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个人简介

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。 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/

研究领域

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。

承担科研项目情况 国家自然科学基金(2008-2010,2011-2013,2014-2017&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

近期论文

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1.Cui,C.;Guo,C.;Lin,H.;Ding,Z.-Y.;Liu,Y.;Wu,Z.-L.*Functionalcharacterizationofan(R)-selectivestyrenemonooxygenasefromstreptomycessp.NRRLS-31.EnzymeandMicrobialTechnology,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-guidedengineeringofChKRED20fromChryseobacteriumsp.CA49forasymmetricreductionofarylketoesters.EnzymeandMicrobialTechnology,2019,125:29-36. 3.Ren,Z.-Q.;Liu,Y.;Pei,X.-Q.;Wu,Z.-L.*Stereoselectivebioreductionofethyl3-oxo-3-(2-thienyl)propanoateusingtheshort-chaindehydrogenase/reductaseChKRED12.J.Microbiol.Biotechnol.2018,DOI:10.4014/jmb.1805.04058 4.Pu,W.;Cui,C.;Guo,C.;Wu,Z.-L.*Characterizationoftwostyrenemonooxygenasesfrommarinemicrobes.EnzymeandMicrobialTechnology,2018,112:29-34. 5.Zhao,F.-J.;Jin,Y.;Liu,Z.-C.;Guo,C.;Li,T.-B.;Li,Z.-Y.;WangG.-G.*;Wu,Z.-L*.CrystalstructureanditerativesaturationmutagenesisofChKRED20forexpandedcatalyticscope.ApplMicrobiolBiotechnol.2017,101(23–24):8395–8404. 6.Guo,C.;Wu,Z.-L.*Constructionandfunctionalanalysisofawhole-cellbiocatalystbasedonCYP108N7.EnzymeandMicrobialTechnology,2017,106:28-34. 7.Liu,Y.-C.;Guo,C.;Liu,Y.;Wang,H.-B.;Wu,Z.-L.*Enzymaticcascadesforthestereo-complementaryepimerisationofinsitugeneratedepoxyalcohols.Org.Biomol.Chem.,2017,15,2562-2568. 8.Li,C.;Liu,Y.;Pei,X.-Q.;Wu,Z.-L.*Stereo-complementarybioreductionofsaturatedN-heterocyclicketones,ProcessBiochem.,2017,56,90-97. 9.Zhao,F.-J.;Liu,Y.;Pei,X.-Q.;Guo,C.;Wu,Z.-L.*SinglemutationsofketoreductaseChKRED20enhancethebioreductiveproductionof(1S)-2-chloro-1-(3,4-difluorophenyl)ethanol.ApplMicrobiolBiotechnol,2017,101(5):1945-1952. 10.Liu,Y.;Liu,Y.-C;Wu,Z.-L*.AsymmetricbioepoxidationcatalyzedwiththestyrenemonooxygenasefromPseudomonassp.LQ26.Bioresour.Bioprocess.2016,100(8):3567-3575. 11.Xu,G.-P.;Wang,H.-B.,Wu,Z.-L*.Efficientbioreductiveproductionof(S)-N-Boc-3-hydroxypiperidineusingketoreductaseChKRED03.ProcessBiochem.2016,51:881-885. 12.Pei,X.-Q.;Xu,M.-Y.;Wu,Z.-L.*Two“classical”OldYellowEnzymesfromChryseobacteriumsp.CA49:broadsubstratespecificityofChr-OYE1andlimitedactivityofChr-OYE2.J.Mol.Catal.B:Enzym.2016,123:91-99. 13.Zhao,F.-J.;Pei,X.-Q.;Ren,Z.-Q.;Wu,Z.-L.*Rapidasymmetricreductionofethyl4-chloro-3-oxobutanoateusingathermostabilizedmutantofketoreductaseChKRED20.ApplMicrobiolBiotechnol.2016.100(8):3567-3575. 14.Li,J.-J.;Pei,X.-Q.;Zhang,S.-B.;Wu,Z.-L*.ImprovingthethermostabilityofferuloylesterasebyDNAshufflingandsite-directedmutagenesis.ProcessBiochem.2015,50:1783-1787. 15.Li,J.-J.;Yi,Z.-L.;Pei,X.-Q.;Wu,Z.-L*.RemovalofthefreecysteineresiduereducesirreversiblethermalinactivationofFeruloylEsterase:evidencefromcirculardichroismandfluorescencespectra.ActaBiochimicaetBiophysicaSinica.2015,47(8):612-619. 16.Liu,Y.-C;Wu,Z.-L*.Switchableasymmetricbio-epoxidationofa,b-unsaturatedketones.Chem.Commun.2016,52(6),1158–1161. 17.Ren,Z.-Q;Liu,Y.;Pei,X.-Q;WangH.-B.;Wu,Z.-L*.Bioreductiveproductionofenantiopure(S)-duloxetineintermediatescatalyzedwithketoreductaseChKRED15.J.Mol.Catal.B:Enzym.2015,113,76–81. 18.Liu,Y.-C;Liu,Y.;Wu,Z.-L*.Synthesisofenantiopureglycidolderivativesviaaone-pottwo-stepenzymaticcascade.Org.Biomol.Chem.,2015,13,2146–2152 19.Xu,M.-Y.,Pei,X.-Q.,Wu,Z.-L.*Identificationandcharacterizationofanovel"thermophilic-like"OldYellowEnzymefromthegenomeofChryseobacteriumsp.CA49.J.Mol.Catal.B:Enzym.2014,108,64-71. 20.Tang,T.-X.;Liu,Y;Wu,Z.-L.*Characterizationofarobustanti-Prelogshort-chaindehydrogenase/reductaseChKRED20fromChryseobacteriumsp.CA49.J.Mol.Catal.B:Enzym.2014,105,82-88. 21.Liu,Y.,Tang,T.-X.,Pei,X.-Q.,Zhang,C.,Wu,Z.-L.*IdentificationofketonereductaseChKRED20fromthegenomeofChryseobacteriumsp.CA49forhighlyefficientanti-Prelogreductionof3,5-bis(trifluoromethyl)acetophenone.J.Mol.Catal.B:Enz.2014,102(4),1-8. 22.18.Wang,H.-B.,Pei,X.-Q.;Wu,Z.-L.*AnenoatereductaseAcrh-OYE4fromAchromobactersp.JA81:CharacterizationandapplicationinasymmetricbioreductionofC=Cbonds.Appl.Microbiol.Biotechnol.2014,98(2),705-715. 23.Yi,Z.-L.;Zhang,S.-B.*;Pei,X.-Q.;Wu,Z.-L.*Designofmutantsforenhancedthermostabilityofb-glycosidaseBglYfromThermusthermophilus.Bioresour.Technol.2013,129,629-633. 24.Lin,H.;Tang,D.-F.;Ahmed,A.A.Q.;Liu,Y.;Wu,Z.-L.*Mutationsattheputativeactivecavityofstyrenemonooxygenase:enhancedactivityandreversedenantioselectivity.J.Biotechnol.2012,161,235-241. 25.Zhang,S.-B.;Pei,X.-Q.;Wu,Z.-L.*MultipleaminoacidsubstitutionssignificantlyimprovethethermostabilityofferuloylesteraseAfromAspergillusniger.Bioresour.Technol.2012,117,140-147. 26.Liu,Y.-J.;Pei,X.-Q.;Lin,H.;Gai,P.;Liu,Y.-C.;Wu,Z.-L.*AsymmetricbioreductionofactivatedalkenesbyanovelisolateofAchromobacterspeciesproducingenoatereductase.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.*Apracticalhigh-throughputscreeningsystemforferuloylesterases:substratedesignandevaluation.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.*Biocatalysisasanalternativefortheproductionofchiralepoxides:acomparativereview.J.Mol.Catal.B:Enzym.2011,72(3-4),77-89.(Invitedreview) 29.Tang,C.-G.;Lin,H.;Zhang,C.;Liu,Z.-Q.;Yang,T.;Wu,Z.-L.*HighlyenantioselectivebioreductionofN-methyl-3-oxo-3-(thiophen-2-yl)propanamidefortheproductionof(S)-duloxetine.Biotechnol.Lett.2011,33(7),1435-1440. 30.Lin,H.;Liu,Y.;Wu,Z.-L.*Highlydiastereo-andenantio-selectiveepoxidationofsecondaryallylicalcoholscatalyzedbystyrenemonooxygenase.Chem.Commun.,2011,47,2610-2612. 31.Lin,H.;Liu,Y.;Wu,Z.-L.*AsymmetricepoxidationofstyrenederivativesbystyrenemonooxygenasefromPseudomonassp.LQ26:effectsofa-andb-substituents.Tetrahedron:Asymmetry,2011,22,134-137. 32.Yi,Z.-L.;Pei,X.-Q.;Wu,Z.-L.*IntroductionofglycineandprolineresiduesontoproteinsurfaceincreasesthethermostabilityofendoglucanaseCelAfromClostridiumthermocellum.Bioresour.Technol.2011,102(3),3636–3638 33.Pei,X.-Q.;Yi,Z.-L.;Tang,C.-G.;Wu,Z.-L.*Threeaminoacidchangescontributemarkedlytothethermostabilityofb-glucosidaseBglCfromThermobifidafusca.Bioresour.Technol.2011,102(3),3337–3342. 34.Qaed,A.A.;Lin,H.;Tang,D.-F.;Wu,Z.-L.*Rationaldesignofstyrenemonooxygenasemutantswithalteredsubstratepreference.Biotechnol.Lett.2011,33,611-616. 35.Zhang,S.-B.;Wu,Z.-L.*IdentificationofaminoacidresiduesresponsibleforincreasedthermostabilityofferuloylesteraseAfromAspergillusnigerusingthePoPMuSiCalgorithm.Bioresour.Technol.2011,102(2),2093–2096. 36.Lin,H.;Qiao,J.;Liu,Y.;Wu,Z.-L.*StyrenemonooxygenasefromPseudomonassp.LQ26catalyzestheasymmetricepoxidationofbothconjugatedandunconjugatedalkenes.J.Mol.Catal.B:Enzym.2010,67(3-4),236-241. 37.Zhang,Z.-G.;Yi,Z.-L.;Pei,X.-Q.;Wu,Z.-L.*ImprovingthethermostabilityofGeobacillusstearothermophilusxylanaseXT6bydirectedevolutionandsite-directedmutagenesis.Bioresour.Technol.2010,101(23),9272-9278. 38.Yi,Z.-L.;Wu,Z.-L.*Mutationsfromafamily-shuffling-libraryrevealaminoacidresiduesresponsibleforthethermostabilityofendoglucanaseCelAfromClostridiumthermocellumBiotechnol.Lett.2010,32(12),1869-1875. 39.Tang,Z.,Salamanca-Pinzon,S.G.,Wu,Z.L.,Xiao,Y.,Guengerich,F.P.,HumancytochromeP4504F11:Heterologousexpressioninbacteria,purification,andcharacterizationofcatalyticfunction.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.EnhancedbacterialexpressionofseveralmammaliancytochromeP450sbycodonoptimizationandchaperonecoexpression.Biotechnol.Lett.2009,31(10),1589-1593. 41.Zhang,Z.-G.;Liu,Y.;Guengerich,F.P.;Matse,J.H.;ChenJ.;Wu,Z.-L.*Identificationofaminoacidresiduesinvolvedin4-chloroindole3-hydroxylationbycytochromeP4502A6usingscreeningofrandomlibraries.J.Biotechnol.2009,139(1),12-18.

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