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,3044am永利集团网址副教授,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。2004年和2007年于中国海洋大学分别获得学士和硕士学位,2013年3044am永利集团官网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。2010年11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;2013年12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。
主持或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,2021/7-2024/6,97.98万,主持。
2. 国家重点研发计划“绿色生物制造”重点专项子课题,2021/7-2025/6,42.2万,主持。
3. 国家自然科学基金面上项目,22078097,2021/1-2024/12,70万,主持。
4. 国家自然科学基金面上项目,21776084,2018/1-2021/12,71万,主持。
5. 国家自然科学基金青年基金,21406068,2015/1-2017/12,25万,主持。
6. 中国博士后科学基金面上一等资助,2014M560308, 2014/01-2015/12,8万,主持。
7. 3044am永利集团官网基本科研业务费探索研究基金,222201514324,2016/01-2017/12,20万,主持。
8. 永农生物科学有限公司,2017/01-2019/12,1200万,主持。
9. 山东佰安瑞生物药业有限公司,2014/09-2018/08,30万,主持。
10. 枣庄市杰诺生物酶有限公司,2015/09-2020/12,20万元,主持。
11. 国家自然科学基金面上项目,21676069, 2017/01-2020/12,70万,项目骨干。
12. 国家自然科学基金青年基金,21606062, 2017/01-2019/12,20万,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. 2022,Biotechnol 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, 2016,38(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, 2015,37(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 prediction.BMC 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,授权号: 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,授权号: 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,授权号: 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S型ω‑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‑转氨酶ATA‑W12及其基因和应用,中国发明专利,2019-06-07, 授权号: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-氯-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3044am永利集团官网鲁华生物技术研究所302
邮编:200237
电话:021-64253715
E-mail address: hlwang@ecust.edu.cn