微生物环氧水解酶催化机制及应用研究进展

曹菲; 李永泉; 毛旭明

doi:10.12211/2096-8280.2020-004

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微生物环氧水解酶催化机制及应用研究进展

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- 微生物环氧水解酶催化机制及应用研究进展
- Recent development in catalytic mechanisms and applications of microbial epoxide hydrolases
- 合成生物学 2020年1卷第5期页码：528-539
- 作者机构：
  
  1.浙江大学药物生物技术研究所，浙江杭州 310058
  2.浙江省微生物生化与代谢工程重点实验室，浙江杭州 310058
- 作者简介：
  
  作者简介:曹菲（1995—），男，博士研究生，研究方向为微生物药物生物合成、微生物天然产物生物合成的酶学机制和化学机制研究、基于合成生物学的微生物药物开发。E-mail：feecao@zju.edu.cn
  [ "李永泉（1962—），男，博士，浙江大学求是特聘教授。研究方向为微生物合成生物学、微生物次级代谢调控和微生物制药。E-mail：lyq@zju.edu.cn" ]
  [ "毛旭明（1978—），男，博士，教授，研究方向为基于合成生物学的微生物药物开发、微生物药物生物合成的调控机制研究、基于多组学的新活性和新结构微生物天然产物挖掘、微生物天然产物生物合成的酶学机制和化学机制研究。E-mail：xmmao@zju.edu.cn" ]
- 基金信息：
  
  国家重点研发计划项目(2019YFA0905400)
- DOI：10.12211/2096-8280.2020-004
  中图分类号： Q 939.97
- 收稿：2020-02-27，
  
  修回：2020-08-07，
  
  纸质出版：2020-10-31
- 稿件说明：
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曹菲, 李永泉, 毛旭明. 微生物环氧水解酶催化机制及应用研究进展[J]. 合成生物学, 2020, 1(5): 528-539

CAO Fei, LI Yongquan, MAO Xuming. Recent development in catalytic mechanisms and applications of microbial epoxide hydrolases[J]. Synthetic Biology Journal, 2020, 1(5): 528-539
曹菲, 李永泉, 毛旭明. 微生物环氧水解酶催化机制及应用研究进展[J]. 合成生物学, 2020, 1(5): 528-539 DOI： 10.12211/2096-8280.2020-004.

CAO Fei, LI Yongquan, MAO Xuming. Recent development in catalytic mechanisms and applications of microbial epoxide hydrolases[J]. Synthetic Biology Journal, 2020, 1(5): 528-539 DOI： 10.12211/2096-8280.2020-004.

摘要

微生物来源的环氧水解酶（epoxide hydrolases，EHs，EC 3.3.2.3）能不对称水解外消旋环氧化物生成手性环氧化物和邻二醇，催化效率高且区域、立体选择性强，有利于合成高纯度的手性化合物。因此，微生物EHs成为了手性药物合成的一种非常重要的生物催化剂，也是一种强有力的生物合成元件。近10年来，随着基因组学、分子生物学、化学生物学、结构生物学等技术的快速发展，研究者又从多种微生物体内发现了多种具有潜在应用价值的EHs。与此同时，研究者也对微生物来源的EHs的酶学特性、生物大分子结构与催化机理进行了深入的研究。本文介绍了几种目前研究比较透彻的EHs催化机制，并综述了近10年来最新发现的微生物来源EHs，这些EHs具备潜在的应用价值。此外，本文总结了EHs的应用进展，重点介绍了EHs在合成生物学领域的应用。利用酶的定向进化等技术提高EHs催化性能和串联多个合成元件高效合成手性产物，是当前主要的研究趋势。

Abstract

Microbial epoxide hydrolases (EHs

EC 3.3.2.3) catalyze the enantioselective ring opening of racemic epoxides to the chiral epoxides and vicinal diols. EHs have high catalytic efficiency and chemical-

region-

and stereo-selectivity without cofactors

and are conducive to the synthesis of high-purity chiral compounds by biotransformation. Since they were discovered

EHs have become very important catalysts and powerful biosynthetic elements for the green synthesis of chiral drugs in industry. In the last 10 years

with the rapid development of genomics

molecular biology

chemical biology and structural biology

researchers have found a variety of EHs from various microorganisms with potential applications. At the same time

researchers have also paid a lot of attention to the enzymatic properties

protein structure and catalytic mechanism of microbial EHs. This review introduces the currently well-understood catalytic mechanism of microbial EHs

suc

h as ArEH from

Agrobacterium radiobacter

and limonene 1

2-EH from

Rhodococcus erythropolis

. Moreover

it summarizes 30+ microbial EHs with potential values

which were newly discovered in the last decade based on genome mining of microorganisms

along with the cognate biosynthetic pathways for natural product production. At least 15 crystal structures of new microbial EHs have been elucidated

helping people further understand the catalytic mechanisms at atomic levels and laying the foundation of their evolutions and applications. In addition

the applications of EHs in the field of pharmaceuticals and synthetic biology are also highlighted. Nowadays

researchers are mainly focusing on the improvement of catalytic activity

specificity and efficiency

as well as enantio-purity and yield of the products from microbial EHs with two main strategies: random or rational mutations of enzymes and strains

and artificial design of enzyme cascades within chassis cells. In the future

the synthesis of chiral drugs catalyzed by EHs will commence on the evolution of enzymatic activity

and assembly of multi-enzyme instead of single-enzyme in a cell factory for efficient biocatalysis.

关键词

Keywords

references

CHEN Yijun , CHEN Chen , WU Xuri . Dicarbonyl reduction by single enzyme for the preparation of chiral diols [J ] . Chemical Society Reviews , 2012 , 41 ( 5 ): 1742 - 1753 .

STEINREIBER A , FABER K . Microbial epoxide hydrolases for preparative biotransformations [J ] . Current Opinion in Biotechnology , 2001 , 12 ( 6 ): 552 - 558 .

ZOCHER F , ENZELBERGER M M , BORNSCHEUER U T , et al . Epoxide hydrolase activity of Streptomyces stra ins [J ] . Journal of Biotechnology , 2000 , 77 ( 2/3 ): 287 - 292 .

MORISSEAU C , HAMMOCK B D . Epoxide hydrolases: mechanisms, inhibitor designs, and biological roles [J ] . Annual Review of Pharmacology and Toxicology , 2005 , 45 : 311 - 333 .

MANOJ K , ARCHELAS A , BARATTI J , et al . Microbiological transformations. Part 45: A green chemistry preparative scale synthesis of enantiopure building blocks of Eliprodil: elaboration of a high substrate concentration epoxide hydrolase-catalyzed hydrolytic kinetic resolution process [J ] . Tetrahedron , 2001 , 57 ( 4 ): 695 - 701 .

ORRU R V , FABER K . Stereoselectivities of microbial epoxide hydrolases [J ] . Current Opinion in Biotechnology , 1999 , 3 ( 1 ): 16 - 21 .

NESTL B M , HAMMER S C , NEBEL B A , et al . New generation of biocatalysts for organic synthesis [J ] . Angewandte Chemie International Edition , 2014 , 53 ( 12 ): 3070 - 3095 .

潘海峰 . 新颖水解酶CESH的催化机制及其高效催化工艺研究 [D ] . 杭州 : 浙江大学 , 2011 .

PAN Haifeng . Study on the catalytic mechanism of a novel hydrolase CESH and its catalytic process with a high efficiency [D ] . Hangzhou : Zhejiang University , 2011 .

壮晓健 , 金火喜 , 胡忠策 , 等 . 微生物环氧化物水解酶的研究进展 [J ] . 生物技术 , 2010 , 20 ( 1 ): 91 - 94 .

ZHUANG Xiaojian , JIN Huoxi , HU Zhongce , et al . Research progress of microbial epoxide hydrolase [J ] . Chinese Journal of Biotechnology , 2010 , 20 ( 1 ): 91 - 94 .

CHOI Won Jae , CHOI Cha Yong . Production of chiral epoxides: epoxide hydrolase-catalyzed enantioselective hydrolysis [J ] . Biotechnology and Bioprocess Engineering , 2005 , 10 ( 3 ): 167 .

FLOOR R J , WIJMA H J , JEKEL P A , et al . X-ray crystallographic validation of structure predictions used in computational design for protein stabilization [J ] . Proteins , 2015 , 83 ( 5 ): 940 - 951 .

KONG Xudong , YUAN Shuguang , LI Lin , et al . Engineering of an epoxide hydrolase for efficient bioresolution of bulky pharmaco substrates [J ] . Proceedings of the National Academy of Sciences of The United States Of America , 2014 , 111 ( 44 ): 15717 - 15722 .

LI Guangyue , ZHANG Hui , SUN Zhoutong , et al . Multiparameter optimization in directed evolution: engineering thermostability, enantioselectivity, and activity of an epoxide hydrolase [J ] . ACS Catalysis , 2016 , 6 ( 6 ): 3679 - 3687 .

HU Die , TANG Cunduo , YANG Biao , et al . Expression of a novel epoxide hydrolase of Aspergillus usamii E001 in Escherichia coli and its performance in resolution of racemic styrene oxide [J ] . Journal of Industrial Microbiology & Biotechnology , 2015 , 42 ( 5 ): 671 - 680 .

PARK Hongjae , MIN Byoungnam , JANG Yeongseon , et al . Comprehensive genomic and transcriptomic analysis of polycyclic aromatic hydrocarbon degradation by a mycoremediation fungus, Dentipellis sp. KUC8613 [J ] . Applied Microbiology and Biotechnology , 2019 , 103 ( 19 ): 8145 - 8155 .

JIN Huoxi , LI Yan , ZHANG Qianwei , et al . Enantioselective hydrolysis of styrene oxide and benzyl glycidyl ether by a variant of epoxide hydrolase from Agromyces mediolanus [J ] . Marine Drugs , 2019 , 17 ( 6 ): 367 .

DUARAH A , GOSWAMI A , BORA T C , et al . Enantioconvergent biohydrolysis of racemic styrene oxide to R -phenyl-1,2-ethanediol by a newly isolated filamentous fungus Aspergillus tubingensis TF1 [J ] . Applied Biochemistry and Biotechnology , 2013 , 170 ( 8 ): 1965 - 1973 .

CHEN Lin , SHEN ChenHonglei , WEI Chun , et al . Bioresolution of ( R )-glycidyl azide by Aspergillus niger ZJUTZQ208: a new and concise synthon for chiral vicinal amino alcohols [J ] . Applied Microbiology and Biotechnology , 2013 , 97 ( 6 ): 2609 - 2616 .

WOO Jung-Hee , KANG Ji-Hyun , HWANG Young-Ok , et al . Biocatalytic resolution of glycidyl phenyl ether using a novel epoxide hydrolase from a marine bacterium, Rhodobacterales bacterium HTCC2654 [J ] . Journal of Bioscience and Bioengineering , 2010 , 110 ( 4 ): 509 - 509 .

MIN Ji Young , LEE Eun Yeol . Biosynthesis of ( R )-1,2-phenylethanediol and ( R )-4-chloro-1,2-phenylethanediol by using two recombinant cells expressing enantiocomplementary epoxide hydrolases [J ] . Journal of Industrial and Engineering Chemistry , 2012 , 18 ( 1 ): 160 - 164 .

HORSMAN G P , LECHNER A , OHNISHI Y , et al . Predictive model for epoxide hydrolase-generated stereochemistry in the biosynthesis of nine-membered enediyne antitumor antibiotics [J ] . Biochemistry , 2013 , 52 ( 31 ): 5217 - 5224 .

ZHAO Jing , CHU Yanyan , LI Aitao , et al . An unusual ( R )-selective epoxide hydrolase with high activity for facile preparation of enantiopure glycidyl ethers [J ] . Advanced Synthesis & Catalysis , 2011 , 353 ( 9 ): 1510 - 1518 .

KUMAR R , WANI S I , CHAUHAN N S , et al . Cloning and characterization of an epoxide hydrolase from Cupriavidus metallidurans -CH34 [J ] . Protein Expression and Purification , 2011 , 79 ( 1 ): 49 - 59 .

XUE Feng , LIU Zhiqiang , ZOU Shuping , et al . A novel enantioselective epoxide hydrolase from Agromyces mediolanus ZJB120203: cloning, characterization and application [J ] . Process Biochemistry , 2014 , 49 ( 3 ): 409 - 417 .

WU Kai , WANG Hualei , SUN Huihui , et al . Efficient kinetic resolution of phenyl glycidyl ether by a novel epoxide hydrolase from Tsukamurella paurometabola [J ] . Applied Microbiology and Biotechnology , 2015 , 99 ( 22 ): 9511 - 9521 .

WEI Chun , LING Jinlong , SHEN Honglei , et al . Bioresolution production of (2 R , 3 S )-ethyl-3-phenylglycidate for chemoenzymatic synthesis of the taxol C-13 side chain by Galactomyces geotrichum ZJUTZQ200, a new epoxide-hydrolase-producing strain [J ] . Molecules , 2014 , 19 ( 6 ): 8067 - 8079 .

BELOTI L L , COSTA B Z , TOLEDO M A , et al . A novel and enantioselective epoxide hydrolase from Aspergillus brasiliensis CCT 1435: purification and characterization [J ] . Protein Expression and Purification , 2013 , 91 ( 2 ): 175 - 183 .

MADACKI J , LAVAL F , GRZEGORZEWICZ A , et al . Impact of the epoxide hydrolase EphD on the metabolism of mycolic acids in mycobacteria [J ] . The Journal of Biological Chemistry , 2018 , 293 ( 14 ): 5172 - 5184 .

HOTTA K , CHEN Xi , PATON R S , et al . Enzymatic catalysis of anti-Baldwin ring closure in polyether biosynthesis [J ] . Nature , 2012 , 483 ( 7389 ): 355 -U154.

LUHAVAYA H , DIAS M V , WILLIAMS S R , et al . Enzymology of pyran ring A formation in salinomycin biosynthesis [J ] . Angewandte Chemie (Weinheim an der Bergstrasse , Germany) , 2015 , 127 ( 46 ): 13826 - 13829 .

WANG Luoyi , PARNELL A , WILLIAMS C , et al . A Rieske oxygenase/epoxide hydrolase-catalysed reaction cascade creates oxygen heterocycles in mupirocin biosynthesis [J ] . Nature Catalysis , 2018 , 1 ( 12 ): 968 - 976 .

MAO Xuming , ZHAN Zhajun , GRAYSON M N , et al . Efficient biosynthesis of fungal polyketides containing the dioxabicyclo-octane ring system [J ] . Journal of the American Chemical Society , 2015 , 137 ( 37 ): 11904 - 11907 .

LIN Tzu-Shyang , CHIANG Yi-Ming , WANG C C . Biosynthetic pathway of the reduced polyketide product citreoviridin in Aspergillus terreus var. aureus revealed by heterologous expression in Aspergillus nidulans [J ] . Organic Letters , 2016 , 18 ( 6 ): 1366 - 1369 .

LIN Shuangjun , HORSMAN G P , SHEN Ben . Characterization of the epoxide hydrolase NcsF2 from the neocarzinostatin biosynthetic gene cluster [J ] . Organic Letters , 2010 , 12 ( 17 ): 3816 - 3819 .

ZOU Yi , GARCIA-BORRAS M , TANG Mancheng , et al . Enzyme-catalyzed cationic epoxide rearrangements in quinolone alkaloid biosynthesis [J ] . Nature Chemical Biology , 2017 , 13 ( 3 ): 325 - 332 .

SATO K , MINAMI A , OSE T , et al . Remarkable synergistic effect between MonBI and MonBII on epoxide opening reaction in ionophore polyether monensin biosynthesis [J ] . Tetrahedron Letters , 2011 , 52 ( 41 ): 5277 - 5280 .

YURKOVICH M E , TYRAKIS P A , HONG H , et al . A late-stage intermediate in salinomycin biosynthesis is revealed by specific mutation in the biosynthetic gene cluster [J ] . ChemBioChem , 2012 , 13 ( 1 ): 66 - 71 .

PISTORIUS D , LI Yanyan , SANDMANN A , et al . Completing the puzzle of aurachin biosynthesis in Stigmatella aurantiaca Sg a15 [J ] . Molecular BioSystems , 2011 , 7 ( 12 ): 3308 - 3315 .

BIS D M , BAN Y H , JAMES E D , et al . Characterization of the nocardiopsin biosynthetic gene cluster reveals similarities to and differences from the rapamycin and fk-506 pathways [J ] . ChemBioChem , 2015 , 16 ( 6 ): 990 - 997 .

WANG Bin , GUO Fang , REN Jinwei , et al . Identification of Alp1U and Lom6 as epoxy hydrolases and implications for kinamycin and lomaiviticin biosynthesis [J ] . Nature Communications , 2015 , 6 ( 1 ): 7674 .

ZHENG Qingfei , WANG Shoufeng , DUAN Panpan , et al . An α/β-hydrolase fold protein in the biosynthesis of thiostrepton exhibits a dual activity for endopeptidyl hydrolysis and epoxide ring opening/macrocyclization [J ] . Proceedings of the National Academy of Sciences of The United States Of America , 2016 , 113 ( 50 ): 14318 - 14323 .

WANG F , TAN K , BIGELOW L , et al . The crystal structure of an epoxide hydrolase from Streptomyces carzinostaticus subsp. neocarzinostaticus [DB/OL ] . 2014 . Protein Data Bank: http: //www. rcsb. org/structure/5F4Z http://www.rcsb.org/structure/5F4Z .

WANG F , TAN K , BIGELOW L , et al . Ensemble refinement of an epoxide hydrolase from Streptomyces carzinostaticus subsp. neocarzinostaticus [DB/OL ] . 2014 . Protein Data Bank: http: //www. rcsb. org/structure/4QA9 http://www.rcsb.org/structure/4QA9 .

TAN K , BIGELOW L , CLANCY S , et al . The crystal structure of an epoxide hydrolase from Streptomyces carzinostaticus subsp. neocarzinostaticus [DB/OL ] . 2012 . Protein Data Bank: http: //www. rcsb. org/structure/4I19 http://www.rcsb.org/structure/4I19 .

SCHULZ E C , WILMANNS M , HENDERSON S , et al . The crystal structure of Mycobacterial epoxide hydrolase A [DB/OL ] . 2016 . Protein Data Bank: http: //www. rcsb. org/structure/5CW2 http://www.rcsb.org/structure/5CW2 .

MOYNIE L , SCHNELL R , MCMAHON S A , et al . The AEROPATH project targeting Pseudomonas aeruginosa : crystallographic studies for assessment of potential targets in early-stage drug discovery [J ] . Acta Crystallographica Section F , 2013 , 69 : 25 - 34 .

DE OLIVEIRA G S , ADRIANI P P , RIBEIRO J A , et al . The molecular structure of an epoxide hydrolase from Trichoderma reesei in complex with urea or amide-based inhibitors [J ] . International Journal of Biological Macromolecules , 2019 , 129 : 653 - 658 .

WILSON C , DE OLIVEIRA G S , ADRIANI P P , et al . Structure of a soluble epoxide hydrolase identified in Trichoderma reesei [J ] . Biochimica et Biophysica Acta - Proteins and Proteomics , 2017 , 1865 ( 8 ): 1039 - 1045 .

BAHL C D , HVORECNY K L , BRIDGES A A , et al . Signature motifs identify an acinetobacter Cif virulence factor with epoxide hydrolase activity [J ] . The Journal of Biological Chemistry , 2014 , 289 ( 11 ): 7460 - 7469 .

SUN Zaibao , ZHANG Zhijun , LI Fulong , et al . One pot asymmetric synthesis of ( R )-phenylglycinol from racemic styrene oxide via cascade biocatalysis [J ] . ChemCatChem , 2019 , 11 ( 16 ): 3802 - 3807 .

YUAN Jifeng , LUKITO B R , LI Zhi . De novo biosynthesis of ( S )- and ( R )-phenylethanediol in yeast via artificial enzyme cascades [J ] . ACS Synthetic Biology , 2019 , 8 ( 8 ): 1801 - 1808 .

RINK R , FENNEMA M , SMIDS M , et al . Primary structure and catalytic mechanism of the epoxide hydrolase from Agrobacterium radiobacter AD1 [J ] . The Journal of Biological Chemistry , 1997 , 272 ( 23 ): 14650 - 14657 .

孔旭东 , 郁惠蕾 , 周佳海 , 等 . 环氧水解酶的结构基础及新酶开发 [J ] . 生物加工过程 , 2013 , 11 ( 1 ): 77 - 86 .

KONG Xudong , YU Huilei , ZHOU Jiahai , et al . Structure basis of EHs and development of novel EHs as biocatalyst [J ] . Chinese Journal of Bioprocess Engineering , 2013 , 11 ( 1 ): 77 - 86 .

ZOU Jinyu , HALLBERG B M , BERGFORS T , et al . Structure of Aspergillus niger epoxide hydrolase at 1.8 Å resolution: implications for the structure and function of the mammalian microsomal class of epoxide hydrolases [J ] . Structure , 2000 , 8 ( 2 ): 111 - 122 .

NARDINI M , RINK R , JANSSEN D B , et al . Structure and mechanism of the epoxide hydrolase from Agrobacterium radiobacter AD1 [J ] . Journal of Molecular Catalysis B: Enzymatic , 2001 , 11 ( 4/5/6 ): 1035 - 1042 .

HOPMANN K H , HALLBERG B M , HIMO F . Catalytic mechanism of limonene epoxide hydrolase, a theoretical study [J ] . Journal of the American Chemical Society , 2005 , 127 ( 41 ): 14339 - 14347 .

ARAND M , HALLBERG B M , ZOU Jinyu , et al . Structure of Rhodococcus erythropolis limonene-1,2-epoxide hydrolase reveals a novel active site [J ] . The EMBO Journal , 2003 , 22 ( 11 ): 2583 - 2592 .

李昆 , 杨国强 , 刘媛媛 , 等 . 手性双金属催化剂及其在不对称催化反应中的应用 [J ] . 有机化学 , 2013 , 33 ( 4 ): 749 - 759 .

LI Kun , YANG Guoqiang , LIU Yuanyuan , et al . Chiral polymetallic catalysts and their applications in asymmetric catalysis [J ] . Chinese Journal of Organic Chemistry , 2013 , 33 ( 4 ): 749 - 759 .

曹靖 . 大基团取代的末端手性环氧化物的制备及其聚合物的合成 [D ] . 湘潭 : 湘潭大学 , 2007 .

CAO Jing . The synthesis and polymerization of chiral terminal epoxides with bulky group [D ] . Xiangtan : Xiangtan University , 2007 .

张晓健 , 郑裕国 . 甘油原料转化生产手性环氧氯丙烷关键酶的开发 [J ] . 生物产业技术 , 2017 ( 6 ): 65 - 72 .

ZHANG Xiaojian , ZHENG Yuguo . Research and development on key enzymes for biosynthesis of chiral epichlorohydrin using glycerol [J ] . Biotechnology&Business , 2017 ( 6 ): 65 - 72 .

赵剑伟 . 转氨酶MVTA的克隆表达及其应用于级联催化合成手性 β -氨基醇和邻二醇的研究 [D ] . 太原 : 太原理工大学 , 2019 .

ZHAO Jianwei . Cloningand expression of ω -transaminase mvta applying in synthsis of chiral β -amino alcohols and vicinal diols via cascade catalysis [D ] . Taiyuan : Taiyuan University of Technology , 2019 .

吴群 , 邹树平 , 郑裕国 . 环氧化物水解酶在手性药物中间体合成中的应用 [J ] . 精细与专用化学品 , 2015 , 23 ( 6 ): 23 - 29 .

WU Qun , ZOU Shuping , ZHENG Yuguo . Applications of epoxide hydrolase in the synthesis of chiral drug intermediates [J ] . Fine and Special Chemicals , 2015 , 23 ( 6 ): 23 - 29 .

吴群 . 环氧化物水解酶分子改造及其催化拆分环氧氯丙烷的研究 [D ] . 杭州 : 浙江工业大学 , 2015 .

WU Qun . Molecular modification to epoxide hydrolase and its application in the resolution of epichlorohydrin [D ] . Hangzhou : Zhejiang University of Technology , 2015 .

JIANG Chengjun , HONG Huabin . A new practical synthesis of ethyl ( R )-(-)-4-cyano-3-hydroxybutyrate from ( S )-3-chloro-1,2-propanediol [J ] . Letters in Organic Chemistry , 2012 , 9 ( 7 ): 520 - 521 .

LIANG Youxiang , JIAO Song , WANG Miaomiao , et al . Overexpression of epoxide hydrolase in Rhodococcus ruber with high robustness for the synthesis of chiral epichlorohydrin [J ] . Process Biochemistry , 2019 , 79 : 49 - 56 .

ZOU Shuping , WANG Zhicai , QIN Chao , et al . Covalent immobilization of Agrobacterium radiobacter epoxide hydrolase on ethylenediamine functionalised epoxy supports for biocatalytical synthesis of ( R )-epichlorohydrin [J ] . Biotechnology Letters , 2016 , 38 ( 9 ): 1579 - 1585 .

JIA Xin , XU Yi , LI Zhi . Regio-and stereoselective concurrent oxidations with whole cell biocatalyst: simple and green syntheses of enantiopure 1,2-diols via oxidative kinetic resolution [J ] . ACS Catalysis , 2011 , 1 ( 6 ): 591 - 596 .

LI Keqiang , VIG S , UCKUN F M . Stereocontrolled synthesis of the tetrahydrofuran unit of annonaceous acetogenins [J ] . Tetrahedron Letters , 1998 , 39 ( 15 ): 2063 - 2066 .

HU Die , ZONG Xuncheng , XUE Feng , et al . Manipulating regioselectivity of an epoxide hydrolase for single enzymatic synthesis of ( R )-1,2-diols from racemic epoxides [J ] . Chemical Communications , 2020 , 56 ( 18 ): 2799 - 2802 .

SAINI P , KUMAR N , WANI S I , et al . Bioresolution of racemic phenyl glycidyl ether by a putative recombinant epoxide hydrolase from Streptomyces griseus NBRC 13350 [J ] . World Journal of Microbiology and Biotechnology , 2017 , 33 ( 5 ): 82 .

VAN LOO B , SPELBERG J H L , KINGMA J , et al . Directed evolution of epoxide hydrolase from A. radiobacter toward higher enantioselectivity by error-prone PCR and DNA shuffling [J ] . Chemistry & Biology , 2004 , 11 ( 7 ): 981 - 990 .

KO Myung Soo , LOVE J J . Step-wise directed evolution of an epoxide hydrolase against progressively larger non-natural substrates [J ] . The FASEB Journal , 2017 , 31 ( s1 ): 922 . 1-922 . 1 .

ZOU Shuping , ZHENG Yuguo , WU Qun , et al . Enhanced catalytic efficiency and enantioselectivity of epoxide hydrolase from Agrobacterium radiobacter AD1 by iterative saturation mutagenesis for ( R )-epichlorohydrin synthesis [J ] . Applied Microbiology and Biotechnology , 2018 , 102 ( 2 ): 733 - 742 .

SUN Zhoutong , LONSDALE R , WU Lian , et al . Structure-guided triple-code saturation mutagenesis: efficient tuning of the stereoselectivity of an epoxide hydrolase [J ] . ACS Catalysis , 2016 , 6 ( 3 ): 1590 - 1597 .

ZHENG Huabao , REETZ M T . Manipulating the stereoselectivity of limonene epoxide hydrolase by directed evolution based on iterative saturation mutagenesis [J ] . Journal of the American Chemical Society , 2010 , 132 ( 44 ): 15744 - 15751 .

ZONG Xuncheng , LI Chuang , XU Yaohui , et al . Substantially improving the enan tioconvergence of Pv EH1, a Phaseolus vulgaris epoxide hydrolase, towards m -chlorostyrene oxide by laboratory evolution [J ] . Microbial Cell Factories , 2019 , 18 ( 1 ): 1 - 8 .

LI Fulong , KONG Xudong , CHEN Qi , et al . Regioselectivity engineering of epoxide hydrolase: near-perfect enantioconvergence through a single site mutation [J ] . ACS Catalysis , 2018 , 8 ( 9 ): 8314 - 8317 .

JIN Huoxi , OUYANG Xiaokun , HU Zhongce . Enhancement of epoxide hydrolase production by 60 Co gamma and UV irradiation mutagenesis of Aspergillus niger ZJB-09103 [J ] . Biotechnology and Applied Biochemistry , 2017 , 64 ( 3 ): 392 - 399 .

LIANG Bo , HUANG Xuenian , TENG Yun , et al . Enhanced single-step bioproduction of the simvastatin precursor monacolin J in an industrial strain of Aspergillus terreus by employing the evolved lovastatin hydrolase [J ] . Biotechnology Journal , 2018 , 13 ( 6 ): 1800094 .

YU Da , WANG Jianbo , REETZ M T . Exploiting designed oxidase-peroxygenase mutual benefit system for asymmetric cascade reactions [J ] . Journal of the American Chemical Society , 2019 , 141 ( 14 ): 5655 - 5658 .

NIU Guoqing , ZHENG Jiazhen , TAN Huarong . Biosynthesis and combinatorial biosynthesis of antifungal nucleoside antibiotics [J ] . Science China Life Sciences , 2017 , 60 ( 9 ): 939 - 947 .

MOSS N A , SEILER G , LEÃO T F , et al . Nature's combinatorial biosynthesis produces Vatiamides A-F [J ] . Angewandte Chemie International Edition , 2019 , 58 ( 27 ): 9027 - 9031 .

LIU Song , ZHANG Xian , LIU Fei , et al . Designing of a cofactor self-sufficient whole-cell biocatalyst system for production of 1,2-amino alcohols from epoxides [J ] . ACS Synthetic Biology , 2019 , 8 ( 4 ): 734 - 743 .

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