吴中柳 职 务: 职 称:研究员 学 历:博士研究生
电 话:028-82890423, 028-82890434 传 真: 通讯地址:四川省成都市人民南路四段9号
邮政编码:610041 电子邮件:wuzhl@cib.ac.cn

个人简历

      吴中柳研究员,女,1975年6月生。2003年毕业于中国科学院上海有机化学研究所生物有机化学国家重点实验室,获理学博士学位。现任中国科学院成都生物研究所应用与环境微生物研究中心研究员,博士生导师。入选2008年度四川省杰出青年学科带头人。目前以第一作者或者通讯作者在国际知名学术杂志上发表SCI研究论文60余篇,论文被引用超过1000次(根据ResearchGate统计)。已授权发明专利14项。

研究方向

      1、高效高选择性功能酶的筛选、表达和分子改造;  

      2、新型多酶生物催化体系及化学-酶偶联体系的设计和构建; 

      3、高值手性化合物的酶催化合成新方法和新工艺研究;  

      4、生物催化法构建多样性的活性分子库和新型类药分子。  

        

      实验室构建了高效、高选择性的酶库和工具箱,主要涉及环氧化酶、细胞色素P450酶、羰基还原酶,烯烃还原酶等多种氧化还原酶类;构建了成熟的高通量筛选平台和蛋白质工程改造技术平台,开展酶蛋白及突变体的结构功能关系研究,实现生物催化剂的设计定制。 

        

      招收有机化学、微生物学、分子生物学、酶工程等相关学科硕士/博士研究生 

        

      课题组网页: 

      http://www.cib.ac.cn/yjxt/sjyjjg/yyyhjwswyjzx_103422/yjtz_103423/wzlyjytz/ 

社会任职及荣誉(含获奖)

     
     

承担科研项目情况

      国家自然科学基金(2008-20102011-20132014-2017&2016-2019 

      科技部科技重大专项,科技部中国越南政府间国际合作 

      中国科学院知识创新工程重大项目专题  

      中科院院部署项目,中科院STS项目 

      四川省青年科技基金 ,四川省科技基金,企业横向委托项目等 

代表论著

      1. Cui, C.; Guo, C.; Lin, H.; Ding, Z.-Y.; Liu, Y.; Wu, Z.-L.* Functional characterization of an (R)-selective styrene monooxygenase from streptomyces sp. NRRL S-31. Enzyme and Microbial Technology, 2020, DOI : 10.1016/j.enzmictec.2019.109391

      2. Li, T.-B.; Zhao, F.-J.; Liu, Z.-C.; Jin, Y.; Liu, Y.; Pei, X.-Q.; Zhang, Z.-G.; Wang, G.-G*.; Wu, Z.-L.* Structure-guided engineering of ChKRED20 from Chryseobacterium sp. CA49 for asymmetric reduction of aryl ketoesters. Enzyme and Microbial Technology, 2019, 125: 29-36.

      3. Ren, Z.-Q.; Liu, Y.; Pei, X.-Q.; Wu, Z.-L.* Stereoselective bioreduction of ethyl 3-oxo-3-(2-thienyl) propanoateusing theshort-chain dehydrogenase/reductase ChKRED12. J. Microbiol. Biotechnol. 2018, DOI : 10.4014/jmb.1805.04058

      4. Pu, W.; Cui, C.; Guo, C.; Wu, Z.-L.* Characterization of two styrene monooxygenases from marine microbes. Enzyme and Microbial Technology, 2018, 112:29-34.

      5. Zhao, F.-J.; Jin, Y.; Liu, Z.-C.; Guo, C.; Li, T.-B.; Li, Z.-Y.; Wang G.-G.*; Wu, Z. -L*. Crystal structure and iterative saturation mutagenesis of ChKRED20 for expanded catalytic scope. Appl Microbiol Biotechnol. 2017, 101(23–24): 8395–8404.

      6. Guo, C.; Wu, Z.-L.* Construction and functional analysis of a whole-cell biocatalyst based on CYP108N7. Enzyme and Microbial Technology, 2017, 106:28-34.

      7. Liu, Y.-C.; Guo, C.; Liu, Y.; Wang, H.-B.; Wu, Z.-L.* Enzymatic cascades for the stereo-complementary epimerisation of in situ generated epoxy alcohols. Org. Biomol. Chem., 2017, 15, 2562-2568.

      8. Li, C.; Liu, Y.; Pei, X.-Q.; Wu, Z.-L.* Stereo-complementary bioreduction of saturated N-heterocyclic ketones, Process Biochem., 2017, 56, 90-97.

      9. Zhao, F.-J.; Liu, Y.; Pei, X.-Q.; Guo, C.; Wu, Z.-L.* Single mutations of ketoreductase ChKRED20 enhance the bioreductive production of (1S)-2-chloro-1-(3, 4-difluorophenyl) ethanol. Appl Microbiol Biotechnol, 2017,101(5):1945-1952.

      10. Liu, Y.; Liu, Y.-C; Wu, Z.-L*. Asymmetric bio epoxidation catalyzed with the styrene monooxygenase from Pseudomonas sp. LQ26. Bioresour. Bioprocess. 2016, 100 (8): 3567-3575.

      11. Xu, G.-P.; Wang, H.-B., Wu, Z.-L*. Efficient bioreductive production of (S)-N-Boc-3-hydroxypiperidine using ketoreductaseChKRED03. Process Biochem. 2016, 51: 881-885.

      12. Pei, X.-Q.; Xu, M.-Y.; Wu, Z.-L.* Two “classical” Old Yellow Enzymes from Chryseobacterium sp. CA49: broad substrate specificity of Chr-OYE1 and limited activity of Chr-OYE2. J. Mol. Catal. B: Enzym. 2016, 123:91-99.

      13. Zhao, F.-J.; Pei, X.-Q.; Ren, Z.-Q.; Wu, Z.-L.* Rapid asymmetric reduction of ethyl 4-chloro-3-oxobutanoate using a thermostabilized mutant of ketoreductase ChKRED20. Appl Microbiol Biotechnol. 2016. 100 (8): 3567-3575.

      14. Li, J.-J.; Pei, X.-Q.; Zhang, S.-B.; Wu, Z.-L*. Improving the thermostability of feruloyl esterase by DNA shuffling and site-directed mutagenesis. Process Biochem. 2015, 50: 1783-1787.

      15. Li, J.-J.; Yi, Z.-L.; Pei, X.-Q.; Wu, Z.-L*. Removal of the free cysteine residue reduces irreversible thermal inactivation of Feruloyl Esterase: evidence from circular dichroism and fluorescence spectra. Acta Biochimica et Biophysica Sinica. 2015, 47(8):612-619.

      16. Liu, Y.-C; Wu, Z.-L*. Switchable asymmetric bio-epoxidation of a,b-unsaturated ketones. Chem. Commun. 2016, 52(6), 1158 – 1161.

      17. Ren, Z.-Q; Liu, Y.; Pei, X.-Q; Wang H.-B.; Wu, Z.-L*. Bioreductive production of enantiopure (S)-duloxetine intermediatescatalyzed with ketoreductase ChKRED15. J. Mol. Catal. B: Enzym. 2015, 113,76–81.

      18. Liu, Y.-C; Liu, Y.; Wu, Z.-L*. Synthesis of enantiopure glycidol derivatives via a one-pot two-step enzymatic cascade. Org. Biomol. Chem., 2015, 13, 2146–2152

      19. Xu, M.-Y., Pei, X.-Q., Wu, Z.-L.* Identification and characterization of a novel "thermophilic-like" Old Yellow Enzyme from the genome of Chryseobacterium sp. CA49. J. Mol. Catal. B: Enzym. 2014, 108, 64-71.

      20. Tang, T.-X.; Liu, Y; Wu, Z.-L.* Characterization of a robust anti-Prelog short-chain dehydrogenase/reductase ChKRED20 fromChryseobacterium sp. CA49. J. Mol. Catal. B: Enzym. 2014, 105, 82-88.

      21. Liu, Y., Tang, T.-X., Pei, X.-Q., Zhang, C., Wu, Z.-L.* Identification of ketone reductase ChKRED20 from the genome ofChryseobacterium sp. CA49 for highly efficient anti-Prelog reduction of 3,5-bis(trifluoromethyl)acetophenone. J. Mol. Catal. B: Enz. 2014, 102(4), 1-8.

      22. 18. Wang, H.-B., Pei, X.-Q.; Wu, Z.-L.* An enoate reductase Acrh-OYE4 from Achromobacter sp. JA81: Characterization and application in asymmetric bioreduction of C=C bonds. Appl. Microbiol. Biotechnol. 2014, 98(2), 705-715.

      23. Yi, Z.-L.; Zhang, S.-B.*; Pei, X.-Q.; Wu, Z.-L.* Design of mutants for enhanced thermostability of b-glycosidase BglY fromThermus thermophilus. Bioresour. Technol. 2013, 129, 629-633.

      24. Lin, H.; Tang, D.-F.; Ahmed, A. A. Q.; Liu, Y.; Wu, Z.-L.* Mutations at the putative active cavity of styrene monooxygenase: enhanced activity and reversed enantioselectivity. J. Biotechnol. 2012, 161, 235-241.

      25. Zhang, S.-B.; Pei, X.-Q.; Wu, Z.-L.* Multiple amino acid substitutions significantly improve the thermostability of feruloyl esterase A from Aspergillus niger. Bioresour. Technol. 2012, 117, 140-147.

      26. Liu, Y.-J.; Pei, X.-Q.; Lin, H.; Gai, P.; Liu, Y.-C.; Wu, Z.-L.* Asymmetric bioreduction of activated alkenes by a novel isolate ofAchromobacter species producing enoate reductase. Appl. Microbiol. Biotechnol. 2012, 95(3), 635-645.

      27. Zhang, S.-B.; Ma, X.-F.; Pei, X.-Q.; Liu, J.-Y.; Shao, H.-W.*, Wu, Z.-L.* A practical high-throughput screening system for feruloyl esterases: substrate design and evaluation. J. Mol. Catal. B: Enzym. 2012, 74, 36-40.

      28. Lin, H.; Liu, J.-Y.; Wang, H.-B.; Ahmed, A. A. Q.; Wu, Z.-L.* Biocatalysis as an alternative for the production of chiral epoxides: a comparative review. J. Mol. Catal. B: Enzym. 2011, 72(3-4), 77-89. (Invited review)

      29. Tang, C.-G.; Lin, H.; Zhang, C.; Liu, Z.-Q.; Yang, T.; Wu, Z.-L.* Highly enantioselective bioreduction of N-methyl-3-oxo-3- (thiophen-2-yl) propanamide for the production of (S)-duloxetine. Biotechnol. Lett. 2011, 33(7), 1435-1440.

      30. Lin, H.; Liu, Y.; Wu, Z.-L.* Highly diastereo- and enantio-selective epoxidation of secondary allylic alcohols catalyzed by styrene monooxygenase. Chem. Commun., 2011, 47, 2610-2612.

      31. Lin, H.; Liu, Y.; Wu, Z.-L.* Asymmetric epoxidation of styrene derivatives by styrene monooxygenase from Pseudomonas sp. LQ26: effects of a- and b-substituents. Tetrahedron: Asymmetry, 2011, 22, 134-137.

      32. Yi, Z.-L.; Pei, X.-Q.; Wu, Z.-L.* Introduction of glycine and proline residues onto protein surface increases the thermostability of endoglucanase CelA from Clostridium thermocellum. Bioresour. Technol. 2011, 102(3), 3636–3638

      33. Pei, X.-Q.; Yi, Z.-L.; Tang, C.-G.; Wu, Z.-L.* Three amino acid changes contribute markedly to the thermostability of b-glucosidase BglC from Thermobifida fusca. Bioresour. Technol. 2011, 102(3), 3337–3342.

      34. Qaed, A. A.; Lin, H.; Tang, D.-F.; Wu, Z.-L.* Rational design of styrene monooxygenase mutants with altered substrate preference. Biotechnol. Lett. 2011, 33, 611-616.

      35. Zhang, S.-B.; Wu, Z.-L.* Identification of amino acid residues responsible for increased thermostability of feruloyl esterase A from Aspergillus niger using the PoPMuSiC algorithm. Bioresour. Technol. 2011, 102 (2), 2093–2096.

      36. Lin, H.; Qiao, J.; Liu, Y.; Wu, Z.-L.* Styrene monooxygenase from Pseudomonas sp. LQ26 catalyzes the asymmetric epoxidation of both conjugated and unconjugated alkenes. J. Mol. Catal. B: Enzym. 2010, 67(3-4), 236-241.

      37. Zhang, Z.-G.; Yi, Z.-L.; Pei, X.-Q.; Wu, Z.-L.* Improving the thermostability of Geobacillus stearothermophilus xylanase XT6 by directed evolution and site-directed mutagenesis. Bioresour. Technol. 2010, 101(23), 9272-9278.

      38. Yi, Z.-L.; Wu, Z.-L.* Mutations from a family-shuffling-library reveal amino acid residues responsible for the thermostability of endoglucanase CelA from Clostridium thermocellum Biotechnol. Lett. 2010, 32(12), 1869-1875.

      39. Tang, Z., Salamanca-Pinzon, S.G., Wu, Z.L., Xiao, Y., Guengerich, F.P., Human cytochrome P450 4F11: Heterologous expression in bacteria, purification, and characterization of catalytic function. Arch. Biochem. Biophys. 2010, 494(1), 86-93.

      40. Wu, Z.-L.*; Qiao, J.; Zhang, Z.-G.; Guengerich, F.P.; Liu, Yan; Pei, X.-Q. Enhanced bacterial expression of several mammalian cytochrome P450s by codon optimization and chaperone coexpression. Biotechnol. Lett. 2009, 31(10), 1589-1593.

      41. Zhang, Z.-G.; Liu, Y.; Guengerich, F.P.; Matse, J.H.; Chen J.; Wu, Z.-L.* Identification of amino acid residues involved in 4-chloroindole 3-hydroxylation by cytochrome P450 2A6 using screening of random libraries. J. Biotechnol. 2009, 139(1), 12-18.