王华磊
发布时间:2024-03-07   访问次数:15560


王华磊

  

  

生物学专业:博士生导师/硕士生导师

生物工程专业:博士生导师/硕士生导师

生物与医药专业(生物工程领域):博士生导师/硕士生导师


  

  

 

 王华磊,男,理学博士,4688美高梅集团唯一副教授,博士生导师。现任中国轻工业生物催化与智能制造重点实验室副主任,生物反应器工程国家重点实验室固定人员。20042007于中国海洋大学分别获得学士和硕士学位,2013年4688美高梅集团唯一生物化学与分子生物学专业博士毕业。主要研究方向为生物催化剂(酶)的高效开发、人工定制及其在手性药物中间体合成中的应用。201011月参与完成的工业酶制剂的创制与应用关键技术获上海市科技进步一等奖;201312月参与完成的定向转化多元醇的细胞催化剂创制及其应用关键技术获上海市技术发明一等奖。获上海生物工程学会“东富龙”生物工程优秀青年科学家奖。作为项目负责人主持国家自然科学青年基金(1项)、面上基金(2项)、中国博士后科学基金、国家重点研发计划“绿色生物制造”子课题任务(2项)及多项企业课题,总经费达1000余万元。在Angew. Chem. Int. Ed.Chemical Communication, Catalysis Science & Technology, Applied and Environmental Microbiology等学术期刊发表SCI论文40余篇,申请中国发明专利20余项,已授权9项。

  

研究方向:

1. 以酶资源多样性、酶催化机理、理性设计方法学为研究内容的生物催化剂高效创制。

2. 以“高值化”产品为导向、基于逆合成生物催化技术的手性药物中间体绿色高效合成工艺开发。

  

主持参加的科研项目或基金

1. 国家重点研发计划“绿色生物制造”重点专项子课题,2021/7-2024/697.98万,主持。

2. 国家重点研发计划“绿色生物制造”重点专项子课题,2021/7-2025/642.2万,主持。

3. 国家自然科学基金面上项目,220780972021/1-2024/1270万,主持。

4. 国家自然科学基金面上项目,217760842018/1-2021/1271主持。

5. 国家自然科学基金青年基金,214060682015/1-2017/1225主持。

6. 中国博士后科学基金面上一等资助,2014M560308 2014/01-2015/128主持。

7. 4688美高梅集团唯一基本科研业务费探索研究基金,2222015143242016/01-2017/1220万,主持。

8. 永农生物科学有限公司,2017/01-2019/121200主持。

9. 山东佰安瑞生物药业有限公司,2014/09-2018/0830主持。

10. 枣庄市杰诺生物酶有限公司,2015/09-2020/1220万元主持。

11. 国家自然科学基金面上项目,216760692017/01-2020/1270项目骨干。

12. 国家自然科学基金青年基金,216060622017/01-2019/1220,项目骨干

  

教学:

本科课程《酶工程》《生物反应工程原理》《微生物学实验II》《食品原料安全控制》

研究生课程《酶学与生物催化》

  

代表性论文*通讯作者):   

1. Wenjie Ye, Yuxin Zhang, Yilin Wang, Jingwen Xie, Yan Liu, Lin Yang, Hualei Wang*, Dongzhi Wei. Engineering a Medium-chain Alcohol Dehydrogenase for Efficient Synthesis of (S)-N-Boc-3-pyrrolidinol by Adjusting the Conformational Dynamics of Loops. 2022, ChemCatChem, DOI:10.1002/cctc.202201175.

2. Ke Zhang, Tingze Pan, Liuzhu Wang, Hualei Wang*, Yuhong Ren & Dongzhi Wei. Screening and characterization of a nitrilase with significant nitrile hydratase activity. 2022Biotechnol Lett 44, 1163–1173.

3. Lin Yang, Kaiyue Zhang, Meng Xu, Youyu Xie, Xiangqi Meng, Hualei Wang,* and Dongzhi Wei*. Mechanism-Guided Computational Design of ω-Transaminase by Reprograming of High-Energy-Barrier Steps. Angew. Chem. Int. Ed. 2022, 61(52):e202212555.

4. Xiangxiang Wang, Youyu Xie, Zhicai Wang, Ke Zhang, Hualei Wang*, Dongzhi Wei. Efficient Synthesis of (S)-1-Boc-3-aminopiperidine in a Continuous Flow System Using Transaminase-Immobilized Amino-Ethylenediamine-Modified Epoxide Supports. Organic Process Research & Development, 2022, 26, 5, 1351–1359 

5. Ling He, Wenjie Ye, Youyu Xie, Qinghai Liu, Hualei Wang*, and Dongzhi Wei. Efficient Biocatalytic Synthesis of (R)-2-Chloro-1-(3,4-difluorophenyl)ethanol by the Short-Chain Dehydrogenase PpKR8 from Paraburkholderia phymatum STM815. Organic Process Research & Development, 2022, 26, 2, 278–287. 

6. Youyu Xie,# Jiguo Wang,# Lin Yang, Wei Wang, Qinghai Liu, Hualei Wang,* and Dongzhi Wei. The identification and application of a robust -transaminase with high tolerance of substrate and isopropylamine from a directed soil metagenome. Catalysis Science & Technology, 2022, 12, 2162-2175.

7. Lin Yang, Yiping Zhang, Yan Liu, Dongzhi Wei and Hualei Wang*. Highly efficient synthesis of pharmaceutically relevant chiral 3-N-substituted-azacyclic alcohols using two enantiocomplementary short chain dehydrogenases[J]. Biochemical Engineering Journal, 2021, 178, 1-9.

8. Liuzhu Wang, Yangyang Sun, Shiqing Diao, Shuiqin Jiang, Hualei Wang*, Dongzhi Wei. Rational hinge engineering of carboxylic acid reductase from Mycobacterium smegmatis enhances its catalytic efficiency. Biotechnology Journal, 2022, 17(2):e2100441. 

9. Xiangqi Meng, Lin Yang, Yan Liu, Hualei Wang, * Yaling Shen, Dongzhi Wei*. Identification and Rational Engineering of a High Substrate-Tolerant Leucine Dehydrogenase Effective for the Synthesis of L-tert-Leucine. ChemCatChem, 2021, 13(14), 3340-3349.

10. Liuzhu Wang,# Shiqing Diao,# Yangyang Sun, Shuiqin Jiang, Yan Liu, Hualei Wang* and Dongzhi Wei*. Rational engineering of Acinetobacter tandoii glutamate dehydrogenase for asymmetric synthesis of L-homoalanine through biocatalytic cascades. Catalysis Science & Technology, 2021,11, 4208-4215.

11. Youyu Xie, Feng Xu, Lin Yang, He Liu, Xiangyang Xu, Hualei Wang* and Dongzhi Wei*. Engineering the large pocket of an (S)-selective transaminase for asymmetric synthesis of (S)-1-amino-1-phenylpropane. Catalysis Science & Technology, 2021,11, 2461-2470. 出版时间:2021.01.29

12. Youyu Xie, Feng Xu, Lin Yang, He Liu, Xiangyang Xu, Hualei Wang*and  Dongzhi Wei*. Engineering the large pocket of an (S)-selective transaminase for asymmetric synthesis of (S)-1-amino-1-phenylpropane. Catalysis Science & Technology. 2021,DOI:10.1039/D0CY02426K.

13. Zhi Chen, Hualei Wang*, Lin Yang, Shuiqing Jiang, Dongzhi Wei*, et al. Significantly enhancing the stereoselectivity of a regioselective nitrilase for production of (S)-3-cyano-5-methylhexanoic acid using MM/PBSA method. Chem. Commun., 2021,57, 931-934.

14. Zeyu Yang, Wenjie Ye, Youyu Xie, Qinghai Liu, Rong Chen, Hualei Wang*, and Dongzhi Wei. Efficient Asymmetric Synthesis of Ethyl (S)-4-Chloro-3-hydroxybutyrate Using Alcohol Dehydrogenase SmADH31 with High Tolerance of Substrate and Product in a Monophasic Aqueous System.Org. Process Res. Dev. 2020, 24, 6, 1068–1076

15. Zeyu Yang, Hengwei Fu, Wenjie Ye, Youyu Xie, Qinghai Liu, Hualei Wang*, Dongzhi Wei*. Efficient asymmetric synthesis of chiral alcohols using high 2-propanol tolerance alcohol dehydrogenase SmADH2 via an environmentally friendly TBCR system. Catalysis Science & Technology, 2020, 10: 70-78.

16. Haiyang Fan, Lifeng Chen, Huihui Sun, Hualei Wang*, Qinghai Liu, Yuhong Ren, Dongzhi Wei. Characterization of a novel nitrilase, BGC4, from Paraburkholderia graminis showing wide-spectrum substrate specificity, a potential versatile biocatalyst for the degradation of nitriles. Biotechnology Letters, 2017, 39(11): 1725–1731.

17. Haiyang Fan, Lifeng Chen, Huihui Sun, Hualei Wang*, Qinghai Liu, Yuhong Ren, Dongzhi Wei. Development of nitrilase-mediated process for phenylacetic acid production from phenylacetonitrile. Chemical Papers, 2017, 71(10): 1985–1992.

18. Haiyang Fan, Lifeng Chen, Huihui Sun, Hualei Wang*, Yuhong Ren, Dongzhi Wei. A novel nitrilase from Ralstonia eutropha H16 and its application to nicotinic acid production. Bioprocess and Biosystems Engineering, 2017, 40(8):1271-1281.

19. Lifeng Chen, Haiyang Fan, Yiping Zhang, Wei Wei, Jinping Lin, Dongzhi Wei, Hualei Wang*. Enhancement of ethyl (S)-4-chloro-3-hydroxybutanoate production at high substrate concentration by in situ resin adsorption. Journal of biotechnology, 2017, 251:68-75.

20. Lifeng Chen, Yiping Zhang, Haiyang Fan, Kai Wu, Jinping Lin, Hualei Wang*, Dongzhi Wei. Efficient bioreductive production of (R)-N-Boc-3-hydroxypiperidine by a carbonyl reductase. Catalysis Communications, 2017, 97:5-9.

21. Lifeng Chen, Haiyang Fan, Yiping Zhang, Kai Wu, Hualei Wang*, Jinping Lin, Dongzhi Wei. Development of a practical biocatalytic process for (S)-N-Boc-3-hydroxypiperidine synthesis. Tetrahedron Letters, 2017, 58(16):1644–1650.

22. Yiping Zhang, Hualei Wang*, Lifeng Chen, Kai Wu, Jingli Xie, Dongzhi Wei. Efficient production of ethyl (R)-4-chloro-3-hydroxybutanoate by a novel alcohol dehydrogenase from Lactobacillus curieae S1L19. Journal of Molecular Catalysis B: Enzymatic. 2016, 134:51-60

23. Wenyuan Gao, Haiyang Fan, Lifeng Chen, Hualei Wang*, Dongzhi Wei. Efficient kinetic resolution of secondary alcohols using an organic solvent-tolerant esterase in non-aqueous medium. Biotechnology Letters. 2016, 38(7):1165-1171

24. Kai Wu, Hualei Wang#*, Lifeng Chen, Haiyang Fan, Zhiqiang Zhao, Dongzhi Wei*. Practical two-step synthesis of enantiopure styrene oxide through an optimized chemoenzymatic approach.  Applied Microbiology and Biotechnology. 2016, 100(20): 8757-8767

25. Zhiqiang Zhao, Hualei Wang*, Yiping Zhang, Lifeng Chen, Kai Wu, Dongzhi Wei. Cloning and characterization of three ketoreductases from soil metagenome for preparing optically active alcohols. Biotechnology Letters. 2016, 38(10):1799-1808

26. Wenyuan Gao, Kai Wu, Lifeng Chen, Haiyang Fan, Zhiqiang Zhao, Bei Gao, Hualei Wang*, Dongzhi Wei*. A novel esterase from a marine mud metagenomic library for biocatalytic synthesis of short-chain flavor esters. Microbial Cell Factories, 2016, 15:41.

27. Kai Wu, Lifeng Chen, Haiyang Fan, Zhiqiang Zhao, Hualei Wang*, Dongzhi Wei*. Synthesis of enantiopure epoxide by ‘one pot’ chemoenzymatic approach using a highly enantioselective dehydrogenase. Tetrahedron Letters, 2016, 57(8):899-904.

28. Huihui Sun, Wenyuan Gao, Hualei Wang*, Dongzhi Wei. Expression, characterization of a novel nitrilase PpL19 from Pseudomonas psychrotolerans with S-selectivity toward mandelonitrile present in active inclusion bodies. Biotechnology letters, 201638(3):455-461

29. Hualei Wang, Haiyang Fan, Huihui Sun, Li Zhao, Dongzhi Wei*. Process development for production of (R)-(-)-mandelic acid by recombinant Escherichia coli cells harboring nitrilase from Burkholderia cenocepacia J2315. Organic Process Research & Development, 2015,19(12),2010-2016

30. Hualei Wang, Wenyuan Gao, Huihui Sun, Lifeng Chen, Lujia Zhang, Xuedong Wang*, Dongzhi Wei*. Protein engineering of nitrilase from Burkholderia cenocepacia J2315 for efficient and enantioselective production of (R)-o-chloromandelic acid. Applied and Environmental Microbiology, 2015, 81(24):8469-8477.

31. Huihui Sun, Hualei Wang*, Wenyuan Gao, Lifeng Chen, Kai Wu, Dongzhi Wei*. Directed evolution of nitrilase PpL19 from Pseudomonas psychrotolerans L19 and identification of enantiocomplementary mutants toward mandelonitrile. Biochemical and Biophysical Research Communications, 2015, 468(4):820-825.

32. Huihui Sun, Wenyuan Gao, Haiyang Fan, Hualei Wang*, Dongzhi Wei. Cloning, purification and evaluation of the enzymatic properties of a novel arylacetonitrilase from Luminiphilus syltensis NOR5-1B: a potential biocatalyst for the synthesis of mandelic acid and its derivatives. Biotechnology letters, 201537(8):1655–1661.

33. Kai Wu, Hualei Wang*, Huihui Sun, Dongzhi Wei*. Efficient kinetic resolution of phenyl glycidyl ether by a novel epoxide hydrolase from Tsukamurella paurometabola. Applied Microbiology and Biotechnology, 2015, 99(22):9511-9521

34. Hualei Wang, Huihui Sun, Wenyuan Gao, Dongzhi Wei*. Efficient production of (R)-o-chloromandelic acid by recombinant Escherichia coli cells harboring nitrilase from Burkholderia cenocepacia J2315. Organic Process Research & Development, 2014, 18(6):767–773.

35. Hualei Wang, Guinan Li, Mingyang Li, Dongzhi Wei*, Xuedong Wang*. A novel nitrilase from Rhodobacter sphaeroides LHS-305-cloning, heterologous expression and biochemical characterization. World Journal of Microbiology and Biotechnology, 2014, 30(1):245-252.

36. Hualei Wang, Huihui Sun, Dongzhi Wei*. Discovery and characterization of a highly efficient enantioselective mandelonitrile hydrolase from Burkholderia cenocepacia J2315 by phylogeny-based enzymatic substrate specificity predictionBMC Biotechnology, 2013, 13:14.

37. Kefeng Ni, Hualei Wang(并列第一作者), Li Zhao, Minjie Zhang, Siyuan Zhang, Yuhong Ren*, Dongzhi Wei*. Efficient production of (R)-(-)-mandelic acid in biphasic system by immobilized recombinant E.coli. Journal of Biotechnology, 2013, 167(4):433-440.

38. Shuiqin Jiang, Lujia Zhang*, Zhiqiang Yao, Bei Gao, Hualei Wang, Xiangzhao Mao, Dongzhi Wei*. Switching a nitrilase from Syechocystis sp. PCC6803 to a nitrile hydratase by rationally regulating reaction pathways. Catalysis Science & Technology, 2017, 7, 1122-1128.

39. Jian Qiu, Erzheng Su*, Hualei Wang, Wenwen Cai, Wei Wang, Dongzhi Wei*. Cloning, overexpression, and characterization of a high enantioselective nitrilase from Sphingomonas wittichii RW1 for asymmetric synthesis of (R)-phenylglycine. Applied Biochemistry and Biotechnology, 2014, 173(2):365-377.

40. Lujia Zhang, Bo Yin, Chao Wang, Shuiqin Jiang, Hualei Wang, Dongzhi Wei*, Y Adam Yuan*. Structural insights into enzymatic activity and substrate specificity determination by a single amino acid in nitrilase from Syechocystis sp. PCC6803.  Journal of Structural Biology, 2014, 188(2):93-101.

41. Kefeng Ni, Xu Zhou, Li Zhao, Hualei Wang, Yuhong Ren, Dongzhi Wei*. Magnetic Catechol-Chitosan with Bioinspired Adhesive Surface: Preparation and Immobilization of omega-Transaminase. Plos One, 2012, 7(7): e41101

  

发明专利:

1. 王华磊,魏东芝,王留柱,一种催化活性提高的羧酸还原酶突变体及其编码基因、基因工程菌以及应用,中国发明专利,2021-07-27,申请号:CN202110852740.8

2. 魏东芝王华磊刁诗晴一种谷氨酸脱氢酶突变体及其编码基因、基因工程菌以及在制备L-2-氨基丁酸中的应用,中国发明专利,2021-07-27,申请号: CN202110334184.5

3. 王华磊, 魏东芝, 孟祥奇一种亮氨酸脱氢酶突变体及其编码基因、基因工程菌以及在制备L-叔亮氨酸中的应用,中国发明专利,2021-07-13授权: ZL 202110455494.2

4. 王华磊,魏东芝,吴承骏, 刘清海, 张舰,罗中华, 张长雷Glu/Leu/Phe/Val 脱氢酶突变体及其在制备 L-草铵膦中的应用,中国发明专利,2021-04-29,申请号:CN202110475238.X

5. 魏东芝,王华磊,吴承骏, 刘清海, 张舰,罗中华, 张长雷D-氨基酸氧化酶突变体及其在制备 L-草铵膦中的应用,中国发明专利,2021-04-29,申请号:CN202110475247.9

6. 王华磊, 魏东芝, 杨泽宇一种活性和立体选择性提高的醇脱氢酶突变体及其重组载体、基因工程菌以及应用,中国发明专利,2021-03-19申请号: CN202011578803.7

7. 王华磊,魏东芝,吴承骏, 刘清海, 罗中华, 张长雷利用生物多酶偶联法制备L-草铵膦的方法,中国发明专利,2020-12-17授权号ZL 202011496575 .9

8. 魏东芝, 王华磊, 吴承骏, 刘清海, 罗中华, 张长雷利用生物多酶偶联法制备L-草铵膦的方法,中国发明专利,2020-12-17授权: ZL 202011491692.6

9. 王华磊, 魏东芝, 谢有余一种ω-转氨酶及其突变体、重组质粒、基因工程菌及其应用,中国发明专利,2020-11-25授权: ZL 202011346097.3

10. 魏东芝,徐向阳,宋在伟,王华磊,一种生物法制备苯乙酸的方法,中国发明专利,2020-10-16授权号ZL 201611110169.8

11. 魏东芝王华磊汪湘湘,一种填充床连续流不对称合成(S)-1-Boc-3-氨基哌啶的方法,中国发明专利,2020-07-09 申请号:CN202010659240.8

12. 王继国王华磊,刘清海,魏东芝,一种Sω转氨酶高活性突变体,中国发明专利,2020.01.21,申请号:202010072818.X

13. 王华磊,谢有余,王继国,范海洋,魏东芝,一种S型的ω氨酶ATAW12及其基因和应用,中国发明专利,2019-06-07, 授权ZL 201611055835.2

14. 王华磊,张一平,魏东芝,一种醇脱氢酶LC3及其基因和应用,中国发明专利,2019-6-7, 授权号ZL 201610066375.7

15. 王华磊,高文渊,魏东芝,酯酶est4、酯酶EST4、重组质粒和基因工程菌株及其应用,中国发明专利, 2018-3-23, 授权号ZL 201510342723.4

16. 王华磊,吴锴,魏东芝,一种环氧化物水解酶及其编码基因和应用,中国发明专利,2018-3-6授权号ZL 201410175055.8

17. 魏东芝, 许向阳, 宋在伟, 王华磊一种生物法合成(R)邻氯扁桃酸的方法,中国发明专利,2017-05-17申请号: CN201611110170.0

18. 王华磊, 范海洋, 任宇红, 魏东芝一种生物法合成(R)-(-)-扁桃酸的方法,中国发明专利,2015-10-14申请号: CN201510334809.2

19. 王华磊, 陈利锋, 魏东芝一种不对称转化制备(S)-4--3-羟基丁酸乙酯的重组大肠杆菌及其应用,中国发明专利, 2015-05-27,申请号: CN201510098687.1

20. 任宇红, 魏东芝, 倪克奉, 王华磊, 赵莉, 张敏洁一种磁性固定化细胞及其制备方法和应用,中国发明专利,2013-10-09申请号: CN201310295739.5

 

联系方式: 

上海市梅陇路130号4688美高梅集团唯一鲁华生物技术研究所302

邮编:200237

电话:021-64253715

E-mail address: hlwang@ecust.edu.cn