列
<220>
<223> 变体248891
<400> 26
Met Asn Lys Leu Gly Val His Ala Leu Val Trp Glu Ala Gly Trp Ser
1 5 10 15
Arg Asp Glu Cys Ala Arg Ala Ile Ala Arg Thr Ala Glu Thr Gly Phe
20 25 30
Asp Phe Ile Glu Val Pro Ala Leu Asp Pro Ala Ser Ile Asp Ala Glu
35 40 45
Phe Thr Arg Arg Glu Leu Glu Arg His Gly Leu Gly Val Thr Phe Ser
50 55 60
Leu Gly Leu Asp Ala Gln Thr Asp Ile Ser Ser Gly Asp Pro Glu Arg
65 70 75 80
Ala Ala Arg Gly Lys Ala Lys Leu Asp Asp Val Leu Arg Val Ala Arg
85 90 95
Asp Cys Gly Ala Thr His Val Cys Gly Ile Leu Tyr Ser Ala Phe Gln
100 105 110
Lys Asn Ala Val Pro Thr Thr Arg Ala Gly Val Ala Met Ala Ala Asp
115 120 125
Ala Leu Gly Gln Val Ala Asp Thr Ala Ala Gln Tyr Gly Ile Thr Leu
130 135 140
Gly Leu Glu Val Val Asn Arg Tyr Glu Ser Asn Val Leu Asn Thr Ala
145 150 155 160
Ser Asp Gly Val Glu Leu Cys Glu Arg Ile Gly Arg Pro Asn Val Lys
165 170 175
Val His Leu Asp Thr Tyr His Met Asn Ile Glu Glu Ser Asp Ile Met
180 185 190
Ser Ala Ile Arg Asp Thr Gly Asp Arg Leu Gly Tyr Phe His Ile Gly
195 200 205
Asp Ser His Arg Gly Tyr Leu Gly Ser Gly Asn Val Asp Phe Thr Ala
210 215 220
Val Phe Arg Ala Leu Val Phe Ser Gly Tyr Thr Gly Pro Ile Thr Phe
225 230 235 240
Glu Cys Phe Ser Ser Arg Val Val Gly Gln Pro Leu Glu Gly Ile Leu
245 250 255
Ala Ile Trp Arg Asn Leu Trp Glu Asp Ser Arg Asp Leu Ala Ser His
260 265 270
Ala Leu Ala Tyr Thr Arg Val Gln Leu Lys Ser Ala Gln Glu Ala Leu
275 280 285
Lys Gln Ala Glu Arg Ser Arg Leu Pro
290 295
<210> 27
<211> 897
<212> DNA
<213> 人工序列
<220>
<223> 变体248907的编码序列
<400> 27
atgaataagt taggtgtgca cgcattagtt tgggaagcgg gttggagtcg tgatgagtgt 60
gctcgtgcca tcgcacgcac cgcggaaacg ggatttgact tcattgaagt cccagcgtta 120
gatccggcaa gcattgatgc agagtttact cgcagagagt tagaacgcta tgggttggga 180
gtaacctttt cgcttggact cgatgcgcaa acagacatta gttctggtga tccggaacgc 240
gcagcgcggg gtaaagctaa attaaaagat gtcttacgtg tagcccggga ttgtggagcg 300
actcatgtct gtggaattct ctatagtgca tttcaaaaaa atgcagttcc tacgacccgt 360
gcgggtgtcg ccatggccgc ggacatttta agacaggtag ctgatactgc agcacaatac 420
ggtattactt tggggttaga agtcgttaac cgttatgaga caaatgtatt gaacaccgcg 480
tcacagggtg ttgaacttat tgagcgtatt ggtcgtccca acgtaaaagt gcatttagat 540
acgtatcaca tgaatattga agagagcgat attatgagcg cgatcagaga tacgggagac 600
aggctagggt atttccatat tggcgattct catcgtggtt acctgggttc cggaaacgtc 660
gactttactg ccgtatttag ggcgctggta ttttctggat atacgggacc gattacattt 720
gagtcattct ccagtagagt cgtaggacaa ccattagagg gaattctggc aatttggcgt 780
aatttatggg aagatggccg cgatctagct agtcacgcct tagcatatac tcgtgtccag 840
ttaaaatctg ctcaagaagc cctaaaacaa gccgagcgca gtcgcttacc gtgataa 897
<210> 28
<211> 297
<212> PRT
<213> 人工序列
<220>
<223> 变体248907
<400> 28
Met Asn Lys Leu Gly Val His Ala Leu Leu Trp Glu Ala Gly Trp Ser
1 5 10 15
Arg Asp Glu Cys Ala Arg Ala Ile Ala Arg Thr Ala Glu Thr Gly Phe
20 25 30
Asp Phe Ile Glu Ile Pro Ala Leu Asp Pro Ala Ser Ile Asp Ala Glu
35 40 45
Phe Thr Arg Arg Glu Leu Glu Arg His Gly Leu Gly Val Thr Phe Ser
50 55 60
Leu Gly Leu Asp Ala Gln Thr Asp Ile Ser Ser Gly Asp Pro Glu Arg
65 70 75 80
Ala Ala Arg Gly Lys Ala Lys Leu Asp Asp Val Leu Arg Val Ala Arg
85 90 95
Asp Cys Gly Ala Thr His Val Cys Gly Ile Leu Tyr Ser Ala Phe Gln
100 105 110
Lys Asn Ala Val Pro Thr Thr Arg Ala Gly Val Ala Met Ala Ala Asp
115 120 125
Ile Leu Gly Gln Val Ala Asp Thr Ala Ala Gln Tyr Gly Ile Thr Leu
130 135 140
Gly Leu Glu Val Val Asn Arg Tyr Glu Ser Asn Val Leu Asn Thr Ala
145 150 155 160
Ser Gln Gly Val Glu Leu Cys Glu Arg Ile Gly Arg Pro Asn Val Lys
165 170 175
Val His Leu Asp Thr Tyr His Met Asn Ile Glu Glu Ser Asp Ile Met
180 185 190
Ser Ala Ile Arg Asp Thr Gly Asp Arg Leu Gly Tyr Phe His Ile Gly
195 200 205
Asp Ser His Arg Gly Tyr Leu Gly Ser Gly Asn Val Asp Phe Thr Ala
210 215 220
Val Phe Arg Ala Leu Arg Phe Ser Gly Tyr Thr Gly Pro Ile Thr Phe
225 230 235 240
Glu Ser Phe Ser Ser Arg Val Val Gly Gln Pro Leu Glu Gly Ile Leu
245 250 255
Ala Ile Trp Arg Asn Leu Trp Glu Asp Ser Arg Asp Leu Ala Ser His
260 265 270
Ala Leu Ala Tyr Thr Arg Val Gln Leu Lys Ser Ala Gln Glu Ala Leu
275 280 285
Lys Gln Ala Glu Arg Ser Arg Leu Pro
290 295
<210> 29
<211> 897
<212> DNA
<213> 人工序列
<220>
<223> 变体248914的编码序列
<400> 29
atgaataagt taggtgtgca cgcattagtt tgggaagcgg gttggagtcg tgatgagtgt 60
gctcgtgcca tcgcacgcac cgcggaaacg ggatttgact tcattgaagt cccagcgtta 120
gatccggcaa gcattgatgc agagtttact cgcagagagt tagaacgcca tgggttggga 180
gtaacctttt cgcttggact cgatgcgcaa acagacatta gttctggtga tccggaacgc 240
gcagcgcggg gtaaagctaa attaaaagat gtcttacgtg tagcccggga ttgtggagcg 300
actcatgtct gtggaattct ctatagtgca tttcaaaaat atgcagttcc tacgacccgt 360
agaggtgtcg ccatggccgc ggacatttta ggacaggtag ctgatactgc agcacaatac 420
ggtattatgt tggggttaga agtcgttaac cgttatgaga caaatgtatt gaacaccgcg 480
tcacagggtg ttgaacttat tgagcgtatt ggtcgtccca acgtaaaagt gcatttagat 540
acgtatcaca tgaatattga agagagcgat attatgagcg cgatcagaga tacgggagac 600
aggctagggt atttccatat tggcgattct catcgtggtt acctgggttc cggaaacgtc 660
gactttactg ccgtatttag ggcgctggta ttttctggat atacgggacc gattacattt 720
gagtcattct ccagtagagt cgtaggacaa ccattagagg gaattctggc aatttggcgt 780
aatttatggg aagattcccg cgatctagct agtcacgcct tagcatatac tcgtgtccag 840
ttaaaatctg ctcaagaagc cctaaaacaa gccgagcgca gtcgcttacc gtgataa 897
<210> 30
<211> 297
<212> PRT
<213> 人工序列
<220>
<223> 变体248914
<400> 30
Met Asn Lys Leu Gly Val His Ala Leu Val Trp Glu Ala Gly Trp Ser
1 5 10 15
Arg Asp Glu Cys Ala Arg Ala Ile Ala Arg Thr Ala Glu Thr Gly Tyr
20 25 30
Asp Phe Ile Glu Leu Pro Ala Leu Asp Pro Ala Ser Ile Asp Ala Glu
35 40 45
Phe Thr Arg Arg Glu Leu Glu Arg His Gly Leu Gly Val Thr Phe Ser
50 55 60
Leu Gly Leu Asp Ala Gln Thr Asp Ile Ser Ser Gly Asp Pro Glu Arg
65 70 75 80
Ala Ala Arg Gly Lys Ala Lys Leu Asp Asp Val Leu Arg Val Ala Arg
85 90 95
Asp Cys Gly Ala Thr His Val Cys Gly Ile Leu Tyr Ser Ala Phe Gln
100 105 110
Lys Asn Ala Val Pro Thr Thr Arg Ala Gly Val Ala Met Ala Ala Asp
115 120 125
Ile Leu Gly Gln Val Ala Asp Thr Ala Glu Gln Tyr Gly Ile Thr Leu
130 135 140
Gly Leu Glu Val Val Asn Arg Tyr Glu Ser Asn Val Leu Asn Thr Ala
145 150 155 160
Ser Gln Gly Val Glu Leu Cys Glu Arg Ile Gly Arg Pro Asn Val Lys
165 170 175
Val His Leu Asp Thr Tyr His Met Asn Ile Glu Glu Ser Asp Ile Met
180 185 190
Ser Ala Ile Arg Asp Thr Gly Asp Arg Leu Gly Tyr Phe His Ile Gly
195 200 205
Asp Ser His Arg Gly Tyr Leu Gly Ser Gly Asn Val Asp Phe Thr Ala
210 215 220
Val Phe Arg Ala Leu Val Phe Ser Gly Tyr Thr Gly Pro Ile Thr Phe
225 230 235 240
Glu Ser Phe Ser Ser Arg Val Val Gly Gln Pro Leu Glu Gly Ile Leu
245 250 255
Ala Ile Trp Arg Asn Leu Trp Glu Asp Ser Arg Asp Leu Ala Ser His
260 265 270
Ala Leu Ala Tyr Thr Arg Val Gln Leu Lys Ser Ala Gln Glu Ala Leu
275 280 285
Lys Gln Ala Glu Arg Ser Arg Leu Pro
290 295
<210> 31
<211> 897
<212> DNA
<213> 人工序列
<220>
<223> 变体248925的编码序列
<400> 31
atgaataagt taggtgtgca cgcattagtt tgggaagcgg gttggagtcg tgatgagtgt 60
gctcgtgcca tcgcacgcac cgcggaaacg ggatttgact tcattgaagt cccagcgtta 120
gatccggcaa gcattgatgc agattttact cgcagagagt tagaacgcca tgggttggga 180
gtaacctttt cgcttggact cgatgcgcaa acagacatta gttctggtga tccggaacgc 240
gcagcgcggg gtaaagctaa attaaaagat gtcttacgtg tagcccggga ttgtggagcg 300
actcatgtct gtggaattct ctatagtgca tttcaaaaaa atgcagttcc tacgaccgca 360
gcgggtgtcg ccatggccgc ggacatttta ggacaggtag ctgatactgc agcacaatac 420
ggtattactt tggggttaga agtcgttaac cgttatgaga caaatgtatt gaacaccgcg 480
tcacagggtg ttgaacttat tgagcgtatt ggtcgtccca acgtaaaagt gcatttagat 540
acgtatcaca tgaatattga agagagcgat attatgagcg cgatcagaga tacgggatca 600
aggctagggt atttccatat tggcgattct catcgtggtt acctgggttc cggaaacgtc 660
gactttactg ccgtatttag ggcgctggta ttttctggat atacgggacc gattacattt 720
gagtcattct ccagtagagt cgtaggacaa ccattagagg gaattctggc aatttggcgt 780
aatttatggg aagattcccg cgatctagct agtcacgcct tagcatatac tcgtgtccag 840
ttaaaatctg ctcaagaagc cctaaaacaa gccgagcgca gtcgcttacc gtgataa 897
<210> 32
<211> 297
<212> PRT
<213> 人工序列
<220>
<223> 变体248925
<400> 32
Met Asn Lys Leu Gly Val His Ala Leu Val Trp Glu Ala Gly Trp Ser
1 5 10 15
Arg Asp Glu Cys Ala Arg Ala Ile Ala Arg Thr Ala Glu Thr Gly Phe
20 25 30
Asp Phe Ile Glu Val Pro Ala Leu Asp Pro Ala Ser Ile Asp Ala Glu
35 40 45
Phe Thr Arg Arg Glu Leu Glu Arg His Gly Leu Gly Val Thr Phe Ser
50 55 60
Leu Gly Leu Asp Ala Gln Thr Asp Ile Ser Ser Gly Asp Pro Glu Arg
65 70 75 80
Ala Ala Arg Gly Lys Ala Lys Leu Asp Asp Val Leu Arg Val Ala Arg
85 90 95
Asp Cys Gly Ala Thr His Val Cys Gly Ile Leu Tyr Ser Ala Phe Gln
100 105 110
Lys Asn Ala Val Pro Thr Thr Arg Ala Gly Val Ala Met Ala Ala Asp
115 120 125
Ile Leu Gly Gln Val Ala Asp Thr Ala Glu Gln Tyr Gly Ile Thr Leu
130 135 140
Gly Leu Glu Val Val Asn Arg Tyr Glu Ser Asn Val Leu Asn Thr Ala
145 150 155 160
Ser Gln Gly Val Glu Leu Cys Glu Arg Ile Gly Arg Pro Asn Val Lys
165 170 175
Val His Leu Asp Thr Tyr His Met Asn Ile Glu Glu Ser Asp Ile Met
180 185 190
Ser Ala Ile Arg Asp Thr Gly Asp Arg Leu Gly Tyr Phe His Ile Gly
195 200 205
Asp Ser His Arg Gly Tyr Leu Gly Ser Gly Asn Val Asp Phe Thr Ala
210 215 220
Val Phe Arg Ala Leu Val Phe Ser Gly Tyr Thr Gly Pro Ile Thr Met
225 230 235 240
Glu Ala Phe Ser Ser Arg Val Val Gly Gln Pro Leu Glu Gly Ile Leu
245 250 255
Ala Ile Trp Arg Asn Leu Trp Glu Asp Ser Arg Asp Leu Ala Ser His
260 265 270
Ala Leu Ala Tyr Thr Arg Val Gln Leu Lys Ser Ala Gln Glu Ala Leu
275 280 285
Lys Gln Ala Glu Arg Ser Arg Leu Pro
290 295
<210> 33
<211> 897
<212> DNA
<213> 人工序列
<220>
<223> 变体256382的编码序列
<400> 33
atgaataagt taggtgtgca cgcattagtt tgggaagcgg gttggagtcg tgatgagtgt 60
gctcgtgcca tcgcacgcac cgcggaaacg ggatttgact tcattgaagt cccagcgtta 120
gatccggcaa gcattgatgc agagtttact cgcagagagt tagaaaaata tgggttggga 180
gtaacctttt cgcttggact cgatgcgcaa acagacatta gttctggtga tccggaacgc 240
gcagcgcggg gtaaagctaa attaaaagat gtcttacgtg tagcccggga ttgtggagcg 300
actcatgtct gtggaattct ctatagtgca ctgcaaaaaa atgcagttcc tacgacccgt 360
agaggtgtcg ccatggccgc ggacatttta agacaggtag ctgatactgc agcacaatac 420
ggtattactt tggggttaga agtcgttaac cgttatgaga caaatgtatt gaacaccgcg 480
tcacagggtg ttgaacttat tgagcgtatt ggtcgtccca acgtaaaagt gcatttagat 540
acgtatcaca tgaatattga agagagcgat attatgagcg cgatcagaga tacgggagac 600
aggctagggt atttccatat tggcgattct catcgtggtt acctgggttc cggaaacgtc 660
gactttactg ccgtatttag ggcgctggta ttttctggat atacgggacc gattacattt 720
gagtcattct ccagtagagt cgtaggacaa ccattagagg gaattctggc aatttggcgt 780
aatttatggg aagatggccg cgatctagct agtcacgcct tagcatatac tcgtgtccag 840
ttaaaatctg ctcaagaagc cctaaaacaa gccgagcgca gtcgcttacc gtgataa 897
<210> 34
<211> 297
<212> PRT
<213> 人工序列
<220>
<223> 变体256382
<400> 34
Met Asn Lys Leu Gly Val His Ala Leu Val Trp Glu Ala Gly Trp Ser
1 5 10 15
Arg Asp Glu Cys Ala Arg Ala Ile Ala Arg Thr Ala Glu Thr Gly Tyr
20 25 30
Asp Phe Ile Glu Val Pro Ala Leu Asp Pro Ala Ser Ile Asp Ala Glu
35 40 45
Phe Thr Arg Arg Glu Leu Glu Arg His Gly Leu Gly Val Thr Phe Ser
50 55 60
Leu Gly Leu Asp Ala Gln Thr Asp Ile Ser Ser Gly Asp Pro Glu Arg
65 70 75 80
Ala Ala Arg Gly Lys Ala Lys Leu Asp Asp Val Leu Arg Val Ala Arg
85 90 95
Asp Cys Gly Ala Thr His Val Cys Gly Ile Leu Tyr Ser Ala Phe Gln
100 105 110
Lys Asn Ala Val Pro Thr Thr Arg Ala Gly Val Ala Met Ala Ala Asp
115 120 125
Ile Leu Gly Gln Val Ala Asp His Ala Ala Gln Tyr Gly Ile Thr Leu
130 135 140
Gly Leu Glu Val Val Asn Arg Tyr Glu Ser Asn Val Leu Asn Thr Ala
145 150 155 160
Ser Gln Gly Val Glu Leu Cys Glu Arg Ile Gly Arg Pro Asn Val Lys
165 170 175
Val His Leu Asp Thr Tyr His Met Asn Ile Glu Glu Ser Asp Ile Met
180 185 190
Ser Ala Ile Arg Asp Thr Gly Asp Arg Leu Gly Tyr Phe His Ile Gly
195 200 205
Asp Ser His Arg Gly Tyr Leu Gly Ser Gly Asn Val Asp Phe Thr Ala
210 215 220
Val Phe Arg Ala Leu Val Phe Ser Gly Tyr Thr Gly Pro Ile Thr Phe
225 230 235 240
Glu Ser Phe Ser Ser Arg Val Val Gly Gln Pro Leu Glu Gly Ile Leu
245 250 255
Ala Ile Trp Arg Asn Leu Trp Glu Asp Ser Arg Asp Leu Ala Ser His
260 265 270
Ala Leu Ala Tyr Leu Arg Val Gln Leu Lys Ser Ala Gln Glu Ala Leu
275 280 285
Lys Gln Ala Glu Arg Ser Arg Leu Pro
290 295
<210> 35
<211> 897
<212> DNA
<213> 人工序列
<220>
<223> 变体256406的编码序列
<400> 35
atgaataagt taggtgtgca cgcattagtt tgggaagcgg gttggagtcg tgatgagtgt 60
gctcgtgcca tcgcacgcac cgcggaaacg ggatttgact tcattgaagt cccagcgtta 120
gatccggcaa gcattgatgc agagtttact cgcagagagt tagaaaaaca tgggttggga 180
gtaacctttt cgcttggact cgatgcgcaa acagacgtta gttctggtga tccggaacgc 240
gcagcgcggg gtaaagctaa attaaaagat gtcttacgtg tagcccggga ttgtggagcg 300
actcatgtct gtggaattct ctatagtgca tttcaaaaat atgcagttcc tacgacccgt 360
agaggtgtcg ccatggccgc ggacatttta ggacaggtag ctgatactgc agcacaatac 420
ggtattactt tggggttaga agtcgttaac cgttatgaga caaatgtatt gaacaccgcg 480
tcacagggtg ttgaacttat tgagcgtatt ggtcgtccca acgtaaaagt gcatttagat 540
acgtatcaca tgaatattga agagagcgat attatgagcg cgatcagaga tacgggagac 600
aggctagggt atttccatat tggcgattct catcgtggtt acctgggttc cggaaacgtc 660
gactttactg ccgtatttag ggcgctggta ttttctggat atacgggacc gattacattt 720
gagtcattct ccagtagagt cgtaggacaa ccattagagg gaattctggc aatttggcgt 780
aatttatggg aagatggccg cgatctagct agtcacgcct tagcatatac tcgtgtccag 840
ttaaaatctg ctcaagaagc cctaaaacaa gccgagcgca gtcgcttacc gtgataa 897
<210> 36
<211> 297
<212> PRT
<213> 人工序列
<220>
<223> 变体256406
<400> 36
Met Asn Lys Leu Gly Val His Ala Leu Val Trp Glu Ala Gly Trp Ser
1 5 10 15
Arg Asp Glu Cys Ala Arg Ala Ile Ala Arg Thr Ala Glu Thr Gly Phe
20 25 30
Asp Phe Ile Glu Val Pro Ala Leu Asp Pro Ala Ser Ile Asp Ala Glu
35 40 45
Phe Thr Arg Arg Glu Leu Glu Arg His Gly Leu Gly Val Thr Phe Ser
50 55 60
Leu Gly Leu Asp Ala Gln Thr Asp Ile Ser Ser Gly Asp Pro Glu Arg
65 70 75 80
Ala Ala Arg Gly Lys Ala Lys Leu Asp Asp Val Leu Arg Val Ala Arg
85 90 95
Asp Cys Gly Ala Thr His Val Cys Gly Pro Leu Tyr Ser Ala Phe Gln
100 105 110
Lys Asn Ala Val Pro Thr Thr Arg Ala Gly Val Ala Met Ala Ala Asp
115 120 125
Ile Leu Gly Gln Val Ala Asp Thr Ala Ala Gln Tyr Gly Ile Thr Leu
130 135 140
Gly Leu Glu Val Val Asn Arg Tyr Glu Ser Asn Val Leu Asn Thr Ala
145 150 155 160
Ser Gln Gly Val Glu Leu Cys Glu Arg Ile Gly Arg Pro Asn Val Lys
165 170 175
Val His Leu Asp Thr Tyr His Met Asn Ile Glu Glu Ser Asp Ile Met
180 185 190
Ser Ala Ile Arg Asp Thr Gly Asp Arg Leu Gly Tyr Val His Ile Gly
195 200 205
Asp Ser Asn Arg Gly Tyr Leu Gly Ser Gly Asn Val Asp Phe Thr Ala
210 215 220
Val Phe Arg Ala Leu Val Phe Ser Gly Tyr Thr Gly Pro Ile Thr Phe
225 230 235 240
Glu Ser Phe Ser Ser Arg Val Val Gly Gln Pro Leu Glu Gly Ile Leu
245 250 255
Ala Ile Trp Arg Asn Leu Trp Glu Asp Ser Arg Asp Leu Ala Ser His
260 265 270
Ala Leu Ala Tyr Thr Arg Val Gln Leu Lys Ser Ala Gln Glu Ala Leu
275 280 285
Lys Gln Ala Glu Arg Ser Arg Leu Pro
290 295
<210> 37
<211> 897
<212> DNA
<213> 人工序列
<220>
<223> 变体255290的编码序列
<400> 37
atgaataagt taggtgtgca cgcattagtt tgggaagcgg gttggagtcg tgatgagtgt 60
gctcgtgcca tcgcacgcac cgcggaaacg ggatttgact tcattgaagt cccagcgtta 120
gatccggcaa gcattgatgc agagtttact cgcagagagt tagaacgcca tgggttggga 180
gtaacctttt cgcttggact cgatgcgcaa acagacatta gttctggtga tccggaacgc 240
gcagcgcggg gtaaagctaa attaaaagat gtcttacgtg tagcccggga ttgtggagcg 300
actcatgtct gtggaattct ctatagtgca tttcaaaaat atgcagttcc tacgacccgt 360
agaggtgtcg ccatggccgc ggacatttta ggacaggtag ctgatactgc agcacaatac 420
ggtattactt tggggttaga agtcgttaac cgttatgaga caaatgtatt gaacaccgcg 480
tcacagggtg ttgaacttat tgagcgtatt ggtcgtccca acgtaaaagt gcatttagat 540
acgtatcaca tgaatattga agagagcgat attatgagcg cgatcagaga tacgggagac 600
aggctagggt atttccatat tggcgattct catcgtggtt acctgggttc cggaaacgtc 660
gactttactg ccgtatttag ggcgctggta ttttctggat atacgggacc gattacattt 720
gagtcattct ccagtagagt cgtaggacaa ccattagagg gaattctggc aatttggcgt 780
aatttatggg aagattcccg cgatctagct agtcacgcct tagcatatac tcgtgtccag 840
ttaaaatctg ctcaagaagc cctaaaacaa gccgagcgca gtcgcttacc gtgataa 897
<210> 38
<211> 297
<212> PRT
<213> 人工序列
<220>
<223> 变体255290
<400> 38
Met Asn Lys Leu Gly Val His Ala Leu Val Trp Glu Ala Gly Trp Ser
1 5 10 15
Arg Asp Glu Cys Ala Arg Ala Ile Ala Arg Thr Ala Glu Thr Gly Phe
20 25 30
Asp Phe Ile Glu Val Pro Ala Leu Asp Pro Ala Ser Ile Asp Ala Glu
35 40 45
Phe Thr Arg Arg Glu Leu Glu Arg His Gly Leu Gly Val Thr Phe Ser
50 55 60
Leu Gly Leu Asp Ala Gln Thr Asp Ile Ser Ser Gly Asp Pro Glu Arg
65 70 75 80
Ala Ala Arg Gly Lys Ala Lys Leu Asp Asp Val Leu Arg Val Ala Arg
85 90 95
Asp Cys Gly Ala Thr His Val Cys Gly Ile Leu Tyr Ser Ala Phe Gln
100 105 110
Lys Asn Ala Val Pro Thr Thr Arg Ala Gly Val Ala Met Ala Ala Asp
115 120 125
Ile Leu Gly Gln Val Ala Asp Thr Ala Ala Gln Tyr Gly Ile Thr Leu
130 135 140
Gly Leu Glu Val Val Asn Arg Tyr Glu Thr Tyr Val Leu Asn Thr Ala
145 150 155 160
Ser Gln Gly Val Glu Leu Cys Glu Arg Ile Gly Arg Pro Asn Val Lys
165 170 175
Val His Leu Asp Thr Tyr His Met Asn Ile Glu Glu Ser Asp Ile Met
180 185 190
Ser Ala Ile Arg Asp Thr Gly Asp Arg Leu Gly Tyr Phe His Ile Gly
195 200 205
Asp Ser His Arg Gly Tyr Leu Gly Ser Gly Asn Val Asp Phe Thr Ala
210 215 220
Val Phe Arg Ala Leu Val Phe Ser Gly Tyr Thr Gly Pro Ile Thr Leu
225 230 235 240
Glu Ser Phe Ser Ser Arg Val Val Gly Gln Pro Leu Glu Gly Ile Leu
245 250 255
Ala Ile Trp Arg Asn Leu Trp Glu Asp Ser Arg Asp Leu Ala Ser His
260 265 270
Ala Leu Ala Tyr Thr Arg Val Gln Leu Lys Ser Ala Gln Glu Ala Leu
275 280 285
Lys Gln Ala Glu Arg Ser Arg Leu Pro
290 295
<210> 39
<211> 897
<212> DNA
<213> 人工序列
<220>
<223> 变体257999的编码序列
<400> 39
atgaataagt taggtgtgca cgcattagtt tgggaagcgg gttggagtcg tgatgagtgt 60
gctcgtgcca tcgcacgcac cgcggaaacg ggatttgact tcattgaagt cccagcgtta 120
gatccggcaa gcattgatgc agagtttact cgcagagagt tagaaaaaca tgggttggga 180
gtaacctttt cgcttggact cgatgcgcaa acagacatta gttctggtga tccggaacgc 240
gcagcgcggg gtaaagctaa attaaaagat gtcttacgtg tagcccggga ttgtggagcg 300
actcatgtct gtggaattct ctatagtgca tttcaaaaat atgcagttcc tacgacccgt 360
agaggtgtcg ccatggccgc ggacatttta ggacaggtag ctgatactgc agcacaatac 420
ggtattactt tggggttaga agtcgttaac cgttatgaga caaatgtatt gaacaccgcg 480
tcacagggtg ttgaacttat tgagcgtatt ggtcgtccca acgtaaaagt gcatttagat 540
acgtatcaca tgaatattga agagagcgat attatgagcg cgatcagaga tacgggagac 600
aggctagggt atttccatat tggcgattct catcgtggtt acctgggttc cggaaacgtc 660
gactttactg ccgtatttag ggcgctggta ttttctggat atacgggacc gattacattt 720
gagtcattct ccagtagagt cgtaggacaa ccattagagg gaattctggc aatttggcgt 780
aatttatggg aagatggccg cgatctagct agtcacgcct tagcatatac tcgtgtccag 840
ttaaaatctg ctcaagaagc cctaaaacaa gccgagcgca gtcgcttacc gtgataa 897
<210> 40
<211> 297
<212> PRT
<213> 人工序列
<220>
<223> 变体257999
<400> 40
Met Asn Lys Leu Gly Val His Ala Leu Val Trp Glu Ala Gly Trp Ser
1 5 10 15
Arg Asp Glu Cys Ala Arg Ala Ile Ala Arg Thr Ala Glu Thr Gly Phe
20 25 30
Asp Phe Ile Glu Val Pro Ala Leu Asp Pro Ala Ser Ile Asp Ala Glu
35 40 45
Phe Thr Arg Arg Glu Leu Glu Arg His Gly Leu Gly Val Thr Phe Ser
50 55 60
Leu Gly Leu Asp Ala Gln Thr Asp Ile Ser Ser Gly Asp Pro Glu Arg
65 70 75 80
Ala Ala Arg Gly Lys Ala Lys Leu Asp Asp Val Leu Arg Val Ala Arg
85 90 95
Asp Cys Gly Ala Thr His Val Gly Gly Ile Leu Tyr Ser Ala Phe Gln
100 105 110
Lys Asn Ala Val Pro Thr Thr Arg Ala Gly Val Ala Met Ala Ala Asp
115 120 125
Ile Leu Gly Gln Val Ala Asp Thr Ala Ala Gln Tyr Gly Ile Thr Leu
130 135 140
Gly Leu Glu Val Val Asn Arg Tyr Glu Ser Asn Val Leu Asn Thr Ala
145 150 155 160
Ser Gln Gly Val Glu Leu Cys Glu Arg Ile Gly Arg Pro Asn Val Lys
165 170 175
Val His Leu Asp Thr Tyr His Met Asn Ile Glu Glu Ser Asp Ile Met
180 185 190
Ser Ala Ile Arg Asp Thr Gly Asp Arg Leu Gly Tyr Phe His Ile Gly
195 200 205
Asp Ser His Arg Gly Tyr Leu Gly Ser Gly Asn Leu Asp Phe Thr Ala
210 215 220
Val Phe Arg Ala Leu Val Phe Ser Gly Tyr Thr Gly Pro Ile Thr Ile
225 230 235 240
Glu Ser Phe Ser Ser Arg Val Val Gly Gln Pro Leu Glu Gly Ile Leu
245 250 255
Ala Ile Trp Arg Asn Leu Trp Glu Asp Ser Arg Asp Leu Ala Ser His
260 265 270
Ala Leu Ala Tyr Thr Arg Val Gln Leu Lys Ser Ala Gln Glu Ala Leu
275 280 285
Lys Gln Ala Glu Arg Ser Arg Leu Pro
290 295
<210> 41
<211> 897
<212> DNA
<213> 人工序列
<220>
<223> 变体261731的编码序列
<400> 41
atgaataagt taggtgtgca cgcattagtt tgggaagcgg gttggagtcg tgatgagtgt 60
gctcgtgcca tcgcacgcac cgcggaaacg ggatttgact tcattgaagt cccagcgtta 120
gatccggcaa gcattgatgc agagtttact cgcagagagt tagaaaaaca tgggttggga 180
gtaacctttt cgcttggact cgatgcgcaa acagacatta gttctggtga tccggaacgc 240
gcagcgcggg gtaaagctaa attaaaagat gtcttacgtg tagcccggga ttgtggagcg 300
actcatgtct gtggaattct ctatagtgca tttcaaaaat atgcagttcc tacgaccgca 360
agaggtgtcg ccatggccgc ggacatttta ggacaggtag ctgatactgc agcacaatac 420
ggtattactt tggggttaga agtcgttaac cgttatgaga caaatgtatt gaacaccgcg 480
tcacagggtg ttgaacttat tgagcgtatt ggtcgtccca acgtaaaagt gcatttagat 540
acgtatcaca tgaatattga agagagcgat attatgagcg cgatcagaga tacggcagac 600
aggctagggt atttccatat tggcgaatct catcgtggtt acctgggttc cggaaacgtc 660
gactttactg ccgtatttag ggcgctggta ttttctggat atacgggacc gattacattt 720
gagtcattct ccagtagagt cgtaggacaa ccattagagg gaattctggc aatttggcgt 780
aatttatggg aagatggccg cgatctagct agtcacgcct tagcatttac tcgtgtccag 840
ttaaaatctg ctcaagaagc cctaaaacaa gccgagcgca gtcgcttacc gtgataa 897
<210> 42
<211> 297
<212> PRT
<213> 人工序列
<220>
<223> 变体261731
<400> 42
Met Asn Lys Leu Gly Val His Ala Leu Val Trp Glu Ala Gly Trp Ser
1 5 10 15
Arg Asp Glu Cys Ala Arg Ala Ile Ala Arg Thr Ala Glu Thr Gly Phe
20 25 30
Asp Phe Ile Glu Val Pro Ala Leu Asp Pro Ala Ser Ile Asp Ala Glu
35 40 45
Phe Thr Arg Arg Glu Leu Glu Arg His Gly Leu Gly Val Thr Phe Ser
50 55 60
Leu Gly Leu Asp Ala Gln Thr Asp Ile Ser Ser Gly Asp Pro Glu Arg
65 70 75 80
Ala Ala Arg Gly Lys Ala Lys Leu Asp Asp Val Leu Arg Val Ala Arg
85 90 95
Asp Cys Gly Ala Thr His Val Cys Gly Ile Leu Tyr Ser Ala Phe Gln
100 105 110
Lys Asn Ala Val Pro Thr Thr Arg Ala Gly Val Ala Met Ala Ala Asp
115 120 125
Ile Leu Gly Gln Val Ala Asp His Ala Ala Gln Tyr Gly Ile Thr Leu
130 135 140
Gly Leu Glu Pro Val Asn Arg Tyr Glu Ser Asn Val Leu Asn Thr Ala
145 150 155 160
Ser Gln Gly Val Glu Leu Cys Glu Arg Ile Gly Arg Pro Asn Val Lys
165 170 175
Val His Leu Asp Thr Tyr His Met Asn Ile Glu Glu Ser Asp Ile Met
180 185 190
Ser Ala Ile Arg Asp Thr Gly Asp Arg Leu Gly Tyr Phe His Ile Gly
195 200 205
Asp Ser His Arg Gly Tyr Leu Gly Ser Gly Asn Val Asp Phe Thr Ala
210 215 220
Val Phe Arg Ala Leu Val Phe Ser Gly Tyr Thr Gly Pro Ile Thr Phe
225 230 235 240
Glu Pro Phe Ser Ser Arg Val Val Gly Gln Pro Leu Glu Gly Ile Leu
245 250 255
Ala Ile Trp Arg Asn Leu Trp Glu Asp Ser Arg Asp Leu Ala Ser His
260 265 270
Ala Leu Ala Tyr Thr Arg Val Gln Leu Lys Ser Ala Gln Glu Ala Leu
275 280 285
Lys Gln Ala Glu Arg Ser Arg Leu Pro
290 295
<210> 43
<211> 897
<212> DNA
<213> 人工序列
<220>
<223> 变体261732的编码序列
<400> 43
atgaataagt taggtgtgca cgcattagtt tgggaagcgg gttggagtcg tgatgagtgt 60
gctcgtgcca tcgcacgcac cgcggaaacg ggatttgact tcattgaagt cccagcgtta 120
gatccggcaa gcattgatgc agagtttact cgcagagagt tagaaaaaca tgggttggga 180
gtaacctttt cgcttggact cgatgcgcaa tgcgacatta gttctggtga tccggaacgc 240
gcagcgcggg gtaaagctaa attaaaagat gtcttacgtg tagcccggga ttgtggagcg 300
actcatgtct gtggaattct ctatagtgca tttcaaaaat atgcagttcc tacgaccgca 360
agaggtgtcg ccatggccgc ggacatttta ggacaggtag ctgatactgc agcacaatac 420
ggtattactt tggggttaga agtcgttaac cgttatgaga caaatgtatt gaacaccgcg 480
tcacagggtg ttgaacttat tgagcgtatt ggtcgtccca acgtaaaagt gcatttagat 540
acgtatcaca tgaatattga agagagcgat attatgagcg cgatcagaga tacgggagac 600
aggctagggt atttccatat tggcgaatct catcgtggtt acctgggttc cggaaacgtc 660
gactttactg ccgtatttag ggcgctggta ttttctggat atacgggacc gattacattt 720
gagtcattct ccagtagagt cgtaggacaa ccattagagg gaattctggc aatttggcgt 780
aatttatggg aagatggccg cgatctagct agtcacgcct tagcatttac tcgtgtccag 840
ttaaaatctg ctcaagaagc cctaaaacaa gccgagcgca gtcgcttacc gtgataa 897
<210> 44
<211> 297
<212> PRT
<213> 人工序列
<220>
<223> 变体261732
<400> 44
Met Asn Lys Leu Gly Val His Ala Leu Leu Trp Glu Ala Gly Trp Ser
1 5 10 15
Arg Asp Glu Cys Ala Arg Ala Ile Ala Arg Thr Ala Glu Thr Gly Phe
20 25 30
Asp Phe Ile Glu Val Pro Ala Leu Asp Pro Ala Ser Ile Asp Ala Glu
35 40 45
Phe Thr Arg Arg Glu Leu Glu Arg His Gly Leu Gly Val Thr Phe Ser
50 55 60
Leu Gly Leu Asp Ala Gln Thr Asp Ile Ser Ser Gly Asp Pro Glu Arg
65 70 75 80
Ala Ala Arg Gly Lys Ala Lys Leu Asp Asp Val Leu Arg Val Ala Arg
85 90 95
Asp Cys Gly Ala Thr His Val Cys Gly Ile Leu Tyr Ser Ala Phe Gln
100 105 110
Lys Asn Ala Val Pro Thr Thr Arg Ala Gly Val Ala Met Ala Ala Asp
115 120 125
Ile Leu Gly Gln Val Ala Asp Thr Ala Ala Gln Tyr Gly Ile Thr Leu
130 135 140
Gly Leu Glu Pro Val Asn Arg Tyr Glu Ser Asn Val Leu Asn Thr Ala
145 150 155 160
Ser Gln Gly Val Glu Leu Cys Glu Arg Ile Gly Arg Pro Asn Val Lys
165 170 175
Val His Leu Asp Thr Tyr His Met Asn Ile Glu Glu Ser Asp Ile Met
180 185 190
Ser Ala Ile Arg Asp Thr Gly Asp Arg Leu Gly Tyr Val His Ile Gly
195 200 205
Asp Ser His Arg Gly Tyr Leu Gly Ser Gly Asn Val Asp Phe Thr Ala
210 215 220
Val Phe Arg Ala Leu Val Phe Ser Gly Tyr Thr Gly Pro Ile Thr Phe
225 230 235 240
Glu Ser Phe Ser Ser Arg Val Val Gly Gln Pro Leu Glu Gly Ile Leu
245 250 255
Ala Ile Trp Arg Asn Leu Trp Glu Asp Ser Arg Asp Leu Ala Ser His
260 265 270
Ala Leu Ala Tyr Thr Arg Val Gln Leu Lys Ser Ala Gln Glu Ala Leu
275 280 285
Lys Gln Ala Glu Arg Ser Arg Leu Pro
290 295
<210> 45
<211> 897
<212> DNA
<213> 人工序列
<220>
<223> 变体261733的编码序列
<400> 45
atgaataagt taggtgtgca cgcattagtt tgggaagcgg gttggagtcg tgatgagtgt 60
gctcgtgcca tcgcacgcac cgcggaaacg ggatttgact tcattgaagt cccagcgtta 120
gatccggcaa gcattgatgc agagtttact cgcagagagt tagaaaaaca tgggttggga 180
gtaacctttt cgcttggact cgatgcgcaa tgcgacatta gttctggtga tccggaacgc 240
gcagcgcggg gtaaagctaa attaaaagat gtcttacgtg tagcccggga ttgtggagcg 300
actcatgtct gtggaattct ctatagtgca tttcaaaaat atgcagttcc tacgaccgca 360
agaggtgtcg ccatggccgc ggacatttta ggacaggtag ctgatactgc agcacaatac 420
ggtattactt tggggttaga agtcgttaac cgttatgaga caaatgtatt gaacaccgcg 480
tcacagggtg ttgaacttat tgagcgtatt ggtcgtccca acgtaaaagt gcatttagat 540
acgtatcaca tgaatattga agagagcgat attatgagcg cgatcagaga tacggcagac 600
aggctagggt atttccatat tggcgaatct catcgtggtt acctgggttc cggaaacgtc 660
gactttactg ccgtatttag ggcgctggta ttttctggat atacgggacc gattacattt 720
gagtcattct ccagtagagt cgtaggacaa ccattagagg gaattctggc aatttggcgt 780
aatttatggg aagatggccg cgatctagct agtcacgcct tagcatatac tcgtgtccag 840
ttaaaatctg ctcaagaagc cctaaaacaa gccgagcgca gtcgcttacc gtgataa 897
<210> 46
<211> 297
<212> PRT
<213> 人工序列
<220>
<223> 变体261733
<400> 46
Met Asn Lys Leu Gly Val His Ala Leu Val Trp Glu Ala Gly Trp Ser
1 5 10 15
Arg Asp Glu Cys Ala Arg Ala Ile Ala Arg Thr Ala Glu Thr Gly Phe
20 25 30
Asp Phe Ile Glu Val Pro Ala Leu Asp Pro Ala Ser Ile Asp Ala Glu
35 40 45
Phe Thr Arg Arg Glu Leu Glu Arg His Gly Leu Gly Val Thr Phe Ser
50 55 60
Leu Gly Leu Asp Ala Gln Thr Asp Ile Ser Ser Gly Asp Pro Glu Arg
65 70 75 80
Ala Ala Arg Gly Lys Ala Lys Leu Asp Asp Val Leu Arg Val Ala Arg
85 90 95
Asp Cys Gly Ala Thr His Val Cys Gly Ile Leu Tyr Ser Ala Phe Gln
100 105 110
Lys Asn Ala Val Pro Thr Thr Arg Ala Gly Val Ala Met Ala Ala Asp
115 120 125
Ala Leu Gly Gln Val Ala Asp Thr Ala Ala Gln Tyr Gly Ile Thr Leu
130 135 140
Gly Leu Glu Val Val Asn Arg Tyr Glu Ser Asn Val Leu Asn Thr Ala
145 150 155 160
Ser Gln Gly Val Glu Leu Cys Glu Arg Ile Gly Arg Pro Asn Val Lys
165 170 175
Val His Leu Asp Thr Tyr His Met Asn Ile Glu Glu Ser Asp Ile Met
180 185 190
Ser Ala Ile Arg Asp Thr Gly Asp Arg Leu Gly Tyr Phe His Ile Gly
195 200 205
Asp Ser His Arg Gly Tyr Leu Gly Ser Gly Asn Val Asp Phe Thr Ala
210 215 220
Ile Phe Arg Ala Leu Val Phe Ser Gly Tyr Thr Gly Pro Ile Thr Phe
225 230 235 240
Glu Pro Phe Ser Ser Arg Val Val Gly Gln Pro Leu Glu Gly Ile Leu
245 250 255
Ala Ile Trp Arg Asn Leu Trp Glu Asp Ser Arg Asp Leu Ala Ser His
260 265 270
Ala Leu Ala Tyr Thr Arg Val Gln Leu Lys Ser Ala Gln Glu Ala Leu
275 280 285
Lys Gln Ala Glu Arg Ser Arg Leu Pro
290 295
<210> 47
<211> 897
<212> DNA
<213> 人工序列
<220>
<223> 变体261734的编码序列
<400> 47
atgaataagt taggtgtgca cgcattagtt tgggaagcgg gttggagtcg tgatgagtgt 60
gctcgtgcca tcgcacgcac cgcggaaacg ggatttgact tcattgaagt cccagcgtta 120
gatccggcaa gcattgatgc agagtttact cgcagagagt tagaaaaaca tgggttggga 180
gtaacctttt cgcttggact cgatgcgcaa tgcgacatta gttctggtga tccggaacgc 240
gcagcgcggg gtaaagctaa attaaaagat gtcttacgtg tagcccggga ttgtggagcg 300
actcatgtct gtggaattct ctatagtgca tttcaaaaat atgcagttcc tacgaccgca 360
agaggtgtcg ccatggccgc ggacatttta ggacaggtag ctgatactgc agcacaatac 420
ggtattactt tggggttaga agtcgttaac cgttatgaga caaatgtatt gaacaccgcg 480
tcacagggtg ttgaacttat tgagcgtatt ggtcgtccca acgtaaaagt gcatttagat 540
acgtatcaca tgaatattga agagagcgat attatgagcg cgatcagaga tacggcagac 600
aggctagggt atttccatat tggcgattct catcgtggtt acctgggttc cggaaacgtc 660
gactttactg ccgtatttag ggcgctggta ttttctggat atacgggacc gattacattt 720
gagtcattct ccagtagagt cgtaggacaa ccattagagg gaattctggc aatttggcgt 780
aatttatggg aagatggccg cgatctagct agtcacgcct tagcatttac tcgtgtccag 840
ttaaaatctg ctcaagaagc cctaaaacaa gccgagcgca gtcgcttacc gtgataa 897
<210> 48
<211> 297
<212> PRT
<213> 人工序列
<220>
<223> 变体261734
<400> 48
Met Asn Lys Leu Gly Val His Ala Leu Val Trp Glu Ala Gly Trp Ser
1 5 10 15
Arg Asp Glu Cys Ala Arg Ala Ile Ala Arg Thr Ala Glu Thr Gly Phe
20 25 30
Asp Phe Ile Glu Val Pro Ala Leu Asp Pro Ala Ser Ile Asp Ala Glu
35 40 45
Phe Thr Arg Arg Glu Leu Glu Arg His Gly Leu Gly Val Thr Phe Ser
50 55 60
Leu Gly Leu Asp Ala Gln Thr Asp Ile Ser Ser Gly Asp Pro Glu Arg
65 70 75 80
Ala Ala Arg Gly Lys Ala Lys Leu Asp Asp Val Leu Arg Val Ala Arg
85 90 95
Asp Cys Gly Ala Thr His Val Cys Gly Ile Leu Tyr Ser Ala Phe Gln
100 105 110
Lys Asn Ala Val Pro Thr Thr Arg Ala Gly Val Ala Met Ala Ala Asp
115 120 125
Ile Leu Gly Gln Val Ala Asp Thr Ala Ala Gln Tyr Gly Ile Thr Leu
130 135 140
Gly Leu Glu Val Val Asn Arg Tyr Glu Ser Asn Val Leu Asn Thr Ala
145 150 155 160
Ser Gln Gly Val Glu Leu Cys Glu Arg Ile Gly Arg Pro Asn Val Lys
165 170 175
Val His Leu Asp Thr Tyr His Met Asn Ile Glu Glu Ser Asp Ile Met
180 185 190
Ser Ala Ile Arg Asp Thr Gly Asp Arg Leu Gly Tyr Phe His Ile Gly
195 200 205
Asp Ser His Arg Gly Tyr Leu Gly Ser Gly Asn Val Asp Phe Thr Ala
210 215 220
Val Phe Arg Ala Leu Val Phe Ser Gly Tyr Thr Gly Pro Ile Thr Phe
225 230 235 240
Glu Ser Phe Ser Ser Arg Val Val Gly Gln Pro Leu Glu Gly Ile Leu
245 250 255
Ala Ile Trp Arg Asn Leu Trp Glu Asp Ser Arg Asp Leu Ala Ser His
260 265 270
Ala Leu Ala Tyr Thr Arg Val Gln Leu Lys Ser Ala Gln Glu Ala Leu
275 280 285
Lys Gln Ala Glu Arg Ser Arg Leu Pro
290 295
<210> 49
<211> 897
<212> DNA
<213> 人工序列
<220>
<223> 变体261735的编码序列
<400> 49
atgaataagt taggtgtgca cgcattagtt tgggaagcgg gttggagtcg tgatgagtgt 60
gctcgtgcca tcgcacgcac cgcggaaacg ggatttgact tcattgaagt cccagcgtta 120
gatccggcaa gcattgatgc agagtttact cgcagagagt tagaaaaaca tgggttggga 180
gtaacctttt cgcttggact cgatgcgcaa tgcgacatta gttctggtga tccggaacgc 240
gcagcgcggg gtaaagctaa attaaaagat gtcttacgtg tagcccggga ttgtggagcg 300
actcatgtct gtggaattct ctatagtgca tttcaaaaat atgcagttcc tacgacccgt 360
agaggtgtcg ccatggccgc ggacatttta ggacaggtag ctgatactgc agcacaatac 420
ggtattactt tggggttaga agtcgttaac cgttatgaga caaatgtatt gaacaccgcg 480
tcacagggtg ttgaacttat tgagcgtatt ggtcgtccca acgtaaaagt gcatttagat 540
acgtatcaca tgaatattga agagagcgat attatgagcg cgatcagaga tacggcagac 600
aggctagggt atttccatat tggcgaatct catcgtggtt acctgggttc cggaaacgtc 660
gactttactg ccgtatttag ggcgctggta ttttctggat atacgggacc gattacattt 720
gagtcattct ccagtagagt cgtaggacaa ccattagagg gaattctggc aatttggcgt 780
aatttatggg aagatggccg cgatctagct agtcacgcct tagcatttac tcgtgtccag 840
ttaaaatctg ctcaagaagc cctaaaacaa gccgagcgca gtcgcttacc gtgataa 897
<210> 50
<211> 297
<212> PRT
<213> 人工序列
<220>
<223> 变体261735
<400> 50
Met Asn Lys Leu Gly Val His Ala Leu Val Trp Glu Ala Gly Trp Ser
1 5 10 15
Arg Asp Glu Cys Ala Arg Ala Ile Ala Arg Thr Ala Glu Thr Gly Phe
20 25 30
Asp Phe Ile Glu Val Pro Ala Leu Asp Pro Ala Ser Ile Asp Ala Glu
35 40 45
Phe Thr Arg Arg Glu Leu Glu Arg His Gly Leu Gly Val Thr Phe Ser
50 55 60
Leu Gly Leu Asp Ala Gln Thr Asp Ile Ser Ser Gly Asp Pro Glu Arg
65 70 75 80
Ala Ala Arg Gly Lys Ala Lys Leu Asp Asp Val Leu Arg Val Ala Arg
85 90 95
Asp Cys Gly Ala Thr His Val Ser Gly Ile Leu Tyr Ser Ala Phe Gln
100 105 110
Lys Asn Ala Val Pro Thr Thr Arg Ala Gly Val Ala Met Ala Ala Asp
115 120 125
Ile Leu Gly Gln Val Ala Asp Thr Ala Glu Gln Tyr Gly Ile Thr Leu
130 135 140
Gly Leu Glu Val Val Asn Arg Tyr Glu Ser Asn Val Leu Asn Thr Ala
145 150 155 160
Ser Gln Gly Val Glu Leu Cys Glu Arg Ile Gly Arg Pro Asn Val Lys
165 170 175
Val His Leu Asp Thr Tyr His Met Asn Ile Glu Glu Ser Asp Ile Met
180 185 190
Ser Ala Ile Arg Asp Thr Gly Asp Arg Leu Gly Tyr Phe His Ile Gly
195 200 205
Asp Ser His Arg Gly Tyr Leu Gly Ser Gly Asn Val Asp Phe Thr Ala
210 215 220
Val Phe Arg Ala Leu Val Phe Ser Gly Tyr Thr Gly Pro Ile Thr Leu
225 230 235 240
Glu Ser Phe Ser Ser Arg Val Val Gly Gln Pro Leu Glu Gly Ile Leu
245 250 255
Ala Ile Trp Arg Asn Leu Trp Glu Asp Ser Arg Asp Leu Ala Ser His
260 265 270
Ala Leu Ala Tyr Thr Arg Val Gln Leu Lys Ser Ala Gln Glu Ala Leu
275 280 285
Lys Gln Ala Glu Arg Ser Arg Leu Pro
290 295
<210> 51
<211> 897
<212> DNA
<213> 人工序列
<220>
<223> 变体261736的编码序列
<400> 51
atgaataagt taggtgtgca cgcattagtt tgggaagcgg gttggagtcg tgatgagtgt 60
gctcgtgcca tcgcacgcac cgcggaaacg ggatttgact tcattgaagt cccagcgtta 120
gatccggcaa gcattgatgc agagtttact cgcagagagt tagaaaaaca tgggttggga 180
gtaacctttt cgcttggact cgatgcgcaa acagacatta gttctggtga tccggaacgc 240
gcagcgcggg gtaaagctaa attaaaagat gtcttacgtg tagcccggga ttgtggagcg 300
actcatgtct gtggaattct ctatagtgca tttcaaaaat atgcagttcc tacgaccgca 360
agaggtgtcg ccatggccgc ggacatttta ggacaggtag ctgatactgc agcacaatac 420
ggtattactt tggggttaga agtcgttaac cgttatgaga caaatgtatt gaacaccgcg 480
tcacagggtg ttgaacttat tgagcgtatt ggtcgtccca acgtaaaagt gcatttagat 540
acgtatcaca tgaatattga agagagcgat attatgagcg cgatcagaga tacgggagac 600
aggctagggt atttccatat tggcgaatct catcgtggtt acctgggttc cggaaacgtc 660
gactttactg ccgtatttag ggcgctggta ttttctggat atacgggacc gattacattt 720
gagtcattct ccagtagagt cgtaggacaa ccattagagg gaattctggc aatttggcgt 780
aatttatggg aagatggccg cgatctagct agtcacgcct tagcatttac tcgtgtccag 840
ttaaaatctg ctcaagaagc cctaaaacaa gccgagcgca gtcgcttacc gtgataa 897
<210> 52
<211> 297
<212> PRT
<213> 人工序列
<220>
<223> 变体261736
<400> 52
Met Asn Lys Leu Gly Val His Ala Leu Val Trp Glu Ala Gly Trp Ser
1 5 10 15
Arg Asp Glu Cys Ala Arg Ala Ile Ala Arg Thr Ala Glu Thr Gly Phe
20 25 30
Asp Phe Ile Glu Val Pro Ala Leu Asp Pro Ala Ser Ile Asp Ala Glu
35 40 45
Phe Thr Arg Arg Glu Leu Glu Arg His Gly Leu Gly Val Thr Phe Ser
50 55 60
Leu Gly Leu Asp Ala Gln Thr Asp Ile Ser Ser Gly Asp Pro Glu Arg
65 70 75 80
Ala Ala Arg Gly Lys Ala Lys Leu Asp Asp Val Leu Arg Val Ala Arg
85 90 95
Asp Cys Gly Ala Thr His Val Cys Gly Pro Leu Tyr Ser Ala Phe Gln
100 105 110
Lys Asn Ala Val Pro Thr Thr Arg Ala Gly Val Ala Met Ala Ala Asp
115 120 125
Ile Leu Gly Gln Val Ala Asp Thr Ala Ala Gln Tyr Gly Ile Thr Leu
130 135 140
Gly Leu Glu Val Val Asn Arg Tyr Glu Ser Asn Val Leu Asn Thr Ala
145 150 155 160
Ser Gln Gly Val Glu Leu Cys Glu Arg Ile Gly Arg Pro Asn Val Lys
165 170 175
Val Leu Leu Asp Thr Tyr His Met Asn Ile Glu Glu Ser Asp Ile Met
180 185 190
Ser Ala Ile Arg Asp Thr Gly Asp Arg Leu Gly Tyr Phe His Ile Gly
195 200 205
Asp Ser His Arg Gly Tyr Leu Gly Ser Gly Asn Ile Asp Phe Thr Ala
210 215 220
Val Phe Arg Ala Leu Val Phe Ser Gly Tyr Thr Gly Pro Ile Thr Phe
225 230 235 240
Glu Ser Phe Ser Ser Arg Val Val Gly Gln Pro Leu Glu Gly Ile Leu
245 250 255
Ala Ile Trp Arg Asn Leu Trp Glu Asp Ser Arg Asp Leu Ala Ser His
260 265 270
Ala Leu Ala Tyr Thr Arg Val Gln Leu Lys Ser Ala Gln Glu Ala Leu
275 280 285
Lys Gln Ala Glu Arg Ser Arg Leu Pro
290 295
<210> 53
<211> 897
<212> DNA
<213> 人工序列
<220>
<223> 变体261737的编码序列
<400> 53
atgaataagt taggtgtgca cgcattagtt tgggaagcgg gttggagtcg tgatgagtgt 60
gctcgtgcca tcgcacgcac cgcggaaacg ggatttgact tcattgaagt cccagcgtta 120
gatccggcaa gcattgatgc agagtttact cgcagagagt tagaaaaaca tgggttggga 180
gtaacctttt cgcttggact cgatgcgcaa acagacatta gttctggtga tccggaacgc 240
gcagcgcggg gtaaagctaa attaaaagat gtcttacgtg tagcccggga ttgtggagcg 300
actcatgtct gtggaattct ctatagtgca tttcaaaaat atgcagttcc tacgaccgca 360
agaggtgtcg ccatggccgc ggacatttta ggacaggtag ctgatactgc agcacaatac 420
ggtattactt tggggttaga agtcgttaac cgttatgaga caaatgtatt gaacaccgcg 480
tcacagggtg ttgaacttat tgagcgtatt ggtcgtccca acgtaaaagt gcatttagat 540
acgtatcaca tgaatattga agagagcgat attatgagcg cgatcagaga tacggcagac 600
aggctagggt atttccatat tggcgaatct catcgtggtt acctgggttc cggaaacgtc 660
gactttactg ccgtatttag ggcgctggta ttttctggat atacgggacc gattacattt 720
gagtcattct ccagtagagt cgtaggacaa ccattagagg gaattctggc aatttggcgt 780
aatttatggg aagatggccg cgatctagct agtcacgcct tagcatatac tcgtgtccag 840
ttaaaatctg ctcaagaagc cctaaaacaa gccgagcgca gtcgcttacc gtgataa 897
<210> 54
<211> 297
<212> PRT
<213> 人工序列
<220>
<223> 变体261737
<400> 54
Met Asn Lys Leu Gly Val His Ala Leu Val Trp Glu Ala Gly Trp Ser
1 5 10 15
Arg Asp Glu Cys Ala Arg Ala Ile Ala Arg Thr Ala Glu Thr Gly Phe
20 25 30
Asp Phe Ile Glu Val Pro Ala Leu Asp Pro Ala Ser Ile Asp Ala Glu
35 40 45
Phe Thr Arg Arg Glu Leu Glu Arg His Gly Leu Gly Val Thr Phe Ser
50 55 60
Leu Gly Leu Asp Ala Gln Thr Asp Ile Ser Ser Gly Asp Pro Glu Arg
65 70 75 80
Ala Ala Arg Gly Lys Ala Lys Leu Asp Asp Val Leu Arg Val Ala Arg
85 90 95
Asp Cys Gly Ala Thr His Val Ser Gly Ile Leu Tyr Ser Ala Phe Gln
100 105 110
Lys Asn Ala Val Pro Thr Thr Arg Ala Gly Val Ala Met Ala Ala Asp
115 120 125
Ile Leu Gly Gln Val Ala Asp Thr Ala Ala Gln Tyr Gly Ile Thr Leu
130 135 140
Gly Leu Glu Val Val Asn Arg Phe Glu Ser Asn Leu Leu Asn Thr Ala
145 150 155 160
Ser Gln Gly Val Glu Leu Cys Glu Arg Ile Gly Arg Pro Asn Val Lys
165 170 175
Val His Leu Asp Thr Tyr His Met Asn Ile Glu Glu Ser Asp Ile Met
180 185 190
Ser Ala Ile Arg Asp Thr Gly Asp Arg Leu Gly Tyr Phe His Ile Gly
195 200 205
Asp Ser His Arg Gly Tyr Leu Gly Ser Gly Asn Val Asp Phe Thr Ala
210 215 220
Val Phe Arg Ala Leu Val Phe Ser Gly Tyr Thr Gly Pro Ile Thr Phe
225 230 235 240
Glu Ser Phe Ser Ser Arg Val Val Gly Gln Pro Leu Glu Gly Ile Leu
245 250 255
Ala Ile Trp Arg Asn Leu Trp Glu Asp Ser Arg Asp Leu Ala Ser His
260 265 270
Ala Leu Ala Tyr Thr Arg Val Gln Leu Lys Ser Ala Gln Glu Ala Leu
275 280 285
Lys Gln Ala Glu Arg Ser Arg Leu Pro
290 295
<210> 55
<211> 897
<212> DNA
<213> 人工序列
<220>
<223> 变体261738的编码序列
<400> 55
atgaataagt taggtgtgca cgcattagtt tgggaagcgg gttggagtcg tgatgagtgt 60
gctcgtgcca tcgcacgcac cgcggaaacg ggatttgact tcattgaagt cccagcgtta 120
gatccggcaa gcattgatgc agagtttact cgcagagagt tagaaaaaca tgggttggga 180
gtaacctttt cgcttggact cgatgcgcaa tgcgacatta gttctggtga tccggaacgc 240
gcagcgcggg gtaaagctaa attaaaagat gtcttacgtg tagcccggga ttgtggagcg 300
actcatgtct gtggaattct ctatagtgca tttcaaaaat atgcagttcc tacgaccgca 360
agaggtgtcg ccatggccgc ggacatttta ggacaggtag ctgatactgc agcacaatac 420
ggtattactt tggggttaga agtcgttaac cgttatgaga caaatgtatt gaacaccgcg 480
tcacagggtg ttgaacttat tgagcgtatt ggtcgtccca acgtaaaagt gcatttagat 540
acgtatcaca tgaatattga agagagcgat attatgagcg cgatcagaga tacgggagac 600
aggctagggt atttccatat tggcgaatct catcgtggtt acctgggttc cggaaacgtc 660
gactttactg ccgtatttag ggcgctggta ttttctggat atacgggacc gattacattt 720
gagtcattct ccagtagagt cgtaggacaa ccattagagg gaattctggc aatttggcgt 780
aatttatggg aagatggccg cgatctagct agtcacgcct tagcatatac tcgtgtccag 840
ttaaaatctg ctcaagaagc cctaaaacaa gccgagcgca gtcgcttacc gtgataa 897
<210> 56
<211> 297
<212> PRT
<213> 人工序列
<220>
<223> 变体261738
<400> 56
Met Asn Lys Ile Gly Val His Ala Leu Val Trp Glu Ala Gly Trp Ser
1 5 10 15
Arg Asp Glu Cys Ala Arg Ala Ile Ala Arg Thr Ala Glu Thr Gly Phe
20 25 30
Asp Phe Ile Glu Val Pro Ala Leu Asp Pro Ala Ser Ile Asp Ala Glu
35 40 45
Phe Thr Arg Arg Glu Leu Glu Arg His Gly Leu Gly Val Thr Phe Ser
50 55 60
Leu Gly Leu Asp Ala Gln Thr Asp Ile Ser Ser Gly Asp Pro Glu Arg
65 70 75 80
Ala Ala Arg Gly Lys Ala Lys Leu Asp Asp Val Leu Arg Val Ala Arg
85 90 95
Asp Cys Gly Ala Thr His Val Cys Gly Ile Leu Tyr Ser Ala Phe Gln
100 105 110
Lys Asn Ala Val Pro Thr Thr Arg Ala Glu Val Ala Met Ala Ala Asp
115 120 125
Ile Leu Gly Gln Val Ala Asp Thr Ala Ala Gln Tyr Gly Ile Thr Leu
130 135 140
Gly Leu Glu Pro Val Asn Arg Tyr Glu Ser Asn Val Leu Asn Thr Ala
145 150 155 160
Ser Gln Gly Val Glu Leu Cys Glu Arg Ile Gly Arg Pro Asn Val Lys
165 170 175
Val His Leu Asp Thr Tyr His Met Asn Ile Glu Glu Ser Asp Ile Met
180 185 190
Ser Ala Ile Arg Asp Thr Gly Asp Arg Leu Gly Tyr Phe His Ile Gly
195 200 205
Asp Ser His Arg Gly Tyr Leu Gly Ser Gly Asn Val Asp Phe Thr Ala
210 215 220
Val Phe Arg Ala Leu Val Phe Ser Gly Tyr Thr Gly Pro Ile Thr Phe
225 230 235 240
Glu Ser Phe Ser Ser Arg Val Val Gly Gln Pro Leu Glu Gly Ile Leu
245 250 255
Ala Ile Trp Arg Asn Leu Trp Glu Asp Ser Arg Asp Leu Ala Ser His
260 265 270
Ala Leu Ala Tyr Thr Arg Val Gln Leu Lys Ser Ala Gln Glu Ala Leu
275 280 285
Lys Gln Ala Glu Arg Ser Arg Leu Pro
290 295
<210> 57
<211> 897
<212> DNA
<213> 人工序列
<220>
<223> 变体261739的编码序列
<400> 57
atgaataagt taggtgtgca cgcattagtt tgggaagcgg gttggagtcg tgatgagtgt 60
gctcgtgcca tcgcacgcac cgcggaaacg ggatttgact tcattgaagt cccagcgtta 120
gatccggcaa gcattgatgc agagtttact cgcagagagt tagaaaaaca tgggttggga 180
gtaacctttt cgcttggact cgatgcgcaa acagacatta gttctggtga tccggaacgc 240
gcagcgcggg gtaaagctaa attaaaagat gtcttacgtg tagcccggga ttgtggagcg 300
actcatgtct gtggaattct ctatagtgca tttcaaaaat atgcagttcc tacgacccgt 360
agaggtgtcg ccatggccgc ggacatttta ggacaggtag ctgatactgc agcacaatac 420
ggtattactt tggggttaga agtcgttaac cgttatgaga caaatgtatt gaacaccgcg 480
tcacagggtg ttgaacttat tgagcgtatt ggtcgtccca acgtaaaagt gcatttagat 540
acgtatcaca tgaatattga agagagcgat attatgagcg cgatcagaga tacggcagac 600
aggctagggt atttccatat tggcgaatct catcgtggtt acctgggttc cggaaacgtc 660
gactttactg ccgtatttag ggcgctggta ttttctggat atacgggacc gattacattt 720
gagtcattct ccagtagagt cgtaggacaa ccattagagg gaattctggc aatttggcgt 780
aatttatggg aagatggccg cgatctagct agtcacgcct tagcatttac tcgtgtccag 840
ttaaaatctg ctcaagaagc cctaaaacaa gccgagcgca gtcgcttacc gtgataa 897
<210> 58
<211> 297
<212> PRT
<213> 人工序列
<220>
<223> 变体261739
<400> 58
Met Asn Lys Leu Gly Val His Ala Leu Val Trp Glu Ala Gly Trp Ser
1 5 10 15
Arg Asp Glu Cys Ala Arg Ala Ile Ala Arg Thr Ala Glu Thr Gly Phe
20 25 30
Asp Phe Ile Glu Val Pro Ala Leu Asp Pro Ala Ser Ile Asp Ala Glu
35 40 45
Phe Thr Arg Arg Glu Leu Glu Arg His Gly Leu Gly Val Thr Phe Ser
50 55 60
Leu Gly Leu Asp Ala Gln Thr Asp Ile Ser Ser Gly Asp Pro Glu Arg
65 70 75 80
Ala Ala Arg Gly Lys Ala Lys Leu Asp Asp Val Leu Arg Val Ala Arg
85 90 95
Asp Cys Gly Ala Thr His Val Gly Gly Ile Leu Tyr Ser Ala Phe Gln
100 105 110
Lys Asn Ala Val Pro Thr Thr Arg Ala Gly Val Ala Met Ala Ala Asp
115 120 125
Ile Leu Gly Gln Val Ala Asp Thr Ala Ala Gln Tyr Gly Ile Thr Leu
130 135 140
Gly Leu Glu Val Val Asn Arg Tyr Glu Ser Asn Val Leu Asn Thr Ala
145 150 155 160
Ser Asp Gly Val Glu Leu Cys Glu Arg Ile Gly Arg Pro Asn Val Lys
165 170 175
Val Leu Leu Asp Thr Tyr His Met Asn Ile Glu Glu Ser Asp Ile Met
180 185 190
Ser Ala Ile Arg Asp Thr Gly Asp Arg Leu Gly Tyr Phe His Ile Gly
195 200 205
Asp Ser His Arg Gly Tyr Leu Gly Ser Gly Asn Val Asp Phe Thr Ala
210 215 220
Val Phe Arg Ala Leu Val Phe Ser Gly Tyr Thr Gly Pro Ile Thr Phe
225 230 235 240
Glu Ser Phe Ser Ser Arg Val Val Gly Gln Pro Leu Glu Gly Ile Leu
245 250 255
Ala Ile Trp Arg Asn Leu Trp Glu Asp Ser Arg Asp Leu Ala Ser His
260 265 270
Ala Leu Ala Tyr Thr Arg Val Gln Leu Lys Ser Ala Gln Glu Ala Leu
275 280 285
Lys Gln Ala Glu Arg Ser Arg Leu Pro
290 295
<210> 59
<211> 897
<212> DNA
<213> 人工序列
<220>
<223> 变体261740的编码序列
<400> 59
atgaataagt taggtgtgca cgcattagtt tgggaagcgg gttggagtcg tgatgagtgt 60
gctcgtgcca tcgcacgcac cgcggaaacg ggatttgact tcattgaagt cccagcgtta 120
gatccggcaa gcattgatgc agagtttact cgcagagagt tagaaaaaca tgggttggga 180
gtaacctttt cgcttggact cgatgcgcaa tgcgacatta gttctggtga tccggaacgc 240
gcagcgcggg gtaaagctaa attaaaagat gtcttacgtg tagcccggga ttgtggagcg 300
actcatgtct gtggaattct ctatagtgca tttcaaaaat atgcagttcc tacgacccgt 360
agaggtgtcg ccatggccgc ggacatttta ggacaggtag ctgatactgc agcacaatac 420
ggtattactt tggggttaga agtcgttaac cgttatgaga caaatgtatt gaacaccgcg 480
tcacagggtg ttgaacttat tgagcgtatt ggtcgtccca acgtaaaagt gcatttagat 540
acgtatcaca tgaatattga agagagcgat attatgagcg cgatcagaga tacgggagac 600
aggctagggt atttccatat tggcgaatct catcgtggtt acctgggttc cggaaacgtc 660
gactttactg ccgtatttag ggcgctggta ttttctggat atacgggacc gattacattt 720
gagtcattct ccagtagagt cgtaggacaa ccattagagg gaattctggc aatttggcgt 780
aatttatggg aagatggccg cgatctagct agtcacgcct tagcatttac tcgtgtccag 840
ttaaaatctg ctcaagaagc cctaaaacaa gccgagcgca gtcgcttacc gtgataa 897
<210> 60
<211> 297
<212> PRT
<213> 人工序列
<220>
<223> 变体261740
<400> 60
Met Asn Lys Leu Gly Val His Ala Leu Val Trp Glu Ala Gly Trp Ser
1 5 10 15
Arg Asp Glu Cys Ala Arg Ala Ile Ala Arg Thr Ala Glu Thr Gly Phe
20 25 30
Asp Phe Ile Glu Ile Pro Ala Leu Asp Pro Ala Ser Ile Asp Ala Glu
35 40 45
Phe Thr Arg Arg Glu Leu Glu Arg His Gly Leu Gly Val Thr Phe Ser
50 55 60
Leu Gly Leu Asp Ala Gln Thr Asp Ile Ser Ser Gly Asp Pro Glu Arg
65 70 75 80
Ala Ala Arg Gly Lys Ala Lys Leu Asp Asp Val Leu Arg Val Ala Arg
85 90 95
Asp Cys Gly Ala Thr His Val Ser Gly Ile Leu Tyr Ser Ala Phe Gln
100 105 110
Lys Asn Ala Val Pro Thr Thr Arg Ala Gly Val Ala Met Ala Ala Asp
115 120 125
Ile Leu Gly Gln Val Ala Asp Thr Ala Ala Gln Tyr Gly Ile Thr Leu
130 135 140
Gly Leu Glu Val Val Asn Arg Tyr Glu Ser Asn Val Leu Asn Thr Ala
145 150 155 160
Ser Gln Gly Val Glu Leu Cys Glu Arg Ile Gly Arg Pro Asn Val Lys
165 170 175
Val His Leu Asp Thr Tyr His Met Asn Ile Glu Glu Ser Asp Ile Met
180 185 190
Ser Ala Ile Arg Asp Thr Gly Asp Arg Leu Gly Tyr Phe His Ile Gly
195 200 205
Asp Ser His Arg Gly Tyr Leu Gly Ser Gly Asn Val Asp Phe Thr Ala
210 215 220
Val Phe Arg Ala Leu Val Phe Ser Gly Tyr Thr Gly Pro Leu Thr Phe
225 230 235 240
Glu Ser Phe Ser Ser Arg Val Val Gly Gln Pro Leu Glu Gly Ile Leu
245 250 255
Ala Ile Trp Arg Asn Leu Trp Glu Asp Ser Arg Asp Leu Ala Ser His
260 265 270
Ala Leu Ala Tyr Thr Arg Val Gln Leu Lys Ser Ala Gln Glu Ala Leu
275 280 285
Lys Gln Ala Glu Arg Ser Arg Leu Pro
290 295
<210> 61
<211> 897
<212> DNA
<213> 人工序列
<220>
<223> 变体261741的编码序列
<400> 61
atgaataagt taggtgtgca cgcattagtt tgggaagcgg gttggagtcg tgatgagtgt 60
gctcgtgcca tcgcacgcac cgcggaaacg ggatttgact tcattgaagt cccagcgtta 120
gatccggcaa gcattgatgc agagtttact cgcagagagt tagaaaaaca tgggttggga 180
gtaacctttt cgcttggact cgatgcgcaa tgcgacatta gttctggtga tccggaacgc 240
gcagcgcggg gtaaagctaa attaaaagat gtcttacgtg tagcccggga ttgtggagcg 300
actcatgtct gtggaattct ctatagtgca tttcaaaaat atgcagttcc tacgacccgt 360
agaggtgtcg ccatggccgc ggacatttta ggacaggtag ctgatactgc agcacaatac 420
ggtattactt tggggttaga agtcgttaac cgttatgaga caaatgtatt gaacaccgcg 480
tcacagggtg ttgaacttat tgagcgtatt ggtcgtccca acgtaaaagt gcatttagat 540
acgtatcaca tgaatattga agagagcgat attatgagcg cgatcagaga tacggcagac 600
aggctagggt atttccatat tggcgattct catcgtggtt acctgggttc cggaaacgtc 660
gactttactg ccgtatttag ggcgctggta ttttctggat atacgggacc gattacattt 720
gagtcattct ccagtagagt cgtaggacaa ccattagagg gaattctggc aatttggcgt 780
aatttatggg aagatggccg cgatctagct agtcacgcct tagcatttac tcgtgtccag 840
ttaaaatctg ctcaagaagc cctaaaacaa gccgagcgca gtcgcttacc gtgataa 897
<210> 62
<211> 297
<212> PRT
<213> 人工序列
<220>
<223> 变体261741
<400> 62
Met Asn Lys Phe Gly Val His Ala Leu Val Trp Glu Ala Gly Trp Ser
1 5 10 15
Arg Asp Glu Cys Ala Arg Ala Ile Ala Arg Thr Ala Glu Thr Gly Phe
20 25 30
Asp Phe Ile Glu Val Pro Ala Leu Asp Pro Ala Ser Ile Asp Ala Glu
35 40 45
Phe Thr Arg Arg Glu Leu Glu Arg His Gly Leu Gly Val Thr Phe Ser
50 55 60
Leu Gly Leu Asp Ala Gln Thr Asp Ile Ser Ser Gly Asp Pro Glu Arg
65 70 75 80
Ala Ala Arg Gly Lys Ala Lys Leu Asp Asp Val Leu Arg Val Ala Arg
85 90 95
Asp Cys Gly Ala Thr His Val Cys Gly Ile Leu Tyr Ser Ala Phe Gln
100 105 110
Lys Asn Ala Val Pro Thr Thr Arg Ala Gly Val Ala Met Ala Ala Asp
115 120 125
Ile Leu Gly Gln Val Ala Asp Thr Ala Ala Gln Tyr Gly Ile Thr Leu
130 135 140
Gly Leu Glu Val Val Asn Arg Tyr Glu Ser Asn Val Leu Asn Thr Ala
145 150 155 160
Ser Gln Gly Val Glu Leu Cys Glu Arg Ile Gly Arg Pro Asn Val Lys
165 170 175
Val His Leu Asp Thr Phe His Met Asn Ile Glu Glu Ser Asp Ile Met
180 185 190
Ser Ala Ile Arg Asp Thr Gly Asp Arg Leu Gly Tyr Phe His Ile Gly
195 200 205
Asp Ser His Arg Gly Tyr Leu Gly Ser Gly Asn Val Asp Phe Thr Ala
210 215 220
Val Phe Arg Ala Leu Arg Phe Ser Gly Tyr Thr Gly Pro Ile Thr Phe
225 230 235 240
Glu Ser Phe Ser Ser Arg Val Val Gly Gln Pro Leu Glu Gly Ile Leu
245 250 255
Ala Ile Trp Arg Asn Leu Trp Glu Asp Ser Arg Asp Leu Ala Ser His
260 265 270
Ala Leu Ala Tyr Thr Arg Val Gln Leu Lys Ser Ala Gln Glu Ala Leu
275 280 285
Lys Gln Ala Glu Arg Ser Arg Leu Pro
290 295
<210> 63
<211> 897
<212> DNA
<213> 人工序列
<220>
<223> 变体261742的编码序列
<400> 63
atgaataagt taggtgtgca cgcattagtt tgggaagcgg gttggagtcg tgatgagtgt 60
gctcgtgcca tcgcacgcac cgcggaaacg ggatttgact tcattgaagt cccagcgtta 120
gatccggcaa gcattgatgc agagtttact cgcagagagt tagaaaaaca tgggttggga 180
gtaacctttt cgcttggact cgatgcgcaa acagacatta gttctggtga tccggaacgc 240
gcagcgcggg gtaaagctaa attaaaagat gtcttacgtg tagcccggga ttgtggagcg 300
actcatgtct gtggaattct ctatagtgca tttcaaaaat atgcagttcc tacgaccgca 360
agaggtgtcg ccatggccgc ggacatttta ggacaggtag ctgatactgc agcacaatac 420
ggtattactt tggggttaga agtcgttaac cgttatgaga caaatgtatt gaacaccgcg 480
tcacagggtg ttgaacttat tgagcgtatt ggtcgtccca acgtaaaagt gcatttagat 540
acgtatcaca tgaatattga agagagcgat attatgagcg cgatcagaga tacggcagac 600
aggctagggt atttccatat tggcgattct catcgtggtt acctgggttc cggaaacgtc 660
gactttactg ccgtatttag ggcgctggta ttttctggat atacgggacc gattacattt 720
gagtcattct ccagtagagt cgtaggacaa ccattagagg gaattctggc aatttggcgt 780
aatttatggg aagatggccg cgatctagct agtcacgcct tagcatttac tcgtgtccag 840
ttaaaatctg ctcaagaagc cctaaaacaa gccgagcgca gtcgcttacc gtgataa 897
<210> 64
<211> 297
<212> PRT
<213> 人工序列
<220>
<223> 变体261742
<400> 64
Met Asn Lys Leu Gly Val His Ala Leu Val Trp Glu Ala Gly Trp Ser
1 5 10 15
Arg Asp Glu Cys Ala Arg Ala Ile Ala Arg Thr Ala Glu Thr Gly Phe
20 25 30
Asp Phe Ile Glu Leu Pro Ala Leu Asp Pro Ala Ser Ile Asp Ala Glu
35 40 45
Phe Thr Arg Arg Glu Leu Glu Arg His Gly Leu Gly Val Thr Phe Ser
50 55 60
Leu Gly Leu Asp Ala Gln Thr Asp Ile Ser Ser Gly Asp Pro Glu Arg
65 70 75 80
Ala Ala Arg Gly Lys Ala Lys Leu Asp Asp Val Leu Arg Val Ala Arg
85 90 95
Asp Cys Gly Ala Thr His Val Gly Gly Ile Leu Tyr Ser Ala Phe Gln
100 105 110
Lys Asn Ala Val Pro Thr Thr Arg Ala Gly Val Ala Met Ala Ala Asp
115 120 125
Ile Leu Gly Gln Val Ala Asp Thr Ala Ala Gln Tyr Gly Ile Thr Leu
130 135 140
Ala Leu Glu Val Val Asn Arg Tyr Glu Ser Asn Val Leu Asn Thr Ala
145 150 155 160
Ser Gln Gly Val Glu Leu Cys Glu Arg Ile Gly Arg Pro Asn Val Lys
165 170 175
Val His Leu Asp Thr Tyr His Met Asn Ile Glu Glu Ser Asp Ile Met
180 185 190
Ser Ala Ile Arg Asp Thr Gly Asp Arg Leu Gly Tyr Phe His Ile Gly
195 200 205
Asp Ser His Arg Gly Tyr Leu Gly Ser Gly Asn Val Asp Phe Thr Ala
210 215 220
Val Phe Arg Ala Leu Val Phe Ser Gly Tyr Thr Gly Pro Ile Thr Phe
225 230 235 240
Glu Ser Phe Ser Ser Arg Val Val Gly Gln Pro Leu Glu Gly Ile Leu
245 250 255
Ala Ile Trp Arg Asn Leu Trp Glu Asp Ser Arg Asp Leu Ala Ser His
260 265 270
Ala Leu Ala Tyr Thr Arg Val Gln Leu Lys Ser Ala Gln Glu Ala Leu
275 280 285
Lys Gln Ala Glu Arg Ser Arg Leu Pro
290 295
<210> 65
<211> 897
<212> DNA
<213> 人工序列
<220>
<223> 变体261743的编码序列
<400> 65
atgaataagt taggtgtgca cgcattagtt tgggaagcgg gttggagtcg tgatgagtgt 60
gctcgtgcca tcgcacgcac cgcggaaacg ggatttgact tcattgaagt cccagcgtta 120
gatccggcaa gcattgatgc agagtttact cgcagagagt tagaaaaaca tgggttggga 180
gtaacctttt cgcttggact cgatgcgcaa tgcgacatta gttctggtga tccggaacgc 240
gcagcgcggg gtaaagctaa attaaaagat gtcttacgtg tagcccggga ttgtggagcg 300
actcatgtct gtggaattct ctatagtgca tttcaaaaat atgcagttcc tacgaccgca 360
agaggtgtcg ccatggccgc ggacatttta ggacaggtag ctgatactgc agcacaatac 420
ggtattactt tggggttaga agtcgttaac cgttatgaga caaatgtatt gaacaccgcg 480
tcacagggtg ttgaacttat tgagcgtatt ggtcgtccca acgtaaaagt gcatttagat 540
acgtatcaca tgaatattga agagagcgat attatgagcg cgatcagaga tacgggagac 600
aggctagggt atttccatat tggcgattct catcgtggtt acctgggttc cggaaacgtc 660
gactttactg ccgtatttag ggcgctggta ttttctggat atacgggacc gattacattt 720
gagtcattct ccagtagagt cgtaggacaa ccattagagg gaattctggc aatttggcgt 780
aatttatggg aagatggccg cgatctagct agtcacgcct tagcatttac tcgtgtccag 840
ttaaaatctg ctcaagaagc cctaaaacaa gccgagcgca gtcgcttacc gtgataa 897
<210> 66
<211> 297
<212> PRT
<213> 人工序列
<220>
<223> 变体261743
<400> 66
Met Asn Lys Leu Gly Val His Ala Leu Val Trp Glu Ala Gly Trp Ser
1 5 10 15
Arg Asp Glu Cys Ala Arg Ala Ile Ala Arg Thr Ala Glu Thr Gly Phe
20 25 30
Asp Phe Ile Glu Val Pro Ala Leu Asp Pro Ala Ser Ile Asp Ala Glu
35 40 45
Phe Thr Arg Arg Glu Leu Glu Arg His Gly Leu Gly Val Thr Phe Ser
50 55 60
Leu Gly Leu Asp Ala Gln Thr Asp Ile Ser Ser Pro Asp Pro Glu Arg
65 70 75 80
Ala Ala Arg Gly Lys Ala Lys Leu Asp Asp Val Leu Arg Val Ala Arg
85 90 95
Asp Cys Gly Ala Thr His Val Cys Gly Ile Leu Tyr Ser Ala Phe Gln
100 105 110
Lys Asn Ala Val Pro Thr Thr Arg Ala Gly Val Ala Met Ala Ala Asp
115 120 125
Ile Leu Gly Gln Val Ala Asp Thr Ala Ala Gln Tyr Gly Ile Thr Leu
130 135 140
Gly Leu Glu Val Val Asn Arg Tyr Glu Ser Asn Val Leu Asn Thr Ala
145 150 155 160
Ser Gln Gly Val Glu Leu Ile Glu Arg Ile Gly Arg Pro Asn Val Lys
165 170 175
Val His Leu Asp Thr Tyr His Met Asn Ile Glu Glu Ser Asp Ile Met
180 185 190
Ser Ala Ile Arg Asp Thr Gly Asp Arg Leu Gly Tyr Phe His Ile Gly
195 200 205
Asp Ser His Arg Gly Tyr Leu Gly Ser Gly Asn Val Asp Trp Thr Ala
210 215 220
Val Phe Arg Ala Leu Val Phe Ser Gly Tyr Thr Gly Pro Ile Thr Phe
225 230 235 240
Glu Ser Phe Ser Ser Arg Val Val Gly Gln Pro Leu Glu Gly Ile Leu
245 250 255
Ala Ile Trp Arg Asn Leu Trp Glu Asp Ser Arg Asp Leu Ala Ser His
260 265 270
Ala Leu Ala Tyr Thr Arg Val Gln Leu Lys Ser Ala Gln Glu Ala Leu
275 280 285
Lys Gln Ala Glu Arg Ser Arg Leu Pro
290 295
<210> 67
<211> 897
<212> DNA
<213> 人工序列
<220>
<223> 变体261744的编码序列
<400> 67
atgaataagt taggtgtgca cgcattagtt tgggaagcgg gttggagtcg tgatgagtgt 60
gctcgtgcca tcgcacgcac cgcggaaacg ggatttgact tcattgaagt cccagcgtta 120
gatccggcaa gcattgatgc agagtttact cgcagagagt tagaaaaaca tgggttggga 180
gtaacctttt cgcttggact cgatgcgcaa tgcgacatta gttctggtga tccggaacgc 240
gcagcgcggg gtaaagctaa attaaaagat gtcttacgtg tagcccggga ttgtggagcg 300
actcatgtct gtggaattct ctatagtgca tttcaaaaat atgcagttcc tacgacccgt 360
agaggtgtcg ccatggccgc ggacatttta ggacaggtag ctgatactgc agcacaatac 420
ggtattactt tggggttaga agtcgttaac cgttatgaga caaatgtatt gaacaccgcg 480
tcacagggtg ttgaacttat tgagcgtatt ggtcgtccca acgtaaaagt gcatttagat 540
acgtatcaca tgaatattga agagagcgat attatgagcg cgatcagaga tacggcagac 600
aggctagggt atttccatat tggcgaatct catcgtggtt acctgggttc cggaaacgtc 660
gactttactg ccgtatttag ggcgctggta ttttctggat atacgggacc gattacattt 720
gagtcattct ccagtagagt cgtaggacaa ccattagagg gaattctggc aatttggcgt 780
aatttatggg aagatggccg cgatctagct agtcacgcct tagcatatac tcgtgtccag 840
ttaaaatctg ctcaagaagc cctaaaacaa gccgagcgca gtcgcttacc gtgataa 897
<210> 68
<211> 297
<212> PRT
<213> 人工序列
<220>
<223> 变体261744
<400> 68
Met Asn Lys Leu Gly Val His Ala Leu Val Trp Glu Ala Gly Trp Ser
1 5 10 15
Arg Asp Glu Cys Ala Arg Ala Ile Ala Arg Thr Ala Glu Thr Gly Phe
20 25 30
Asp Phe Ile Glu Val Pro Ala Leu Asp Pro Ala Ser Ile Asp Ala Glu
35 40 45
Phe Thr Arg Arg Glu Leu Glu Arg His Gly Leu Gly Val Thr Phe Ser
50 55 60
Leu Gly Leu Asp Ala Gln Thr Asp Ile Ser Ser Gly Asp Pro Glu Arg
65 70 75 80
Ala Ala Arg Gly Lys Ala Lys Leu Asp Asp Val Leu Arg Val Ala Arg
85 90 95
Asp Cys Gly Ala Thr His Val Cys Gly Pro Leu Tyr Ser Ala Phe Gln
100 105 110
Lys Asn Ala Val Pro Thr Thr Arg Ala Gly Val Ala Met Ala Ala Asp
115 120 125
Ile Leu Gly Gln Val Ala Asp Thr Ala Ala Gln Tyr Gly Ile Thr Leu
130 135 140
Gly Leu Glu Val Leu Asn Arg Tyr Glu Ser Asn Val Leu Asn Thr Ala
145 150 155 160
Ser Glu Gly Val Glu Leu Cys Glu Arg Ile Gly Arg Pro Asn Val Lys
165 170 175
Val His Leu Asp Thr Tyr His Met Asn Ile Glu Glu Ser Asp Ile Met
180 185 190
Ser Ala Ile Arg Asp Thr Gly Asp Arg Leu Gly Tyr Phe His Ile Gly
195 200 205
Asp Ser His Arg Gly Tyr Leu Gly Ser Gly Asn Val Asp Phe Thr Ala
210 215 220
Val Phe Arg Ala Leu Val Phe Ser Gly Tyr Thr Gly Pro Ile Thr Phe
225 230 235 240
Glu Ser Phe Ser Ser Arg Val Val Gly Gln Pro Leu Glu Gly Ile Leu
245 250 255
Ala Ile Trp Arg Asn Leu Trp Glu Asp Ser Arg Asp Leu Ala Ser His
260 265 270
Ala Leu Ala Tyr Thr Arg Val Gln Leu Lys Ser Ala Gln Glu Ala Leu
275 280 285
Lys Gln Ala Glu Arg Ser Arg Leu Pro
290 295
<210> 69
<211> 897
<212> DNA
<213> 人工序列
<220>
<223> 变体261745的编码序列
<400> 69
atgaataagt taggtgtgca cgcattagtt tgggaagcgg gttggagtcg tgatgagtgt 60
gctcgtgcca tcgcacgcac cgcggaaacg ggatttgact tcattgaagt cccagcgtta 120
gatccggcaa gcattgatgc agagtttact cgcagagagt tagaaaaaca tgggttggga 180
gtaacctttt cgcttggact cgatgcgcaa tgcgacatta gttctggtga tccggaacgc 240
gcagcgcggg gtaaagctaa attaaaagat gtcttacgtg tagcccggga ttgtggagcg 300
actcatgtct gtggaattct ctatagtgca tttcaaaaat atgcagttcc tacgaccgca 360
agaggtgtcg ccatggccgc ggacatttta ggacaggtag ctgatactgc agcacaatac 420
ggtattactt tggggttaga agtcgttaac cgttatgaga caaatgtatt gaacaccgcg 480
tcacagggtg ttgaacttat tgagcgtatt ggtcgtccca acgtaaaagt gcatttagat 540
acgtatcaca tgaatattga agagagcgat attatgagcg cgatcagaga tacggcagac 600
aggctagggt atttccatat tggcgattct catcgtggtt acctgggttc cggaaacgtc 660
gactttactg ccgtatttag ggcgctggta ttttctggat atacgggacc gattacattt 720
gagtcattct ccagtagagt cgtaggacaa ccattagagg gaattctggc aatttggcgt 780
aatttatggg aagatggccg cgatctagct agtcacgcct tagcatatac tcgtgtccag 840
ttaaaatctg ctcaagaagc cctaaaacaa gccgagcgca gtcgcttacc gtgataa 897
<210> 70
<211> 297
<212> PRT
<213> 人工序列
<220>
<223> 变体261745
<400> 70
Met Asn Lys Leu Gly Val His Ala Leu Val Trp Glu Ala Gly Trp Ser
1 5 10 15
Arg Asp Glu Cys Ala Arg Ala Ile Ala Arg Thr Ala Glu Thr Gly Phe
20 25 30
Asp Phe Ile Glu Val Pro Ala Leu Asp Pro Ala Ser Ile Asp Ala Glu
35 40 45
Phe Thr Arg Arg Glu Leu Glu Arg His Gly Leu Gly Val Thr Phe Ser
50 55 60
Leu Gly Leu Asp Ala Gln Thr Asp Ile Ser Ser Gly Asp Pro Glu Arg
65 70 75 80
Ala Ala Arg Gly Lys Ala Lys Leu Asp Asp Val Leu Arg Val Ala Arg
85 90 95
Asp Cys Gly Ala Thr His Val Cys Gly Pro Leu Tyr Ser Ala Phe Gln
100 105 110
Lys Asn Ala Val Pro Thr Thr Arg Ala Gly Val Ala Met Ala Ala Asp
115 120 125
Ile Leu Gly Gln Val Ala Asp Thr Ala Ala Gln Tyr Gly Ile Thr Leu
130 135 140
Gly Leu Glu Val Val Asn Arg Tyr Glu Ser His Val Leu Asn Thr Ala
145 150 155 160
Ser Gln Gly Val Glu Leu Cys Glu Arg Ile Gly Arg Pro Asn Val Lys
165 170 175
Val His Leu Asp Thr Tyr His Met Asn Ile Glu Glu Ser Asp Ile Met
180 185 190
Ser Ala Ile Arg Asp Thr Gly Asp Arg Leu Gly Tyr Phe His Ile Gly
195 200 205
Asp Ser His Arg Gly Tyr Leu Gly Ser Gly Asn Val Asp Trp Thr Ala
210 215 220
Val Phe Arg Ala Leu Val Phe Ser Gly Tyr Thr Gly Pro Ile Thr Phe
225 230 235 240
Glu Ser Phe Ser Ser Arg Val Val Gly Gln Pro Leu Glu Gly Ile Leu
245 250 255
Ala Ile Trp Arg Asn Leu Trp Glu Asp Ser Arg Asp Leu Ala Ser His
260 265 270
Ala Leu Ala Tyr Thr Arg Val Gln Leu Lys Ser Ala Gln Glu Ala Leu
275 280 285
Lys Gln Ala Glu Arg Ser Arg Leu Pro
290 295
<210> 71
<211> 897
<212> DNA
<213> 人工序列
<220>
<223> 变体261746的编码序列
<400> 71
atgaataagt taggtgtgca cgcattagtt tgggaagcgg gttggagtcg tgatgagtgt 60
gctcgtgcca tcgcacgcac cgcggaaacg ggatttgact tcattgaagt cccagcgtta 120
gatccggcaa gcattgatgc agattttact cgcagagagt tagaaaaata tgggttggga 180
gtaacctttt cgcttggact cgatgcgcaa acagacatta gttctggtga tccggaacgc 240
gcagcgcggg gtaaagctaa attaaaagat gtcttacgtg tagcccggga ttgtggagcg 300
actcatgtct gtggaattct ctatagtgca tttcaaaaat atgcagttcc tacgaccgca 360
agaggtgtcg ccatggccgc ggacatttta ggacaggtag ctgatactgc agcacaatac 420
ggtattactt tggggttaga agtcgttaac cgttatgaga caaatgtatt gaacaccgcg 480
tcacagggtg ttgaacttat tgagcgtatt ggtcgtccca acgtaaaagt gcatttagat 540
acgtatcaca tgaatattga agagagcgat attatgagcg cgatcagaga tacgggagac 600
aggctagggt atttccatat tggcgaatct catcgtggtt acctgggttc cggaaacgtc 660
gactttactg ccgtatttag ggcgctggta ttttctggat atacgggacc gattacattt 720
gagtcattct ccagtagagt cgtaggacaa ccattagagg gaattctggc aatttggcgt 780
aatttatggg aagatggccg cgatctagct agtcacgcct tagcatatac tcgtgtccag 840
ttaaaatctg ctcaagaagc cctaaaacaa gccgagcgca gtcgcttacc gtgataa 897
<210> 72
<211> 297
<212> PRT
<213> 人工序列
<220>
<223> 变体261746
<400> 72
Met Asn Lys Leu Gly Val His Ala Leu Val Trp Glu Ala Gly Trp Ser
1 5 10 15
Arg Asp Glu Cys Ala Arg Ala Ile Ala Arg Thr Ala Glu Thr Gly Phe
20 25 30
Asp Phe Ile Glu Val Pro Ala Leu Asp Pro Ala Ser Ile Asp Ala Glu
35 40 45
Phe Thr Arg Arg Glu Leu Glu Arg His Gly Leu Gly Val Thr Phe Ser
50 55 60
Leu Gly Leu Asp Ala Gln Thr Asp Ile Ser Ser Gly Asp Pro Glu Arg
65 70 75 80
Ala Ala Arg Gly Lys Ala Lys Leu Asp Asp Val Leu Arg Val Ala Arg
85 90 95
Asp Cys Gly Gly Thr His Val Cys Gly Ile Leu Tyr Ser Ala Phe Gln
100 105 110
Lys Asn Ala Val Pro Thr Thr Arg Ala Gly Val Ala Met Ala Ala Asp
115 120 125
Ile Leu Gly Gln Val Ala Asp Thr Ala Ala Gln Tyr Gly Ile Thr Leu
130 135 140
Gly Leu Glu Val Val Asn Arg Tyr Glu Ser Asn Val Leu Asn Thr Ala
145 150 155 160
Ser Gln Gly Val Glu Leu Cys Glu Arg Ile Gly Arg Pro Asn Val Lys
165 170 175
Val His Leu Asp Thr Tyr His Met Asn Ile Glu Glu Ser Asp Ile Met
180 185 190
Ser Ala Ile Arg Asp Thr Gly Asp Arg Leu Gly Tyr Phe His Leu Gly
195 200 205
Asp Ser His Arg Gly Tyr Leu Gly Ser Gly Asn Val Asp Phe Thr Ala
210 215 220
Val Phe Arg Ala Leu Arg Phe Ser Gly Tyr Thr Gly Pro Ile Thr Phe
225 230 235 240
Glu Ser Phe Ser Ser Arg Val Val Gly Gln Pro Leu Glu Gly Ile Leu
245 250 255
Ala Ile Trp Arg Asn Leu Trp Glu Asp Ser Arg Asp Leu Ala Ser His
260 265 270
Ala Leu Ala Tyr Thr Arg Val Gln Leu Lys Ser Ala Gln Glu Ala Leu
275 280 285
Lys Gln Ala Glu Arg Ser Arg Leu Pro
290 295
<210> 73
<211> 897
<212> DNA
<213> 人工序列
<220>
<223> 变体261747的编码序列
<400> 73
atgaataagt taggtgtgca cgcattagtt tgggaagcgg gttggagtcg tgatgagtgt 60
gctcgtgcca tcgcacgcac cgcggaaacg ggatttgact tcattgaagt cccagcgtta 120
gatccgagaa gcattgatgc agagtttact cgcagagagt tagaaaaaca tgggttggga 180
gtaacctttt cgcttggact cgatgcgcaa acagacatta gttctggtga tccggaacgc 240
gcagcgcggg gtaaagctaa attaaaagat gtcttacgtg tagcccggga ttgtggagcg 300
actcatgtct gtggaattct ctatagtgca tttcaaaaat atgcagttcc tacgaccgca 360
agaggtgtcg ccatggccgc ggacatttta ggacaggtag ctgatactgc agcacaatac 420
ggtattactt tggggttaga agtcgttaac cgttatgaga caaatgtatt gaacaccgcg 480
tcacagggtg ttgaacttat tgagcgtatt ggtcgtccca acgtaaaagt gcatttagat 540
acgtatcaca tgaatattga agagagcgat attatgagcg cgatcagaga tacggcagac 600
aggctagggt atttccatat tggcgattct catcgtggtt acctgggttc cggaaacgtc 660
gactttactg ccgtatttag ggcgctggta ttttctggat atacgggacc gattacattt 720
gagtcattct ccagtagagt cgtaggacaa ccattagagg gaattctggc aatttggcgt 780
aatttatggg aagatggccg cgatctagct agtcacgcct tagcatttac tcgtgtccag 840
ttaaaatctg ctcaagaagc cctaaaacaa gccgagcgca gtcgcttacc gtgataa 897
<210> 74
<211> 297
<212> PRT
<213> 人工序列
<220>
<223> 变体261747
<400> 74
Met Asn Lys Leu Gly Val His Ala Leu Val Trp Glu Ala Gly Trp Ser
1 5 10 15
Arg Asp Glu Cys Ala Arg Ala Ile Ala Arg Thr Ala Glu Thr Gly Phe
20 25 30
Asp Phe Ile Glu Val Pro Ala Leu Asp Pro Ala Ser Ile Asp Ala Glu
35 40 45
Phe Thr Arg Arg Glu Leu Glu Arg His Gly Leu Gly Val Thr Phe Ser
50 55 60
Leu Gly Leu Asp Ala Gln Thr Asp Ile Ser Ser Gly Asp Pro Glu Arg
65 70 75 80
Ala Ala Arg Gly Lys Ala Lys Leu Asp Asp Val Leu Arg Val Ala Arg
85 90 95
Asp Cys Gly Ala Thr His Val Cys Gly Ile Leu Tyr Ser Ala Phe Gln
100 105 110
Lys Asn Ala Val Pro Thr Thr Arg Ala Gly Val Ala Met Ala Ala Asp
115 120 125
Ile Leu Gly Gln Val Ala Asp Thr Ala Ala Gln Tyr Gly Ile Thr Leu
130 135 140
Gly Leu Glu Val Val Asn Arg Tyr Glu Ser Asn Leu Leu Asn Thr Ala
145 150 155 160
Ser Gln Gly Val Glu Leu Cys Glu Arg Ile Gly Arg Pro Asn Val Lys
165 170 175
Val His Leu Asp Thr Tyr His Ala Asn Ile Glu Glu Ser Asp Ile Met
180 185 190
Ser Ala Ile Arg Asp Thr Gly Asp Arg Leu Gly Tyr Phe His Ile Gly
195 200 205
Asp Ser His Arg Gly Tyr Leu Gly Ser Gly Asn Val Asp Phe Thr Ala
210 215 220
Val Phe Arg Ala Leu Val Phe Ser Gly Tyr Thr Gly Pro Leu Thr Phe
225 230 235 240
Glu Ser Phe Ser Ser Arg Val Val Gly Gln Pro Leu Glu Gly Ile Leu
245 250 255
Ala Ile Trp Arg Asn Leu Trp Glu Asp Ser Arg Asp Leu Ala Ser His
260 265 270
Ala Leu Ala Tyr Thr Arg Val Gln Leu Lys Ser Ala Gln Glu Ala Leu
275 280 285
Lys Gln Ala Glu Arg Ser Arg Leu Pro
290 295
<210> 75
<211> 897
<212> DNA
<213> 人工序列
<220>
<223> 变体261748的编码序列
<400> 75
atgaataagt taggtgtgca cgcattagtt tgggaagcgg gttggagtcg tgatgagtgt 60
gctcgtgcca tcgcacgcac cgcggaaacg ggatttgact tcattgaagt cccagcgtta 120
gatccggcaa gcattgatgc agagtttact cgcagagagt tagaaaaata tgggttggga 180
gtaacctttt cgcttggact cgatgcgcaa acagacatta gttctggtga tccggaacgc 240
gcagcgcggg gtaaagctaa attaaaagat gtcttacgtg tagcccggga ttgtggagcg 300
actcatgtct gtggaattct ctatagtgca tttcaaaaat atgcagttcc tacgacccgt 360
agaggtgtcg ccatggccgc ggacatttta ggacaggtag ctgatactgc agcacaatac 420
ggtattactt tggggttaga agtcgttaac cgttatgaga caaatgtatt gaacaccgcg 480
tcacagggtg ttgaacttat tgagcgtatt ggtcgtccca acgtaaaagt gcatttagat 540
acgtatcaca tgaatattga agagagcgat attatgagcg cgatcagaga tacgggagac 600
aggctagggt atttccatat tggcgaatct catcgtggtt acctgggttc cggaaacgtc 660
gactttactg ccgtatttag ggcgctggta ttttctggat atacgggacc gattacattt 720
gagtcattct ccagtagagt cgtaggacaa ccattagagg gaattctggc aatttggcgt 780
aatttatggg aagattcacg cgatctagct agtcacgcct tagcatttac tcgtgtccag 840
ttaaaatctg ctcaagaagc cctaaaacaa gccgagcgca gtcgcttacc gtgataa 897
<210> 76
<211> 297
<212> PRT
<213> 人工序列
<220>
<223> 变体261748
<400> 76
Met Asn Lys Leu Gly Val His Ala Leu Val Trp Glu Ala Gly Trp Ser
1 5 10 15
Arg Asp Glu Cys Ala Arg Ala Ile Ala Arg Thr Ala Glu Thr Gly Phe
20 25 30
Asp Phe Ile Glu Val Pro Ala Leu Asp Pro Ala Ser Ile Asp Ala Glu
35 40 45
Phe Thr Arg Arg Glu Leu Glu Arg His Gly Leu Gly Val Thr Phe Ser
50 55 60
Leu Gly Leu Asp Ala Gln Thr Asp Ile Ser Ser Gly Asp Pro Glu Arg
65 70 75 80
Ala Ala Arg Gly Lys Ala Lys Leu Asp Asp Val Leu Arg Val Ala Arg
85 90 95
Asp Cys Gly Ala Thr His Val Cys Gly Ile Leu Tyr Ser Ala Phe Gln
100 105 110
Lys Asn Ala Val Pro Thr Thr Arg Ala Gly Val Ala Met Ala Ala Asp
115 120 125
Ile Leu Gly Gln Val Ala Asp Thr Ala Ala Gln Tyr Gly Ile Thr Leu
130 135 140
Gly Leu Glu Val Val Asn Arg Tyr Glu Ser Tyr Val Leu Asn Thr Ala
145 150 155 160
Ser Gln Gly Val Glu Leu Cys Glu Arg Ile Gly Arg Pro Asn Val Lys
165 170 175
Val His Leu Asp Thr Tyr His Met Asn Ile Glu Glu Ser Asp Ile Met
180 185 190
Ser Ala Ile Arg Asp Thr Gly Asp Arg Leu Gly Tyr Phe His Ile Gly
195 200 205
Asp Ser His Arg Gly Tyr Leu Gly Ser Gly Asn Leu Asp Phe Thr Ala
210 215 220
Val Phe Arg Ala Leu Val Phe Ser Gly Tyr Thr Gly Pro Ile Thr Val
225 230 235 240
Glu Ser Phe Ser Ser Arg Val Val Gly Gln Pro Leu Glu Gly Ile Leu
245 250 255
Ala Ile Trp Arg Asn Leu Trp Glu Asp Ser Arg Asp Leu Ala Ser His
260 265 270
Ala Leu Ala Tyr Thr Arg Val Gln Leu Lys Ser Ala Gln Glu Ala Leu
275 280 285
Lys Gln Ala Glu Arg Ser Arg Leu Pro
290 295
<210> 77
<211> 897
<212> DNA
<213> 人工序列
<220>
<223> 变体261749的编码序列
<400> 77
atgaataagt taggtgtgca cgcattagtt tgggaagcgg gttggagtcg tgatgagtgt 60
gctcgtgcca tcgcacgcac cgcggaaacg ggatttgact tcattgaagt cccagcgtta 120
gatccgagaa gcattgatgc agagtttact cgcagagagt tagaaaaaca tgggttggga 180
gtaacctttt cgcttggact cgatgcgcaa acagacatta gttctggtga tccggaacgc 240
gcagcgcggg gtaaagctaa attaaaagat gtcttacgtg tagcccggga ttgtggagcg 300
actcatgtct gtggaattct ctatagtgca tttcaaaaat atgcagttcc tacgacccgt 360
agaggtgtcg ccatggccgc ggacatttta ggacaggtag ctgatactgc agcacaatac 420
ggtattactt tggggttaga agtcgttaac cgttatgaga caaatgtatt gaacaccgcg 480
tcacagggtg ttgaacttat tgagcgtatt ggtcgtccca acgtaaaagt gcatttagat 540
acgtatcaca tgaatattga agagagcgat attatgagcg cgatcagaga tacggcagac 600
aggctagggt atttccatat tggcgattct catcgtggtt acctgggttc cggaaacgtc 660
gactttactg ccgtatttag ggcgctggta ttttctggat atacgggacc gattacattt 720
gagtcattct ccagtagagt cgtaggacaa ccattagagg gaattctggc aatttggcgt 780
aatttatggg aagattcacg cgatctagct agtcacgcct tagcatttac tcgtgtccag 840
ttaaaatctg ctcaagaagc cctaaaacaa gccgagcgca gtcgcttacc gtgataa 897
<210> 78
<211> 297
<212> PRT
<213> 人工序列
<220>
<223> 变体261749
<400> 78
Met Asn Lys Leu Gly Val His Ala Leu Val Trp Glu Ala Gly Trp Ser
1 5 10 15
Arg Asp Glu Cys Ala Arg Ala Ile Ala Arg Thr Ala Glu Thr Gly Phe
20 25 30
Asp Phe Ile Glu Val Pro Ala Leu Asp Pro Ala Ser Ile Asp Ala Glu
35 40 45
Phe Thr Arg Arg Glu Leu Glu Arg His Gly Leu Gly Val Thr Phe Ser
50 55 60
Leu Gly Leu Asp Ala Gln Thr Asp Ile Ser Ser Gly Asp Pro Glu Arg
65 70 75 80
Ala Ala Arg Gly Lys Ala Lys Leu Asp Asp Val Leu Arg Val Ala Arg
85 90 95
Asp Cys Gly Ala Thr His Val Cys Gly Ile Leu Tyr Ser Ala Phe Gln
100 105 110
Lys Asn Ala Val Pro Thr Thr Arg Ala Gly Val Ala Met Ala Ala Asp
115 120 125
Ile Leu Gly Gln Val Ala Asp Thr Ala Ala Gln Tyr Gly Ile Thr Leu
130 135 140
Gly Leu Glu Val Val Asn Arg Tyr Glu Ser Asn Val Leu Asn Thr Ala
145 150 155 160
Ser Gln Gly Val Glu Leu Cys Glu Arg Ile Gly Arg Pro Asn Val Lys
165 170 175
Leu His Leu Asp Thr Tyr His Met Asn Ile Glu Glu Ser Asp Ile Met
180 185 190
Ser Ala Ile Arg Asp Thr Gly Asp Arg Leu Gly Tyr Phe His Ile Gly
195 200 205
Asp Ser His Arg Gly Tyr Leu Gly Ser Gly Asn Val Asp Phe Thr Ala
210 215 220
Ile Phe Arg Ala Leu Val Phe Ser Gly Tyr Thr Gly Pro Ile Thr Leu
225 230 235 240
Glu Ser Phe Ser Ser Arg Val Val Gly Gln Pro Leu Glu Gly Ile Leu
245 250 255
Ala Ile Trp Arg Asn Leu Trp Glu Asp Ser Arg Asp Leu Ala Ser His
260 265 270
Ala Leu Ala Tyr Thr Arg Val Gln Leu Lys Ser Ala Gln Glu Ala Leu
275 280 285
Lys Gln Ala Glu Arg Ser Arg Leu Pro
290 295
<210> 79
<211> 897
<212> DNA
<213> 人工序列
<220>
<223> 变体261750的编码序列
<400> 79
atgaataagt taggtgtgca cgcattagtt tgggaagcgg gttggagtcg tgatgagtgt 60
gctcgtgcca tcgcacgcac cgcggaaacg ggatttgact tcattgaagt cccagcgtta 120
gatccgagaa gcattgatgc agattttact cgcagagagt tagaaaaaca tgggttggga 180
gtaacctttt cgcttggact cgatgcgcaa tgcgacatta gttctggtga tccggaacgc 240
gcagcgcggg gtaaagctaa attaaaagat gtcttacgtg tagcccggga ttgtggagcg 300
actcatgtct gtggaattct ctatagtgca tttcaaaaat atgcagttcc tacgacccgt 360
agaggtgtcg ccatggccgc ggacatttta ggacaggtag ctgatactgc agcacaatac 420
ggtattactt tggggttaga agtcgttaac cgttatgaga caaatgtatt gaacaccgcg 480
tcacagggtg ttgaacttat tgagcgtatt ggtcgtccca acgtaaaagt gcatttagat 540
acgtatcaca tgaatattga agagagcgat attatgagcg cgatcagaga tacgggagac 600
aggctagggt atttccatat tggcgaatct catcgtggtt acctgggttc cggaaacgtc 660
gactttactg ccgtatttag ggcgctggta ttttctggat atacgggacc gattacattt 720
gagtcattct ccagtagagt cgtaggacaa ccattagagg gaattctggc aatttggcgt 780
aatttatggg aagatggccg cgatctagct agtcacgcct tagcatatac tcgtgtccag 840
ttaaaatctg ctcaagaagc cctaaaacaa gccgagcgca gtcgcttacc gtgataa 897
<210> 80
<211> 297
<212> PRT
<213> 人工序列
<220>
<223> 变体261750
<400> 80
Met Asn Lys Leu Gly Val His Ala Leu Val Trp Glu Ala Gly Trp Ser
1 5 10 15
Arg Asp Glu Cys Ala Arg Ala Ile Ala Arg Thr Ala Glu Thr Gly Phe
20 25 30
Asp Phe Val Glu Val Pro Ala Leu Asp Pro Ala Ser Ile Asp Ala Glu
35 40 45
Phe Thr Arg Arg Glu Leu Glu Arg His Gly Leu Gly Val Thr Phe Ser
50 55 60
Leu Gly Leu Asp Ala Gln Thr Asp Ile Ser Ser Gly Asp Pro Glu Arg
65 70 75 80
Ala Ala Arg Gly Lys Ala Lys Leu Asp Asp Val Leu Arg Val Ala Arg
85 90 95
Asp Cys Gly Ala Thr His Val Cys Gly Ile Leu Tyr Ser Ala Phe Gln
100 105 110
Lys Asn Ala Val Pro Thr Thr Arg Ala Gly Val Ala Met Ala Ala Asp
115 120 125
Ile Leu Gly Gln Val Ala Asp Thr Ala Ala Gln Tyr Gly Val Thr Leu
130 135 140
Gly Leu Glu Val Val Asn Arg Tyr Glu Ser Asn Val Leu Asn Thr Ala
145 150 155 160
Ser Gln Gly Val Glu Leu Cys Glu Arg Ile Gly Arg Pro Asn Val Lys
165 170 175
Val His Leu Asp Thr Tyr His Met Asn Ile Glu Glu Ser Asp Ile Met
180 185 190
Ser Ala Ile Arg Asp Thr Gly Asp Arg Leu Gly Tyr Phe His Ile Gly
195 200 205
Asp Ser His Arg Gly Tyr Leu Gly Ser Gly Asn Val Asp Phe Thr Ala
210 215 220
Val Phe Arg Ala Leu Val Phe Ser Gly Tyr Thr Gly Pro Ile Thr Phe
225 230 235 240
Glu Ser Phe Ser Ser Arg Val Val Gly Gln Pro Leu Glu Gly Ile Leu
245 250 255
Ala Ile Trp Arg Asn Leu Trp Glu Asp Ser Arg Asp Leu Ala Ser His
260 265 270
Gly Leu Ala Tyr Thr Arg Val Gln Leu Lys Ser Ala Gln Glu Ala Leu
275 280 285
Lys Gln Ala Glu Arg Ser Arg Leu Pro
290 295
<210> 81
<211> 897
<212> DNA
<213> 人工序列
<220>
<223> 变体261751的编码序列
<400> 81
atgaataagt taggtgtgca cgcattagtt tgggaagcgg gttggagtcg tgatgagtgt 60
gctcgtgcca tcgcacgcac cgcggaaacg ggatttgact tcattgaagt cccagcgtta 120
gatccggcaa gcattgatgc agattttact cgcagagagt tagaaaaaca tgggttggga 180
gtaacctttt cgcttggact cgatgcgcaa tgcgacatta gttctggtga tccggaacgc 240
gcagcgcggg gtaaagctaa attaaaagat gtcttacgtg tagcccggga ttgtggagcg 300
actcatgtct gtggaattct ctatagtgca tttcaaaaat atgcagttcc tacgacccgt 360
agaggtgtcg ccatggccgc ggacatttta ggacaggtag ctgatactgc agcacaatac 420
ggtattactt tggggttaga agtcgttaac cgttatgaga caaatgtatt gaacaccgcg 480
tcacagggtg ttgaacttat tgagcgtatt ggtcgtccca acgtaaaagt gcatttagat 540
acgtatcaca tgaatattga agagagcgat attatgagcg cgatcagaga tacgggagac 600
aggctagggt atttccatat tggcgaatct catcgtggtt acctgggttc cggaaacgtc 660
gactttactg ccgtatttag ggcgctggta ttttctggat atacgggacc gattacattt 720
gagtcattct ccagtagagt cgtaggacaa ccattagagg gaattctggc aatttggcgt 780
aatttatggg aagatggccg cgatctagct agtcacgcct tagcatttac tcgtgtccag 840
ttaaaatctg ctcaagaagc cctaaaacaa gccgagcgca gtcgcttacc gtgataa 897
<210> 82
<211> 297
<212> PRT
<213> 人工序列
<220>
<223> 变体261751
<400> 82
Met Asn Lys Leu Gly Val His Ala Leu Val Trp Glu Ala Gly Trp Ser
1 5 10 15
Arg Asp Glu Cys Ala Arg Ala Ile Ala Arg Thr Ala Glu Thr Gly Phe
20 25 30
Asp Phe Ile Glu Val Pro Ala Leu Asp Pro Ala Ser Ile Asp Ala Glu
35 40 45
Phe Thr Arg Arg Glu Leu Glu Arg His Gly Leu Gly Val Thr Phe Ser
50 55 60
Leu Gly Leu Asp Ala Gln Thr Asp Ile Ser Ser Gly Asp Pro Glu Arg
65 70 75 80
Ala Ala Arg Gly Lys Ala Lys Leu Asp Asp Val Leu Arg Val Ala Arg
85 90 95
Asp Cys Gly Ala Thr His Val Cys Gly Ile Leu Tyr Ser Ala Phe Gln
100 105 110
Lys Asn Ala Val Pro Thr Thr Arg Ala Gly Val Ala Met Ala Ala Asp
115 120 125
Ile Leu Gly Gln Val Ala Asp Thr Ala Ala Gln Tyr Gly Ile Thr Leu
130 135 140
Gly Leu Glu Val Val Asn Arg Tyr Glu Ser Asn Val Leu Asn Thr Ala
145 150 155 160
Ser Gln Gly Val Glu Leu Cys Glu Arg Ile Gly Arg Pro Asn Val Lys
165 170 175
Val His Leu Asp Thr Tyr His Met Asn Ile Glu Glu Ser Asp Ile Met
180 185 190
Ser Ala Ile Arg Asp Thr Gly Asp Arg Leu Gly Tyr Phe His Ile Gly
195 200 205
Asp Ser His Arg Gly Tyr Leu Gly Thr Gly His Val Asp Phe Thr Ala
210 215 220
Val Phe Arg Ala Leu Val Phe Ser Gly Tyr Thr Gly Pro Leu Thr Phe
225 230 235 240
Glu Ser Phe Ser Ser Arg Val Val Gly Gln Pro Leu Glu Gly Ile Leu
245 250 255
Ala Ile Trp Arg Asn Leu Trp Glu Asp Ser Arg Asp Leu Ala Ser His
260 265 270
Ala Leu Ala Tyr Thr Arg Val Gln Leu Lys Ser Ala Gln Glu Ala Leu
275 280 285
Lys Gln Ala Glu Arg Ser Arg Leu Pro
290 295
<210> 83
<211> 897
<212> DNA
<213> 人工序列
<220>
<223> 变体261752的编码序列
<400> 83
atgaataagt taggtgtgca cgcattagtt tgggaagcgg gttggagtcg tgatgagtgt 60
gctcgtgcca tcgcacgcac cgcggaaacg ggatttgact tcattgaagt cccagcgtta 120
gatccgagaa gcattgatgc agattttact cgcagagagt tagaaaaaca tgggttggga 180
gtaacctttt cgcttggact cgatgcgcaa tgcgacatta gttctggtga tccggaacgc 240
gcagcgcggg gtaaagctaa attaaaagat gtcttacgtg tagcccggga ttgtggagcg 300
actcatgtct gtggaattct ctatagtgca tttcaaaaat atgcagttcc tacgaccgca 360
agaggtgtcg ccatggccgc ggacatttta ggacaggtag ctgatactgc agcacaatac 420
ggtattactt tggggttaga agtcgttaac cgttatgaga caaatgtatt gaacaccgcg 480
tcacagggtg ttgaacttat tgagcgtatt ggtcgtccca acgtaaaagt gcatttagat 540
acgtatcaca tgaatattga agagagcgat attatgagcg cgatcagaga tacgggagac 600
aggctagggt atttccatat tggcgattct catcgtggtt acctgggttc cggaaacgtc 660
gactttactg ccgtatttag ggcgctggta ttttctggat atacgggacc gattacattt 720
gagtcattct ccagtagagt cgtaggacaa ccattagagg gaattctggc aatttggcgt 780
aatttatggg aagatggccg cgatctagct agtcacgcct tagcatatac tcgtgtccag 840
ttaaaatctg ctcaagaagc cctaaaacaa gccgagcgca gtcgcttacc gtgataa 897
<210> 84
<211> 297
<212> PRT
<213> 人工序列
<220>
<223> 变体261752
<400> 84
Met Asn Lys Leu Gly Val His Ala Leu Val Trp Glu Ala Gly Trp Ser
1 5 10 15
Arg Asp Glu Cys Ala Arg Ala Ile Ala Arg Thr Ala Glu Thr Gly Phe
20 25 30
Asp Phe Ile Glu Val Pro Ala Leu Asp Pro Ala Ser Ile Asp Ala Glu
35 40 45
Phe Thr Arg Arg Glu Leu Glu Arg His Gly Leu Gly Val Thr Phe Ser
50 55 60
Leu Gly Leu Asp Ala Gln Thr Asp Ile Ser Ser Gly Asp Pro Glu Arg
65 70 75 80
Ala Ala Arg Gly Lys Ala Lys Leu Asp Asp Val Leu Arg Val Ala Arg
85 90 95
Asp Cys Gly Ala Thr His Val Cys Gly Ile Leu Tyr Ser Ala Phe Gln
100 105 110
Lys Asn Ala Val Pro Thr Thr Arg Ala Gly Val Ala Met Ala Ala Asp
115 120 125
Ile Leu Gly Gln Val Ala Asp Thr Ala Ala Gln Tyr Gly Ile Thr Leu
130 135 140
Gly Leu Glu Val Val Asn Arg Phe Glu Ser Asn Val Leu Asn Thr Ala
145 150 155 160
Ser Gln Gly Val Glu Leu Cys Glu Arg Ile Gly Arg Pro Asn Val Lys
165 170 175
Val His Leu Asp Thr Tyr His Met Asn Ile Glu Glu Ser Asp Ile Met
180 185 190
Ser Ala Ile Arg Asp Thr Gly Asp Arg Leu Gly Tyr Phe His Ile Gly
195 200 205
Asp Ser His Arg Gly Tyr Leu Gly Ser Gly Asn Leu Asp Phe Thr Ala
210 215 220
Val Phe Arg Ala Leu Val Phe Ser Gly Tyr Thr Gly Pro Ile Thr Phe
225 230 235 240
Glu Ser Phe Ser Ser Arg Val Val Gly Gln Pro Leu Glu Gly Ile Leu
245 250 255
Ala Ile Trp Arg Asn Leu Trp Glu Asp Ser Arg Asp Leu Ala Ser His
260 265 270
Ala Leu Ala Tyr Leu Arg Val Gln Leu Lys Ser Ala Gln Glu Ala Leu
275 280 285
Lys Gln Ala Glu Arg Ser Arg Leu Pro
290 295
<210> 85
<211> 897
<212> DNA
<213> 人工序列
<220>
<223> 变体261753的编码序列
<400> 85
atgaataagt taggtgtgca cgcattagtt tgggaagcgg gttggagtcg tgatgagtgt 60
gctcgtgcca tcgcacgcac cgcggaaacg ggatttgact tcattgaagt cccagcgtta 120
gatccggcaa gcattgatgc agagtttact cgcagagagt tagaaaaata tgggttggga 180
gtaacctttt cgcttggact cgatgcgcaa tgcgacatta gttctggtga tccggaacgc 240
gcagcgcggg gtaaagctaa attaaaagat gtcttacgtg tagcccggga ttgtggagcg 300
actcatgtct gtggaattct ctatagtgca tttcaaaaat atgcagttcc tacgacccgt 360
agaggtgtcg ccatggccgc ggacatttta ggacaggtag ctgatactgc agcacaatac 420
ggtattactt tggggttaga agtcgttaac cgttatgaga caaatgtatt gaacaccgcg 480
tcacagggtg ttgaacttat tgagcgtatt ggtcgtccca acgtaaaagt gcatttagat 540
acgtatcaca tgaatattga agagagcgat attatgagcg cgatcagaga tacggcagac 600
aggctagggt atttccatat tggcgattct catcgtggtt acctgggttc cggaaacgtc 660
gactttactg ccgtatttag ggcgctggta ttttctggat atacgggacc gattacattt 720
gagtcattct ccagtagagt cgtaggacaa ccattagagg gaattctggc aatttggcgt 780
aatttatggg aagattcacg cgatctagct agtcacgcct tagcatatac tcgtgtccag 840
ttaaaatctg ctcaagaagc cctaaaacaa gccgagcgca gtcgcttacc gtgataa 897
<210> 86
<211> 297
<212> PRT
<213> 人工序列
<220>
<223> 变体261753
<400> 86
Met Asn Lys Leu Gly Val His Ala Leu Val Trp Glu Ala Gly Trp Ser
1 5 10 15
Arg Asp Glu Cys Ala Arg Ala Ile Ala Arg Thr Ala Glu Thr Gly Phe
20 25 30
Asp Phe Ile Glu Leu Pro Ala Leu Asp Pro Ala Ser Ile Asp Ala Glu
35 40 45
Phe Thr Arg Arg Glu Leu Glu Arg His Gly Leu Gly Val Thr Phe Ser
50 55 60
Leu Gly Leu Asp Ala Gln Thr Asp Ile Ser Ser Gly Asp Pro Glu Arg
65 70 75 80
Ala Ala Arg Gly Lys Ala Lys Leu Asp Asp Val Leu Arg Val Ala Arg
85 90 95
Asp Cys Gly Ala Thr His Val Cys Gly Ile Leu Tyr Ser Ala Phe Gln
100 105 110
Lys Asn Ala Val Pro Thr Thr Arg Ala Gly Val Ala Met Ala Ala Asp
115 120 125
Ile Leu Gly Gln Val Ala Asp Thr Ala Ala Gln Tyr Gly Val Thr Leu
130 135 140
Gly Leu Glu Val Val Asn Arg Tyr Glu Ser Asn Leu Leu Asn Thr Ala
145 150 155 160
Ser Gln Gly Val Glu Leu Cys Glu Arg Ile Gly Arg Pro Asn Val Lys
165 170 175
Val His Leu Asp Thr Tyr His Met Asn Ile Glu Glu Ser Asp Ile Met
180 185 190
Ser Ala Ile Arg Asp Thr Gly Asp Arg Leu Gly Tyr Phe His Ile Gly
195 200 205
Asp Ser His Arg Gly Tyr Leu Gly Ser Gly Asn Val Asp Phe Thr Ala
210 215 220
Val Phe Arg Ala Leu Val Phe Ser Gly Tyr Thr Gly Pro Ile Thr Phe
225 230 235 240
Glu Ser Phe Ser Ser Arg Val Val Gly Gln Pro Leu Glu Gly Ile Leu
245 250 255
Ala Ile Trp Arg Asn Leu Trp Glu Asp Ser Arg Asp Leu Ala Ser His
260 265 270
Ala Leu Ala Tyr Thr Arg Val Gln Leu Lys Ser Ala Gln Glu Ala Leu
275 280 285
Lys Gln Ala Glu Arg Ser Arg Leu Pro
290 295
<210> 87
<211> 897
<212> DNA
<213> 人工序列
<220>
<223> 变体261754的编码序列
<400> 87
atgaataagt taggtgtgca cgcattagtt tgggaagcgg gttggagtcg tgatgagtgt 60
gctcgtgcca tcgcacgcac cgcggaaacg ggatttgact tcattgaagt cccagcgtta 120
gatccggcaa gcattgatgc agagtttact cgcagagagt tagaaaaata tgggttggga 180
gtaacctttt cgcttggact cgatgcgcaa acagacatta gttctggtga tccggaacgc 240
gcagcgcggg gtaaagctaa attaaaagat gtcttacgtg tagcccggga ttgtggagcg 300
actcatgtct gtggaattct ctatagtgca tttcaaaaat atgcagttcc tacgaccgca 360
agaggtgtcg ccatggccgc ggacatttta ggacaggtag ctgatactgc agcacaatac 420
ggtattactt tggggttaga agtcgttaac cgttatgaga caaatgtatt gaacaccgcg 480
tcacagggtg ttgaacttat tgagcgtatt ggtcgtccca acgtaaaagt gcatttagat 540
acgtatcaca tgaatattga agagagcgat attatgagcg cgatcagaga tacggcagac 600
aggctagggt atttccatat tggcgattct catcgtggtt acctgggttc cggaaacgtc 660
gactttactg ccgtatttag ggcgctggta ttttctggat atacgggacc gattacattt 720
gagtcattct ccagtagagt cgtaggacaa ccattagagg gaattctggc aatttggcgt 780
aatttatggg aagattcacg cgatctagct agtcacgcct tagcatatac tcgtgtccag 840
ttaaaatctg ctcaagaagc cctaaaacaa gccgagcgca gtcgcttacc gtgataa 897
<210> 88
<211> 297
<212> PRT
<213> 人工序列
<220>
<223> 变体261754
<400> 88
Met Asn Lys Leu Gly Val His Ala Leu Val Trp Glu Ala Gly Trp Ser
1 5 10 15
Arg Asp Glu Cys Ala Arg Ala Ile Ala Arg Thr Ala Glu Thr Gly Phe
20 25 30
Asp Phe Ile Glu Val Pro Ala Leu Asp Pro Ala Ser Ile Asp Ala Glu
35 40 45
Phe Thr Arg Arg Glu Leu Glu Arg His Gly Leu Gly Val Thr Phe Ser
50 55 60
Leu Gly Leu Asp Ala Gln Thr Asp Ile Ser Ser Gly Asp Pro Glu Arg
65 70 75 80
Ala Ala Arg Gly Lys Ala Lys Leu Asp Asp Val Leu Arg Val Ala Arg
85 90 95
Asp Cys Gly Ala Thr His Val Cys Gly Ile Leu Tyr Ser Ala Phe Gln
100 105 110
Lys Asn Ala Val Pro Thr Thr Arg Ala Gly Val Ala Met Ala Ala Asp
115 120 125
Ile Leu Gly Gln Val Ala Asp Thr Ala Ala Gln Tyr Gly Ile Thr Leu
130 135 140
Gly Leu Glu Val Val Asn Arg Tyr Glu Ser Asn Val Leu Asn Thr Ala
145 150 155 160
Ser Gln Gly Val Glu Leu Cys Glu Arg Ile Gly Arg Pro Asn Val Lys
165 170 175
Val His Leu Asp Thr Tyr His Met Asn Ile Glu Glu Ser Asp Ile Met
180 185 190
Ser Ala Ile Arg Asp Thr Gly Asp Arg Leu Gly Tyr Phe His Ile Gly
195 200 205
Asp Ser His Arg Gly Tyr Leu Gly Ser Gly Asn Val Asp Phe Thr Ala
210 215 220
Val Phe Arg Ala Leu Val Phe Ser Gly Tyr Thr Gly Pro Ile Thr Met
225 230 235 240
Glu Cys Phe Ser Ser Arg Val Val Gly Gln Pro Leu Glu Gly Ile Leu
245 250 255
Ala Ile Trp Arg Asn Leu Trp Glu Asp Ser Arg Asp Val Ala Ser His
260 265 270
Ala Leu Ala Tyr Thr Arg Val Gln Leu Lys Ser Ala Gln Glu Ala Leu
275 280 285
Lys Gln Ala Glu Arg Ser Arg Leu Pro
290 295
<210> 89
<211> 897
<212> DNA
<213> 人工序列
<220>
<223> 变体277285的编码序列
<400> 89
atgaataagt taggtgtgca cgcattagtt tgggaagcgg gttggagtcg tgatgagtgt 60
gctcgtgcca tcgcacgcac cgcggaaacg ggatttgact tcattgaagt cccagcgtta 120
gatccggcaa gcattgatgc agagtttact cgcagagagt tagaacgcca tgggttggga 180
gtaacctttt cgcttggact cgatgcgcaa acagacatta gttctggtga tccggaacgc 240
gcagcgcggg gtaaagctaa attaaaagat gtcttacgtg tagcccggga ttgtggagcg 300
actcatgtct gtggaattct ctatagtgca tttcaaaaaa atgcagttcc tacgacccgt 360
gcgggtgtcg ccatggccgc ggacatttta ggacaggtag ctgatactgc agcacaatac 420
ggtattactt tggggttaga agtcgttaac cgttatgagt caaatgtatt gaacaccgcg 480
tcacagggtg ttgaactttg cgagcgtatt ggtcgtccca acgtaaaagt gcatttagat 540
acgtatcaca tgaatattga agagagcgat attatgagcg cgatcagaga tacgggagac 600
aggctagggt atttccatat tggcgattct catcgtggtt acctgggttc cggaaacgtc 660
gactttactg ccgtatttag ggcgctggta ttttctggat atacgggacc gattacattt 720
gagtcattct ccagtagagt cgtaggacaa ccattagagg gaattctggc aatttggcgt 780
aatttatggg aagattcccg cgatctagct agtcacgcct tagcatatac tcgtgtccag 840
ttaaaatctg ctcaagaagc cctaaaacaa gccgagcgca gtcgcttacc gtgataa 897
<210> 90
<211> 297
<212> PRT
<213> 人工序列
<220>
<223> 变体277285
<400> 90
Met Asn Lys Leu Gly Val His Ala Leu Val Trp Glu Ala Gly Trp Ser
1 5 10 15
Arg Asp Glu Cys Ala Arg Ala Ile Ala Arg Thr Ala Glu Thr Gly Phe
20 25 30
Asp Phe Ile Glu Val Pro Ala Leu Asp Pro Ala Ser Ile Asp Ala Glu
35 40 45
Phe Thr Arg Arg Glu Leu Glu Arg His Gly Leu Gly Val Thr Phe Ser
50 55 60
Leu Gly Leu Asp Ala Gln Thr Asp Ile Ser Ser Gly Asp Pro Glu Arg
65 70 75 80
Ala Ala Arg Gly Lys Ala Lys Leu Lys Asp Val Leu Arg Val Ala Arg
85 90 95
Asp Cys Gly Ala Thr His Val Cys Gly Ile Leu Tyr Ser Ala Phe Gln
100 105 110
Lys Asn Ala Val Pro Thr Thr Arg Ala Gly Val Ala Met Ala Ala Asp
115 120 125
Ile Leu Gly Gln Val Ala Asp Thr Ala Ala Gln Tyr Gly Ile Thr Leu
130 135 140
Gly Leu Glu Val Val Asn Arg Tyr Glu Ser Asn Val Leu Asn Thr Ala
145 150 155 160
Ser Gln Gly Val Glu Leu Cys Glu Arg Ile Gly Arg Pro Asn Val Lys
165 170 175
Val His Leu Asp Thr Tyr His Met Asn Ile Glu Glu Ser Asp Ile Met
180 185 190
Ser Ala Ile Arg Asp Thr Gly Asp Arg Leu Gly Tyr Phe His Ile Gly
195 200 205
Asp Ser His Arg Gly Tyr Leu Gly Ser Gly Asn Val Asp Phe Thr Ala
210 215 220
Val Phe Arg Ala Leu Val Phe Ser Gly Tyr Thr Gly Pro Ile Thr Phe
225 230 235 240
Glu Ser Phe Ser Ser Arg Val Val Gly Gln Pro Leu Glu Gly Ile Leu
245 250 255
Ala Ile Trp Arg Asn Leu Trp Glu Asp Ser Arg Asp Leu Ala Ser His
260 265 270
Ala Leu Ala Tyr Thr Arg Val Gln Leu Lys Ser Ala Gln Glu Ala Leu
275 280 285
Lys Gln Ala Glu Arg Ser Arg Leu Pro
290 295
<210> 91
<211> 897
<212> DNA
<213> 人工序列
<220>
<223> 变体277286的编码序列
<400> 91
atgaataagt taggtgtgca cgcattagtt tgggaagcgg gttggagtcg tgatgagtgt 60
gctcgtgcca tcgcacgcac cgcggaaacg ggatttgact tcattgaagt cccagcgtta 120
gatccggcaa gcattgatgc agagtttact cgcagagagt tagaacgcca tgggttggga 180
gtaacctttt cgcttggact cgatgcgcaa acagacatta gttctggtga tccggaacgc 240
gcagcgcggg gtaaagctaa attagacgat gtcttacgtg tagcccggga ttgtggagcg 300
actcatgtct gtggaattct ctatagtgca tttcaaaaaa atgcagttcc tacgacccgt 360
gcgggtgtcg ccatggccgc ggacatttta ggacaggtag ctgatactgc agcacaatac 420
ggtattactt tggggttaga agtcgttaac cgttatgaga caaatgtatt gaacaccgcg 480
tcacagggtg ttgaactttg cgagcgtatt ggtcgtccca acgtaaaagt gcatttagat 540
acgtatcaca tgaatattga agagagcgat attatgagcg cgatcagaga tacgggagac 600
aggctagggt atttccatat tggcgattct catcgtggtt acctgggttc cggaaacgtc 660
gactttactg ccgtatttag ggcgctggta ttttctggat atacgggacc gattacattt 720
gagtcattct ccagtagagt cgtaggacaa ccattagagg gaattctggc aatttggcgt 780
aatttatggg aagattcccg cgatctagct agtcacgcct tagcatatac tcgtgtccag 840
ttaaaatctg ctcaagaagc cctaaaacaa gccgagcgca gtcgcttacc gtgataa 897
<210> 92
<211> 297
<212> PRT
<213> 人工序列
<220>
<223> 变体277286
<400> 92
Met Asn Lys Leu Gly Val His Ala Leu Val Trp Glu Ala Gly Trp Ser
1 5 10 15
Arg Asp Glu Cys Ala Arg Ala Ile Ala Arg Thr Ala Glu Thr Gly Phe
20 25 30
Asp Phe Ile Glu Val Pro Ala Leu Asp Pro Ala Ser Ile Asp Ala Glu
35 40 45
Phe Thr Arg Arg Glu Leu Glu Arg His Gly Leu Gly Val Thr Phe Ser
50 55 60
Leu Gly Leu Asp Ala Gln Thr Asp Ile Ser Ser Gly Asp Pro Glu Arg
65 70 75 80
Ala Ala Arg Gly Lys Ala Lys Leu Asp Asp Val Leu Arg Val Ala Arg
85 90 95
Asp Cys Gly Ala Thr His Val Cys Gly Ile Leu Tyr Ser Ala Phe Gln
100 105 110
Lys Asn Ala Val Pro Thr Thr Arg Ala Gly Val Ala Met Ala Ala Asp
115 120 125
Ile Leu Gly Gln Val Ala Asp Thr Ala Ala Gln Tyr Gly Ile Thr Leu
130 135 140
Gly Leu Glu Val Val Asn Arg Tyr Glu Thr Asn Val Leu Asn Thr Ala
145 150 155 160
Ser Gln Gly Val Glu Leu Cys Glu Arg Ile Gly Arg Pro Asn Val Lys
165 170 175
Val His Leu Asp Thr Tyr His Met Asn Ile Glu Glu Ser Asp Ile Met
180 185 190
Ser Ala Ile Arg Asp Thr Gly Asp Arg Leu Gly Tyr Phe His Ile Gly
195 200 205
Asp Ser His Arg Gly Tyr Leu Gly Ser Gly Asn Val Asp Phe Thr Ala
210 215 220
Val Phe Arg Ala Leu Val Phe Ser Gly Tyr Thr Gly Pro Ile Thr Phe
225 230 235 240
Glu Ser Phe Ser Ser Arg Val Val Gly Gln Pro Leu Glu Gly Ile Leu
245 250 255
Ala Ile Trp Arg Asn Leu Trp Glu Asp Ser Arg Asp Leu Ala Ser His
260 265 270
Ala Leu Ala Tyr Thr Arg Val Gln Leu Lys Ser Ala Gln Glu Ala Leu
275 280 285
Lys Gln Ala Glu Arg Ser Arg Leu Pro
290 295
<210> 93
<211> 897
<212> DNA
<213> 人工序列
<220>
<223> 变体277287的编码序列
<400> 93
atgaataagt taggtgtgca cgcattagtt tgggaagcgg gttggagtcg tgatgagtgt 60
gctcgtgcca tcgcacgcac cgcggaaacg ggatttgact tcattgaagt cccagcgtta 120
gatccggcaa gcattgatgc agagtttact cgcagagagt tagaacgcca tgggttggga 180
gtaacctttt cgcttggact cgatgcgcaa acagacatta gttctggtga tccggaacgc 240
gcagcgcggg gtaaagctaa attagacgat gtcttacgtg tagcccggga ttgtggagcg 300
actcatgtct gtggaattct ctatagtgca tttcaaaaaa atgcagttcc tacgacccgt 360
gcgggtgtcg ccatggccgc ggacatttta ggacaggtag ctgatactgc agcacaatac 420
ggtattactt tggggttaga agtcgttaac cgttatgagt caaatgtatt gaacaccgcg 480
tcacagggtg ttgaacttat tgagcgtatt ggtcgtccca acgtaaaagt gcatttagat 540
acgtatcaca tgaatattga agagagcgat attatgagcg cgatcagaga tacgggagac 600
aggctagggt atttccatat tggcgattct catcgtggtt acctgggttc cggaaacgtc 660
gactttactg ccgtatttag ggcgctggta ttttctggat atacgggacc gattacattt 720
gagtcattct ccagtagagt cgtaggacaa ccattagagg gaattctggc aatttggcgt 780
aatttatggg aagattcccg cgatctagct agtcacgcct tagcatatac tcgtgtccag 840
ttaaaatctg ctcaagaagc cctaaaacaa gccgagcgca gtcgcttacc gtgataa 897
<210> 94
<211> 297
<212> PRT
<213> 人工序列
<220>
<223> 变体277287
<400> 94
Met Asn Lys Leu Gly Val His Ala Leu Val Trp Glu Ala Gly Trp Ser
1 5 10 15
Arg Asp Glu Cys Ala Arg Ala Ile Ala Arg Thr Ala Glu Thr Gly Phe
20 25 30
Asp Phe Ile Glu Val Pro Ala Leu Asp Pro Ala Ser Ile Asp Ala Glu
35 40 45
Phe Thr Arg Arg Glu Leu Glu Arg His Gly Leu Gly Val Thr Phe Ser
50 55 60
Leu Gly Leu Asp Ala Gln Thr Asp Ile Ser Ser Gly Asp Pro Glu Arg
65 70 75 80
Ala Ala Arg Gly Lys Ala Lys Leu Asp Asp Val Leu Arg Val Ala Arg
85 90 95
Asp Cys Gly Ala Thr His Val Cys Gly Ile Leu Tyr Ser Ala Phe Gln
100 105 110
Lys Asn Ala Val Pro Thr Thr Arg Ala Gly Val Ala Met Ala Ala Asp
115 120 125
Ile Leu Gly Gln Val Ala Asp Thr Ala Ala Gln Tyr Gly Ile Thr Leu
130 135 140
Gly Leu Glu Val Val Asn Arg Tyr Glu Ser Asn Val Leu Asn Thr Ala
145 150 155 160
Ser Gln Gly Val Glu Leu Ile Glu Arg Ile Gly Arg Pro Asn Val Lys
165 170 175
Val His Leu Asp Thr Tyr His Met Asn Ile Glu Glu Ser Asp Ile Met
180 185 190
Ser Ala Ile Arg Asp Thr Gly Asp Arg Leu Gly Tyr Phe His Ile Gly
195 200 205
Asp Ser His Arg Gly Tyr Leu Gly Ser Gly Asn Val Asp Phe Thr Ala
210 215 220
Val Phe Arg Ala Leu Val Phe Ser Gly Tyr Thr Gly Pro Ile Thr Phe
225 230 235 240
Glu Ser Phe Ser Ser Arg Val Val Gly Gln Pro Leu Glu Gly Ile Leu
245 250 255
Ala Ile Trp Arg Asn Leu Trp Glu Asp Ser Arg Asp Leu Ala Ser His
260 265 270
Ala Leu Ala Tyr Thr Arg Val Gln Leu Lys Ser Ala Gln Glu Ala Leu
275 280 285
Lys Gln Ala Glu Arg Ser Arg Leu Pro
290 295
<210> 95
<211> 897
<212> DNA
<213> 人工序列
<220>
<223> 变体277288的编码序列
<400> 95
atgaataagt taggtgtgca cgcattagtt tgggaagcgg gttggagtcg tgatgagtgt 60
gctcgtgcca tcgcacgcac cgcggaaacg ggatttgact tcattgaagt cccagcgtta 120
gatccggcaa gcattgatgc agagtttact cgcagagagt tagaacgcca tgggttggga 180
gtaacctttt cgcttggact cgatgcgcaa acagacatta gttctggtga tccggaacgc 240
gcagcgcggg gtaaagctaa attaaaagat gtcttacgtg tagcccggga ttgtggagcg 300
actcatgtct gtggaattct ctatagtgca tttcaaaaaa atgcagttcc tacgacccgt 360
gcgggtgtcg ccatggccgc ggacatttta ggacaggtag ctgatactgc agcacaatac 420
ggtattactt tggggttaga agtcgttaac cgttatgaga caaatgtatt gaacaccgcg 480
tcacagggtg ttgaactttg cgagcgtatt ggtcgtccca acgtaaaagt gcatttagat 540
acgtatcaca tgaatattga agagagcgat attatgagcg cgatcagaga tacgggagac 600
aggctagggt atttccatat tggcgattct catcgtggtt acctgggttc cggaaacgtc 660
gactttactg ccgtatttag ggcgctggta ttttctggat atacgggacc gattacattt 720
gagtcattct ccagtagagt cgtaggacaa ccattagagg gaattctggc aatttggcgt 780
aatttatggg aagattcccg cgatctagct agtcacgcct tagcatatac tcgtgtccag 840
ttaaaatctg ctcaagaagc cctaaaacaa gccgagcgca gtcgcttacc gtgataa 897
<210> 96
<211> 297
<212> PRT
<213> 人工序列
<220>
<223> 变体277288
<400> 96
Met Asn Lys Leu Gly Val His Ala Leu Val Trp Glu Ala Gly Trp Ser
1 5 10 15
Arg Asp Glu Cys Ala Arg Ala Ile Ala Arg Thr Ala Glu Thr Gly Phe
20 25 30
Asp Phe Ile Glu Val Pro Ala Leu Asp Pro Ala Ser Ile Asp Ala Glu
35 40 45
Phe Thr Arg Arg Glu Leu Glu Arg His Gly Leu Gly Val Thr Phe Ser
50 55 60
Leu Gly Leu Asp Ala Gln Thr Asp Ile Ser Ser Gly Asp Pro Glu Arg
65 70 75 80
Ala Ala Arg Gly Lys Ala Lys Leu Lys Asp Val Leu Arg Val Ala Arg
85 90 95
Asp Cys Gly Ala Thr His Val Cys Gly Ile Leu Tyr Ser Ala Phe Gln
100 105 110
Lys Asn Ala Val Pro Thr Thr Arg Ala Gly Val Ala Met Ala Ala Asp
115 120 125
Ile Leu Gly Gln Val Ala Asp Thr Ala Ala Gln Tyr Gly Ile Thr Leu
130 135 140
Gly Leu Glu Val Val Asn Arg Tyr Glu Thr Asn Val Leu Asn Thr Ala
145 150 155 160
Ser Gln Gly Val Glu Leu Cys Glu Arg Ile Gly Arg Pro Asn Val Lys
165 170 175
Val His Leu Asp Thr Tyr His Met Asn Ile Glu Glu Ser Asp Ile Met
180 185 190
Ser Ala Ile Arg Asp Thr Gly Asp Arg Leu Gly Tyr Phe His Ile Gly
195 200 205
Asp Ser His Arg Gly Tyr Leu Gly Ser Gly Asn Val Asp Phe Thr Ala
210 215 220
Val Phe Arg Ala Leu Val Phe Ser Gly Tyr Thr Gly Pro Ile Thr Phe
225 230 235 240
Glu Ser Phe Ser Ser Arg Val Val Gly Gln Pro Leu Glu Gly Ile Leu
245 250 255
Ala Ile Trp Arg Asn Leu Trp Glu Asp Ser Arg Asp Leu Ala Ser His
260 265 270
Ala Leu Ala Tyr Thr Arg Val Gln Leu Lys Ser Ala Gln Glu Ala Leu
275 280 285
Lys Gln Ala Glu Arg Ser Arg Leu Pro
290 295
<210> 97
<211> 897
<212> DNA
<213> 人工序列
<220>
<223> 变体277289的编码序列
<400> 97
atgaataagt taggtgtgca cgcattagtt tgggaagcgg gttggagtcg tgatgagtgt 60
gctcgtgcca tcgcacgcac cgcggaaacg ggatttgact tcattgaagt cccagcgtta 120
gatccggcaa gcattgatgc agagtttact cgcagagagt tagaacgcca tgggttggga 180
gtaacctttt cgcttggact cgatgcgcaa acagacatta gttctggtga tccggaacgc 240
gcagcgcggg gtaaagctaa attagacgat gtcttacgtg tagcccggga ttgtggagcg 300
actcatgtct gtggaattct ctatagtgca tttcaaaaaa atgcagttcc tacgacccgt 360
gcgggtgtcg ccatggccgc ggacatttta ggacaggtag ctgatactgc agcacaatac 420
ggtattactt tggggttaga agtcgttaac cgttatgaga caaatgtatt gaacaccgcg 480
tcacagggtg ttgaacttat tgagcgtatt ggtcgtccca acgtaaaagt gcatttagat 540
acgtatcaca tgaatattga agagagcgat attatgagcg cgatcagaga tacgggagac 600
aggctagggt atttccatat tggcgattct catcgtggtt acctgggttc cggaaacgtc 660
gactttactg ccgtatttag ggcgctggta ttttctggat atacgggacc gattacattt 720
gagtcattct ccagtagagt cgtaggacaa ccattagagg gaattctggc aatttggcgt 780
aatttatggg aagattcccg cgatctagct agtcacgcct tagcatatac tcgtgtccag 840
ttaaaatctg ctcaagaagc cctaaaacaa gccgagcgca gtcgcttacc gtgataa 897
<210> 98
<211> 297
<212> PRT
<213> 人工序列
<220>
<223> 变体277289
<400> 98
Met Asn Lys Leu Gly Val His Ala Leu Val Trp Glu Ala Gly Trp Ser
1 5 10 15
Arg Asp Glu Cys Ala Arg Ala Ile Ala Arg Thr Ala Glu Thr Gly Phe
20 25 30
Asp Phe Ile Glu Val Pro Ala Leu Asp Pro Ala Ser Ile Asp Ala Glu
35 40 45
Phe Thr Arg Arg Glu Leu Glu Arg His Gly Leu Gly Val Thr Phe Ser
50 55 60
Leu Gly Leu Asp Ala Gln Thr Asp Ile Ser Ser Gly Asp Pro Glu Arg
65 70 75 80
Ala Ala Arg Gly Lys Ala Lys Leu Asp Asp Val Leu Arg Val Ala Arg
85 90 95
Asp Cys Gly Ala Thr His Val Cys Gly Ile Leu Tyr Ser Ala Phe Gln
100 105 110
Lys Asn Ala Val Pro Thr Thr Arg Ala Gly Val Ala Met Ala Ala Asp
115 120 125
Ile Leu Gly Gln Val Ala Asp Thr Ala Ala Gln Tyr Gly Ile Thr Leu
130 135 140
Gly Leu Glu Val Val Asn Arg Tyr Glu Thr Asn Val Leu Asn Thr Ala
145 150 155 160
Ser Gln Gly Val Glu Leu Ile Glu Arg Ile Gly Arg Pro Asn Val Lys
165 170 175
Val His Leu Asp Thr Tyr His Met Asn Ile Glu Glu Ser Asp Ile Met
180 185 190
Ser Ala Ile Arg Asp Thr Gly Asp Arg Leu Gly Tyr Phe His Ile Gly
195 200 205
Asp Ser His Arg Gly Tyr Leu Gly Ser Gly Asn Val Asp Phe Thr Ala
210 215 220
Val Phe Arg Ala Leu Val Phe Ser Gly Tyr Thr Gly Pro Ile Thr Phe
225 230 235 240
Glu Ser Phe Ser Ser Arg Val Val Gly Gln Pro Leu Glu Gly Ile Leu
245 250 255
Ala Ile Trp Arg Asn Leu Trp Glu Asp Ser Arg Asp Leu Ala Ser His
260 265 270
Ala Leu Ala Tyr Thr Arg Val Gln Leu Lys Ser Ala Gln Glu Ala Leu
275 280 285
Lys Gln Ala Glu Arg Ser Arg Leu Pro
290 295
<210> 99
<211> 897
<212> DNA
<213> 人工序列
<220>
<223> 变体277290的编码序列
<400> 99
atgaataagt taggtgtgca cgcattagtt tgggaagcgg gttggagtcg tgatgagtgt 60
gctcgtgcca tcgcacgcac cgcggaaacg ggatttgact tcattgaagt cccagcgtta 120
gatccggcaa gcattgatgc agagtttact cgcagagagt tagaacgcca tgggttggga 180
gtaacctttt cgcttggact cgatgcgcaa acagacatta gttctggtga tccggaacgc 240
gcagcgcggg gtaaagctaa attaaaagat gtcttacgtg tagcccggga ttgtggagcg 300
actcatgtct gtggaattct ctatagtgca tttcaaaaaa atgcagttcc tacgacccgt 360
gcgggtgtcg ccatggccgc ggacatttta ggacaggtag ctgatactgc agcacaatac 420
ggtattactt tggggttaga agtcgttaac cgttatgagt caaatgtatt gaacaccgcg 480
tcacagggtg ttgaacttat tgagcgtatt ggtcgtccca acgtaaaagt gcatttagat 540
acgtatcaca tgaatattga agagagcgat attatgagcg cgatcagaga tacgggagac 600
aggctagggt atttccatat tggcgattct catcgtggtt acctgggttc cggaaacgtc 660
gactttactg ccgtatttag ggcgctggta ttttctggat atacgggacc gattacattt 720
gagtcattct ccagtagagt cgtaggacaa ccattagagg gaattctggc aatttggcgt 780
aatttatggg aagattcccg cgatctagct agtcacgcct tagcatatac tcgtgtccag 840
ttaaaatctg ctcaagaagc cctaaaacaa gccgagcgca gtcgcttacc gtgataa 897
<210> 100
<211> 297
<212> PRT
<213> 人工序列
<220>
<223> 变体277290
<400> 100
Met Asn Lys Leu Gly Val His Ala Leu Val Trp Glu Ala Gly Trp Ser
1 5 10 15
Arg Asp Glu Cys Ala Arg Ala Ile Ala Arg Thr Ala Glu Thr Gly Phe
20 25 30
Asp Phe Ile Glu Val Pro Ala Leu Asp Pro Ala Ser Ile Asp Ala Glu
35 40 45
Phe Thr Arg Arg Glu Leu Glu Arg His Gly Leu Gly Val Thr Phe Ser
50 55 60
Leu Gly Leu Asp Ala Gln Thr Asp Ile Ser Ser Gly Asp Pro Glu Arg
65 70 75 80
Ala Ala Arg Gly Lys Ala Lys Leu Lys Asp Val Leu Arg Val Ala Arg
85 90 95
Asp Cys Gly Ala Thr His Val Cys Gly Ile Leu Tyr Ser Ala Phe Gln
100 105 110
Lys Asn Ala Val Pro Thr Thr Arg Ala Gly Val Ala Met Ala Ala Asp
115 120 125
Ile Leu Gly Gln Val Ala Asp Thr Ala Ala Gln Tyr Gly Ile Thr Leu
130 135 140
Gly Leu Glu Val Val Asn Arg Tyr Glu Ser Asn Val Leu Asn Thr Ala
145 150 155 160
Ser Gln Gly Val Glu Leu Ile Glu Arg Ile Gly Arg Pro Asn Val Lys
165 170 175
Val His Leu Asp Thr Tyr His Met Asn Ile Glu Glu Ser Asp Ile Met
180 185 190
Ser Ala Ile Arg Asp Thr Gly Asp Arg Leu Gly Tyr Phe His Ile Gly
195 200 205
Asp Ser His Arg Gly Tyr Leu Gly Ser Gly Asn Val Asp Phe Thr Ala
210 215 220
Val Phe Arg Ala Leu Val Phe Ser Gly Tyr Thr Gly Pro Ile Thr Phe
225 230 235 240
Glu Ser Phe Ser Ser Arg Val Val Gly Gln Pro Leu Glu Gly Ile Leu
245 250 255
Ala Ile Trp Arg Asn Leu Trp Glu Asp Ser Arg Asp Leu Ala Ser His
260 265 270
Ala Leu Ala Tyr Thr Arg Val Gln Leu Lys Ser Ala Gln Glu Ala Leu
275 280 285
Lys Gln Ala Glu Arg Ser Arg Leu Pro
290 295

Claims (8)

1.一种编码蛋白质的核酸，其中所述蛋白质的氨基酸序列选自由SEQ ID NO:16、18、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和100组成的组。
2.一种微生物，所述微生物包含如权利要求1所述的核酸。
3.如权利要求2所述的微生物，其中所述微生物选自由地衣芽孢杆菌、酿酒酵母、粟酒裂殖酵母、恶臭假单胞菌、毕赤酵母属物种、曲霉属物种、里氏木霉、谷氨酸棒状杆菌、大肠杆菌和枯草芽孢杆菌组成的组。
4.一种蛋白质，所述蛋白质包含选自由SEQ ID NO:16、18、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和100组成的组的氨基酸序列。
5.一种固体基质，所述固体基质包含如权利要求4所述的蛋白质。
6.一种柱，所述柱包含如权利要求5所述的固体基质，并且被配置以在所述固体基质上接收包含果糖的输入溶液并且允许包含阿洛酮糖的输出溶液的排出。
7.一种产生蛋白质的方法，所述蛋白质包含选自由SEQ ID NO:16、18、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和100组成的组的氨基酸序列，所述方法包括：
(a)培养如权利要求2所述的微生物；以及
(b)回收所述蛋白质。
8.一种生产阿洛酮糖的方法，所述方法包括在适合于将至少一部分果糖转换为阿洛酮糖的条件下，使包含果糖的溶液与如权利要求4所述的蛋白质接触一段时间。
CN201980056241.9A 2018-08-08 2019-08-07 差向异构酶及其用途 Pending CN112639092A (zh)

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KR20210044241A (ko) 2021-04-22
EP3833756C0 (en) 2023-06-07
EP3833756B1 (en) 2023-06-07
AU2019319816A1 (en) 2021-03-25
US20220145344A1 (en) 2022-05-12
US11859228B2 (en) 2024-01-02

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