CN108588043B - 一种单加氧酶复合体及其在手性亚砜合成中的应用 - Google Patents
一种单加氧酶复合体及其在手性亚砜合成中的应用 Download PDFInfo
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Abstract
本发明涉及分子生物学领域的一种单加氧酶复合体，所述的单加氧酶蛋白复合体由四个亚基组成，其氨基酸残基序列如SEQ ID No.1所示。利用所述的单加氧酶复合体能制备高光学纯度的(R)构型亚砜。相对于其它现有的制备方法，使用所述制备方法反应时间短，反应条件温和，对环境友好，操作简便。
Description
技术领域
本发明涉及分子生物学领域，具体涉及一种单加氧酶复合体及其在手性亚砜合成中的应用。
背景技术
手性亚砜是一类非常重要的化合物，可作为手性中间体和辅剂、手性配体、催化剂以及临床药物，在有机合成和药物合成中有广泛的应用。现有的手性亚砜合成技术还存在着过度氧化、副产物多、反应条件苛刻等不足。生物酶的高效和高选择性，使得生物催化技术可望发展成为工业化绿色制备手性亚砜类药物的新途径。但现有研究表明，高活性和高对映选择性的手性亚砜合成酶还十分匮乏，无法满足绿色工业化生产的需求，获得高催化效率的生物酶和相应的生物催化合成方法，仍然是手性亚砜生物催化制备发展过程中的难点和瓶颈。
发明内容
本发明旨在克服上述缺点，提供一种高催化活性的单加氧酶复合体，以及该单加氧酶复合体在手性亚砜生物催化合成中的应用。
为了达到上述目的，本发明提供如下基础技术方案：单加氧酶复合体pmTod，包含4个亚基，命名为：pmTodA，pmTodB，pmTodC，pmTodD；四个所述亚基的氨基酸残基序列分别如SEQ ID No.1、SEQ ID No.2、SEQ ID No.3和SEQ ID No.4所示。
pmTod是该单加氧酶复合体的英文解释。
本发明所涉及的单加氧酶复合体(pmTod)是从实验室保存的菌种中分离获得，获得的方法为本领域常规方法；较佳地为从重组表达pmTod的基因工程菌中分离获得或者人工合成获得。
以下是对基础技术方案的优化：
优化方案一：所述单加氧酶复合体为具有催化硫醚底物生成(R)-亚砜的蛋白质。
优化方案二：包含上述基础方案或者优化方案一的单加氧酶复合体的蛋白质编码基因。
优化方案三，基于优化方案二：所述蛋白质编码基因的核苷酸序列如SEQ IDNo.5、SEQ ID No.6、SEQ ID No.7和SEQ ID No.8所示。
本发明所述的单加氧酶复合体pmTod基因是从本实验室保存的菌种中克隆获得，获得的方法为本领域常规；较佳地为提取菌株基因组DNA，通过PCR扩增获得，或者根据SEQID No.5、SEQ ID No.6、SEQ ID No.7和SEQ ID No.8所示核苷酸序列人工合成获得。
优化方案四，包含优化方案二的蛋白质编码基因的重组表达载体。
优化方案五，包含优化方案三的蛋白质编码基因的重组表达载体。
本发明所述重组表达载体由通过本领域常规方法将所述pmTod基因连接于各种骨架载体上构建而成；较佳地，可通过下述方法制得：将通过PCR所得的pmTodA(SEQ ID No.1)和pmTodB(SEQ ID No.2)基因和骨架载体pET-Dute-1连接形成重组载体pETDute1-pmTodA-B，将通过PCR所得的pmTodC(SEQ ID No.3)和pmTodD(SEQ ID No.4)基因和骨架载体pRSF-Dute-1连接形成重组载体pRSFDute1-pmTodC-D。
优化方案六，包含优化方案四或优化方案五中所述重组载体的基因工程菌。
本发明所述基因工程菌由通过本领域常规方法将所述重组表达载体转化至宿主微生物中制得；所述宿主微生物可为本领域常规的各种宿主微生物，只要能满足所述重组表达载体可稳定地自行复制，且所携带的亚砜还原酶基因可被有效表达即可；较佳地，可通过下述方法制得：将重组载体pETDute1-pmTodA-B与pRSFDute1-pmTodC-D转化至大肠杆菌BL21(DE3)中。
本发明还提供了基础方案所述的单加氧酶复合体在手性亚砜制备中的应用，表达如权利要求1所述单加氧酶复合体，将其悬浮于反应缓冲液中，加入硫醚底物，放入摇床反应后，再加入乙酸乙酯萃取并收集有机相，通过柱层析分离获得(R)构型的手性亚砜。
优化方案七，基于上述单加氧酶复合体在手性亚砜制备中的应用，其特征在于：所述缓冲液为50mM浓度、pH 6～9的磷酸钠缓冲液；所述的摇床转速为200-250rpm/min；反应温度为25～35℃；反应时间为12～24小时；所述的硫醚底物浓度为2～8mM。
优化方案八，所述单加氧酶复合体可以为纯化后的重组酶蛋白，含重组酶蛋白的粗酶液和含重组酶蛋白的基因工程菌休止细胞、基因工程菌生长期细胞、基因工程菌固定化细胞中的一种。
本发明的积极进步效果在于：利用所述的单加氧酶复合体能制备高光学纯度的(R)构型亚砜。相对于其它现有的制备方法，使用所述制备方法反应速率高，耗时短；所述制备方法可在常温、常压及水相环境中进行，反应条件温和，且所述制备方法不需使用强氧化剂或有毒试剂，因此具有较高的催化活性，对环境友好，操作简便。
含重组单加氧酶复合体的基因工程菌催化消旋体亚砜底物制备手性亚砜的反应过程为：
附图说明
图1为本发明的单加氧酶复合体重组表达质粒的示意图；
图2为pmTod重组蛋白SDS-PAGE凝胶电泳图片；泳道1为蛋白质分子量标志；泳道2为pmTod重组蛋白的表达情况，箭头所示为pmTod复合体的4个亚基条带。
具体实施方式
下面通过实施例的方式进一步说明本发明，但并不因此将本发明限制在所述实施例范围之中。下列实施例中未注明具体条件的实验方法，按照常规方法和条件，或按照商品说明书选择。
实施例1：单加氧酶复合体基因的获得，包括以下步骤：
以基因组DNA为模板，使用引物1：5’-GGCCAGATCTCATGAATCAGACCGACACATC-3’和2：5’-AATTCTCGAGGCGTGTCGCCTTCAGCGCG-3’进行PCR扩增获得pmTodA基因；使用引物3：5’-GGAAGGATCCGATGATTGATTCAGCCAACAG-3’和4：5’-AACCGTCGACCTAGAAGAAGAAACTGAGG-3’进行PCR扩增获得pmTodB基因；使用引物5：5’-GGCCAGATCTATGGCGTTGCCCGGCAGCC-3’和6：5’-AATTCTCGAG ACGTTAGGTCTCCTTCATTCG-3’进行PCR扩增获得pmTodC基因；使用引物7：5’-GGAAGGATCCATGACTTGGACATACATATT-3’和8：5’-AACCGTCGACCTTCAACTCCCCGTTGTCG-3’进行PCR扩增获得pmTodD基因。PCR反应体系如下：2×Taq PCR Master Mix 10.0μL、基因组DNA1μL、上下游引物各0.5μL、ddH2O 8.0μL。PCR反应条件：95℃10min；98℃10s，58℃30s，72℃30s，30个循环循环；72℃延伸5min。PCR产物以1％琼脂糖凝胶电泳验证是否获得符合目的基因大小的片段。
实施例2：单加氧酶复合体基因工程菌的构建，包括以下步骤：
用限制性内切酶BamH I和Sal I对含有pmTodA基因序列的DNA片段及载体pETDute-1进行双酶切，酶切回收的目的片段和载体。用T4 DNA连接酶，16℃连接4h后，连接产物转化大肠杆菌DH5α。过夜培养后，挑取长出的单克隆菌落摇菌并提取质粒，利用BamH I和Sal I对重组质粒pETDute1-pmTodA进行双酶切检测。接着，接着用Bgl II和Xho I对pmTodB基因及重组质粒pETDute1-pmTodA进行同样的操作后，获得重组载体pETDute1-pmTodA-B。接着，用限制性内切酶BamH I和Sal I对含有pmTodC基因序列的DNA片段及载体pRSFDute-1进行双酶切，用T4 DNA连接酶连接后，连接产物转化大肠杆菌DH5α，获得重组质粒pRSFDute1-pmTodC进行双酶切检测。接着，接着用Bgl II和Xho I对pmTodD基因及重组质粒pRSFDute1-pmTodC进行同样的操作后，获得重组载体pRSFDute1-pmTodC-D。最后，将两个重组载体pETDute1-pmTodA-B和pRSFDute1-pmTodC-D共转化到大肠杆菌菌株BL21(DE3)中，获得含pmTod重组表达质粒的基因工程菌，保存于-80℃冰箱。
实施例3：单加氧酶复合体重组蛋白的获得，包括以下步骤：
将保存于甘油中含重组质粒的基因工程菌BL21(DE3)划平板活化后，挑单菌落于2ml含相应抗生素的液体LB培养基中，37℃振荡培养12h，次日以2％接种量转接于新鲜的含抗生素的100mL LB液体培养基中，37℃250rpm振荡培养OD600为0.6(约3h)，加入终浓度为0.2mM的IPTG，25℃160rpm诱导培养8h。诱导结束后5000rpm/min离心5min收集菌体，菌体重悬于PBS缓冲液中，超声波破碎菌体，15000rpm离心5min去细胞碎片，取上清与2x上样缓冲液混合后，于恒温金属浴中100℃加热5min后作SDS-PAGE电泳分析。附图2的结果说明，获得了大量的可溶性表达的亚砜还原酶。
实施例4：利用含重组亚砜还原酶的基因工程菌制备(R)构型手性苯甲亚砜，包括以下步骤：
1)基因工程菌的培养：挑取构建好的基因工程菌单菌落于2mL LB培养基，于37℃摇床180rpm的转速下培养12h后，转入含有50mL LB培养基的250mL的大摇瓶，培养至OD600＝0.6时加入终浓度为0.2μM的IPTG，继续培养14h后，于5000rpm的条件下离心去除上清液，获得菌株的湿细胞备用；
2)生物转化：将所培养菌株的湿细胞，以30g/L的细胞浓度悬浮于5mL、pH为7.5的PBS缓冲液中，将底物苯甲硫醚2.5mg加入上述5mL反应体系中，放入摇床于30℃，250rpm条件下反应16h后，加入乙酸乙酯萃取，收集15瓶萃取后的有机相，用无水硫酸钠干燥，离心去除硫酸钠并过滤。加压蒸去溶剂，柱层析分离，获得(R)-苯甲亚砜。产物做手性HPLC分析，(R)-苯甲亚砜28％产率，99％ee。
以上所述，仅是本发明的较佳实施例而已，并非对本发明作任何形式上的限制，任何未脱离本发明技术方案内容，依据本发明的技术实质对以上实施例所作的任何简单修改、等同变化与修饰，均仍属于本发明技术方案的范围内。
<110> 遵义医学院
<120> 一种单加氧酶复合体及其在手性亚砜合成中的应用
<130> 2018
<160> 1
<170> PatentIn version 3.5
<210> 1
<211> 455
<212> PRT
<213> 人工序列
<400> 1
Met Asn Gln Thr Asp Thr Ser Pro Ile Arg Leu Arg Arg Ser Trp Asn
1 5 10 15
Thr Ser Glu Ile Glu Ala Leu Phe Asp Glu His Ala Pro Cys Ile Asp
20 25 30
Pro Arg Ile Tyr Thr Asp Glu Asp Leu Tyr Gln Leu Glu Leu Glu Arg
35 40 45
Val Phe Ala Arg Ser Trp Leu Leu Leu Gly His Glu Thr Pro Arg Arg
50 55 60
Lys Pro Gly Asp Tyr Ile Thr Thr Tyr Met Gly Glu Asp Pro Val Val
65 70 75 80
Val Val Arg Gln Lys Asp Ala Ser Ile Ala Val Phe Leu Asn Gln Cys
85 90 95
Arg His Arg Gly Met Arg Ile Cys Arg Ala Asp Ala Gly Asn Ala Lys
100 105 110
Ala Phe Thr Cys Ser Tyr His Gly Trp Ala Tyr Asp Thr Ala Gly Asn
115 120 125
Leu Val Asn Val Pro Tyr Ser Gly Glu Ser Phe Ala Cys Leu Asn Lys
130 135 140
Lys Glu Trp Ser Pro Leu Lys Ala Arg Val Glu Thr Tyr Lys Gly Leu
145 150 155 160
Ile Phe Ala Asn Trp Asp Glu Asn Ala Val Asp Leu Asp Thr Tyr Leu
165 170 175
Gly Glu Ala Lys Phe Tyr Met Asp His Met Leu Asp Arg Thr Glu Ala
180 185 190
Gly Thr Glu Ala Ile Pro Gly Val Gln Lys Trp Val Ile Pro Cys Asn
195 200 205
Trp Lys Phe Ala Ala Glu Gln Phe Cys Ser Asp Met Tyr His Ala Gly
210 215 220
Thr Thr Ser His Leu Ser Gly Ile Leu Ala Gly Leu Pro Glu Asp Leu
225 230 235 240
Glu Met Ala Asp Leu Ala Pro Pro Thr Val Gly Lys Gln Tyr Arg Ala
245 250 255
Ser Trp Gly Gly His Gly Ser Gly Phe Tyr Val Gly Asp Pro Asn Leu
260 265 270
Met Leu Ala Glu Met Gly Pro Lys Val Thr Ser Tyr Trp Thr Glu Gly
275 280 285
Pro Ala Ser Glu Lys Ala Ala Glu Arg Leu Gly Ser Val Glu Arg Gly
290 295 300
Ser Lys Leu Met Asp Asp His Met Thr Val Phe Pro Thr Cys Ser Phe
305 310 315 320
Leu Pro Gly Ile Asn Thr Val Arg Thr Trp His Pro Arg Gly Pro Asn
325 330 335
Glu Val Glu Val Trp Ala Phe Thr Val Val Asp Ala Asp Ala Pro Asp
340 345 350
Asp Ile Lys Glu Glu Phe Arg Arg Cys Ala Leu Arg Thr Phe Ser Ala
355 360 365
Gly Gly Gly Gly Glu Gln Asp Asp Gly Glu Asn Trp Val Glu Ile Gln
370 375 380
His Ile Leu Arg Gly His Lys Ala Arg Ser Arg Pro Phe Asn Ala Glu
385 390 400 405
Met Ser Met Asp Gln Thr Val Asp Asn Asp Pro Val Tyr Pro Gly Arg
410 415 420
Ile Ser Asn Asn Val Tyr Ser Glu Glu Ala Ala Arg Gly Leu Tyr Ala
425 430 435
His Trp Leu Arg Met Met Thr Ser Pro Asp Trp Asp Ala Leu Lys Ala
440 445 450
Thr Arg
455
<210> 2
<211> 187
<212> PRT
<213> 人工序列
<400> 2
Met Ile Asp Phe Ala Asn Arg Ala Asp Val Phe Leu Arg Lys Pro Ala
1 5 10 15
Pro Val Ala Pro Glu Leu Gln His Glu Val Glu Gln Phe Tyr Tyr Trp
20 25 30
Glu Ala Lys Leu Leu Asn Asp Arg Arg Phe Glu Glu Trp Phe Ala Leu
35 40 45
Ile Ala Glu Asp Ile His Tyr Phe Met Pro Ile Arg Thr Thr Arg Ile
50 55 60
Met Arg Asp Ser Arg Leu Glu Tyr Ser Gly Ser Arg Glu Tyr Ala His
65 70 75 80
Phe Asp Asp Asp Ala Thr Met Met Lys Gly Arg Leu Arg Lys Ile Thr
85 90 95
Ser Asp Val Ser Trp Ser Glu Asn Pro Ala Ser Arg Thr Arg His Leu
100 105 110
Val Ser Asn Val Met Ile Val Gly Ala Glu Ala Glu Gly Glu Tyr Glu
115 120 125
Ile Ser Ser Ala Phe Ile Val Tyr Arg Asn Arg Leu Glu Arg Gln Leu
130 135 140
Asp Ile Phe Ala Gly Glu Arg Arg Asp Thr Leu Arg Arg Ile Leu Ser
145 150 155 160
Glu Ala Gly Phe Glu Ile Val Asn Arg Thr Ile Leu Ile Asp Ser Cys
165 170 175
Thr Ile Leu Ala Asn Asn Leu Ser Phe Phe Phe
180 185
<210> 3
<211> 295
<212> PRT
<213> 人工序列
<400> 3
Met Ala Leu Pro Gly Ser Gln Leu Pro Gly Val Val Leu Ser Arg Thr
1 5 10 15
Tyr Gly Asp Val Gln Val Leu Arg Asp Ser Trp Thr Ser Ala Thr Arg
20 25 30
Leu Leu Ile Val Gly Gly Gly Leu Ile Gly Cys Glu Val Ala Thr Thr
35 40 45
Ala Arg Lys Leu Gly Leu Ser Asp Val Thr Ala Glu Ala Gly Asp Glu
50 55 60
Leu Leu Val Arg Val Leu Gly Arg Arg Ser Met Ala Trp Leu Arg Gly
65 70 75 80
Leu Leu Thr Glu Leu Gly Val Gln Val Glu Leu Gly Thr Gly Val Val
85 90 95
Gly Phe Ser Gly Glu Gly Gln Leu Glu Gln Val Met Ala Ser Asp Gly
100 105 110
Arg Ser Phe Val Ala Asp Ser Ala Leu Ile Cys Val Gly Ala Glu Pro
115 120 125
Ala Asp Gln Leu Ala Arg Gln Ala Gly Leu Ala Cys Asp Arg Gly Val
130 135 140
Ile Val Asp His Cys Gly Ala Thr Leu Ala Lys Gly Val Phe Ala Val
145 150 155 160
Gly Asp Val Ala Ser Trp Pro Leu Arg Ala Gly Gly Arg Arg Ser Leu
165 170 175
Glu Thr Tyr Met Asn Ala Gln Arg Gln Ala Ala Ala Val Ala Ala Ala
180 185 190
Ile Leu Gly Lys Asn Val Ser Ala Pro Gln Leu Pro Val Ser Trp Thr
195 200 205
Glu Ile Ala Gly His Arg Met Gln Met Ala Gly Asp Ile Glu Gly Pro
210 215 220
Gly Asp Phe Val Ser Arg Gly Met Pro Gly Ser Gly Ala Ala Arg Ala
225 230 235 240
Gly Arg Leu Arg Arg Ile Gln Ala Val Val Ala Val Asp Ala Pro Arg
245 250 255
Asp Phe Ala Leu Ala Thr Arg Leu Val Glu Ala Arg Ala Ala Ile Glu
260 265 270
Pro Ala Arg Leu Ala Asp Leu Ser Asn Ser Met Arg Asp Phe Val Arg
275 280 285
Ala Asn Glu Gly Asp Leu Thr
290 295
<210> 4
<211> 107
<212> PRT
<213> 人工序列
<400>4
Met Thr Trp Thr Tyr Ile Leu Arg Gln Gly Asp Leu Pro Pro Gly Glu
1 5 10 15
Met Gln His Val Glu Gly Gly Pro Glu Pro Val Met Val Cys Asn Val
20 25 30
Asp Val Leu Phe Phe Ala Val Gln Asp Thr Cys Thr His Gly Asp Trp
35 40 45
Ala Leu Ser Asp Gly Tyr Leu Asp Gly Thr Val Val Glu Cys Thr Leu
50 55 60
His Phe Gly Lys Phe Cys Val Arg Thr Gly Lys Val Lys Ala Leu Pro
65 70 75 80
Ala Cys Lys Pro Ile Lys Val Phe Pro Ile Ala Val Glu Gly Asp Glu
85 90 95
Val His Val Ile Phe Asp Asn Gly Glu Leu Lys
100 105
SEQUENCE LISTING
<110> 遵义医学院
<120> 一种单加氧酶复合体及其在手性亚砜合成中的应用
<130> 2017
<160> 4
<170> PatentIn version 3.3
<210> 1
<211> 1353
<212> DNA
<213> 人工序列
<400> 5
atgaatcaga ccgacacatc acctatcagg ctgcgcagga gctggaacac cagcgagata 60
gaagcgctct ttgacgagca tgcaccatgt atcgatccgc gcatttatac cgatgaggat 120
ctgtaccaac tcgaactgga gcgtgtcttc gcccggtcct ggctgctgtt ggggcatgaa 180
accccccgtc gcaagccggg cgattacatc acgacctaca tgggtgaaga ccctgtcgtg 240
gtcgtccggc agaaagacgc cagcattgcc gtgttcctga accagtgccg ccaccgtggc 300
atgcgcatct gccgcgcgga tgccggaaac gcgaaggcgt tcacttgcag ctaccacggg 360
tgggcttacg acaccgccgg caatcttgtc aatgtgcctt actctggcga atccttcgcg 420
tgcctgaaca agaaggaatg gagcccgctg aaggcccggg tagaaaccta caagggcctg 480
attttcgcca actgggatga gaacgctgta gacctcgaca cgtatctggg cgaggcgaag 540
ttctacatgg accacatgct cgaccgcacc gaggccggca ccgaagcgat cccgggcgtg 600
cagaagtggg tcattccctg taactggaaa ttcgccgcag agcagttttg cagcgacatg 660
taccatgccg ggacgacctc gcatctgtct ggcatcctgg caggcctgcc agaagacctt 720
gaaatggccg accttgctcc gccgacagtt ggcaagcagt accgtgcgtc atggggcgga 780
catggaagtg gcttctatgt cggcgacccc aatctgatgc ttgcggaaat ggggccaaag 840
gtcaccagct actggaccga aggccccgcg tcggaaaagg cggccgaacg tctgggtagc 900
gtggagcgcg gctcgaaact catggatgat cacatgaccg tcttccccac gtgttccttc 960
ctcccaggta tcaatacggt ccggacatgg catccgcgcg ggccgaacga ggtcgaggta 1020
tgggcgttta cggtggtcga tgctgatgct cctgacgata tcaaggaaga gttccggcga 1080
tgtgcgctgc gcaccttctc tgccggtggc ggcggagagc aggacgacgg ggagaactgg 1140
gtcgagatcc agcacatcct gcgaggccac aaggcgcgga gccgcccttt caatgccgag 1200
atgagcatgg accagaccgt cgacaacgac ccggtttacc ccgggcggat cagcaacaac 1260
gtctacagcg aggaagctgc ccgcgggctc tatgcccatt ggctgcggat gatgacatcc 1320
cccgactggg acgcgctgaa ggcgacacgc tga 1353
<210> 2
<211> 564
<212> DNA
<213> 人工序列
<400> 6
atgattgatt tcgccaacag agccgacgtc tttctccgca agccggcacc cgtagcgccc 60
gaactgcagc acgaagtcga gcagttctac tattgggagg ccaagcttct caacgatcgc 120
cgcttcgagg agtggttcgc gctgattgcg gaagacattc actacttcat gcccattcgc 180
accacgcgga tcatgcggga ctcgcgcctt gaatactcag gctcccgaga gtacgcgcac 240
ttcgatgacg acgccacgat gatgaaggga cgcttgcgca agatcacgtc cgacgtgagc 300
tggtccgaga accccgcatc gcggacccgg catctcgtga gcaacgtgat gatcgtcggc 360
gcagaggcag aaggggagta cgaaatctca agcgccttca ttgtgtaccg caatcgtctg 420
gagcggcagc tcgacatctt tgccggtgag cgtcgcgata cgttgcgccg tatcttgagc 480
gaggccgggt tcgagatcgt caatcggacc atcctgatcg actcttgcac catcctggcc 540
aataacctca gtttcttctt ctag 564
<210> 3
<211> 888
<212> DNA
<213> 人工序列
<400> 7
atggcgttgc ccggcagcca actgcccggc gtcgtattgt cgcgcaccta cggtgacgtg 60
caggtattgc gcgatagttg gacttccgcg acgcggctgc tgattgtggg tggcggattg 120
atcggctgcg aggtcgcgac gacggcgcgc aagctcggcc tgtcggatgt gaccgcggag 180
gcaggtgatg aactgctggt ccgagtactt gggcggcgca gtatggcctg gctgcgcggc 240
ctgctgacag aacttggtgt gcaggtcgag ttgggaacgg gtgtcgtagg tttttctggt 300
gagggccagc tcgaacaagt catggccagc gatgggcgca gcttcgtagc cgatagcgca 360
ctcatttgcg tcggcgcgga gcccgcggat caacttgcgc gtcaagcggg cttggcatgt 420
gaccgcggcg tcattgtcga tcactgcggt gcgacgcttg ccaaaggcgt attcgccgtc 480
ggagatgtgg ccagttggcc gctgcgcgcc ggcggccggc gttcgctcga aacctatatg 540
aacgcgcagc gccaagccgc cgcggtggct gcggccattc tggggaaaaa cgtatcggca 600
ccgcaactgc ccgtgtcctg gacggagatc gctgggcatc gcatgcagat ggcgggcgat 660
atcgaaggac ctggtgattt cgtctcgcgc ggcatgcccg gtagtggcgc tgcccgtgca 720
ggtcgcctgc gaaggattca ggcggtcgtc gcggtcgatg caccccgtga cttcgcgctt 780
gcaacccgat tggtagaagc ccgcgcggca atcgagccag cacggctggc agatctttca 840
aacagtatgc gcgattttgt tcgtgcgaat gaaggagacc taacgtga 888
<210> 4
<211> 324
<212> DNA
<213> 人工序列
<400> 8
atgacttgga catacatatt gcggcagggt gacctgccac ccggtgagat gcagcacgtc 60
gaaggcggcc cggaacctgt gatggtctgc aacgtcgatg ttctgttctt cgcggtgcag 120
gatacctgca cgcatgggga ctgggcgttg tcggatggtt acctggacgg aacggttgtc 180
gaatgcacgt tgcatttcgg caagttctgc gtgcggaccg ggaaggtgaa ggcgctgcct 240
gcttgcaaac ctatcaaggt attcccaatt gcagtcgaag gcgatgaagt gcacgtcata 300
ttcgacaacg gggagttgaa gtga 324
Claims (8)
1.一种单加氧酶复合体，其特征在于：所述的单加氧酶复合体由四个亚基组成，四个所述亚基的氨基酸残基序列如SEQ ID No.1、SEQ ID No.2、SEQ ID No.3和SEQ ID No.4所示。
2.一种编码如权利要求1所述单加氧酶复合体的基因。
3.如权利要求2所述的基因，其特征在于：所述基因的核苷酸序列如SEQ ID No.5、SEQID No.6、SEQ ID No.7和SEQ ID No.8所示。
4.一种包含如权利要求3所述基因的重组表达载体。
5.一种包含如权利要求4所述基因的重组表达载体。
6.一种包含如权利要求4或5所述的重组载体的基因工程菌。
7.如权利要求1所述的单加氧酶复合体在手性亚砜制备中的应用，其特征在于：表达如权利要求1所述单加氧酶复合体，将其悬浮于反应缓冲液中，加入硫醚底物，放入摇床反应后，再加入乙酸乙酯萃取并收集有机相，通过柱层析分离获得(R)构型的手性亚砜。
8.如权利要求7所述的单加氧酶复合体在手性亚砜制备中的应用，其特征在于：所述反应缓冲液为50mM浓度、pH 6～9的磷酸钠缓冲液；所述的摇床转速为200-250rpm/min；反应温度为25～35℃；反应时间为12～24小时；所述的硫醚底物浓度为2～8mM。
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