基本信息
刘文  男  博导  中国科学院上海有机化学研究所
电子邮件: wliu@mail.sioc.ac.cn
通信地址: 上海市零陵路345号
邮政编码: 200032

招生信息

   
招生专业
070303-有机化学
100705-微生物与生化药学
招生方向
复杂天然产物的生物合成(遗传学、生物化学和化学)研究
以产量提高和结构多样性为目的组合生物合成研究
以基因组扫描为手段的新型天然产物发现研究

教育背景

1998-01--2000-07   美国加州大学戴维斯分校化学系   联合培养研究生
1994-09--2000-07   中国医学科学院(北京协和医科大学)   硕士、博士学位
1988-09--1992-07   四川大学   学士学位

工作经历

   
工作简历
2010-08~现在, 中国科学院湖州生物制造创新中心, 中心主任
2003-08~现在, 中科院上海有机化学研究所, 研究员
2001-09~2003-08,美国威斯康星大学麦迪逊分校药学院, 研究助理
2000-09~2001-08,美国加州大学戴维斯分校化学系, 博士后
1998-01~2000-07,美国加州大学戴维斯分校化学系, 联合培养研究生
1994-09~2000-07,中国医学科学院(北京协和医科大学), 硕士、博士学位
1988-09~1992-07,四川大学, 学士学位

教授课程

生物有机化学

专利与奖励

   
奖励信息
(1) 第八届谈家桢生命科学创新奖, 专项, 2015
(2) 国家百千万人才工程“有突出贡献中青年专家”, 国家级, 2015
(3) 上海市优秀学术带头人, , 市地级, 2013
(4) The Distinguished Lectureship Award(日本化学会), , 其他, 2013
(5) 上海市领军人才, , 省级, 2012
(6) 中科院研究生优秀指导教师奖, , 院级, 2012
(7) 中国科学院优秀导师奖, , 院级, 2011
(8) 明治乳业生命科学奖(优秀奖), , 部委级, 2010
(9) 中国科学院“****”终期评估优秀, , 院级, 2010
(10) 中国药学会-赛诺菲安万特青年生, , 部委级, 2010
(11) 国务院特殊津贴, , 国家级, 2010
(12) 现代生物技术集成的红霉素发酵生, 一等奖, 省级, 2008
专利成果
( 1 ) 诺丝七肽的生物合成基因簇, 2011, 第 1 作者, 专利号: ZL 2009 1 0053427.7
( 2 ) NOVEL GENE CLUSTER, 2010, 第 1 作者, 专利号: PCT/CN2009/074178
( 3 ) 一种提高红霉素产量的方法, 2010, 第 1 作者, 专利号: 201010154463.5
( 4 ) ΦC31介导的基因重组并应用于红霉素产生菌种的遗传改造, 2012, 第 1 作者, 专利号: ZL 2009 1 0194419.4
( 5 ) 诺卡噻唑菌素的生物合成基因簇及其应用, 2013, 第 1 作者, 专利号: ZL 2010 1 0240885.4
( 6 ) 一种萨菲菌素的生物合成基因簇, 2013, 第 1 作者, 专利号: 2ZL 2009 1 0168784.8
( 7 ) 替曲卡星A的生物合成基因簇及其应用, 2012, 第 1 作者, 专利号: ZL 2008 1 0036248.8
( 8 ) 诺卡噻唑菌素的生物合成基因簇及其应用, 2010, 第 1 作者, 专利号: PCT/CN2010/075442
( 9 ) 氯丝菌素的生物合成基因簇及应用, 2009, 第 1 作者, 专利号: ZL 2005 1 0027456.8
( 10 ) 阿嗪霉素的生物合成基因簇, 2010, 第 1 作者, 专利号: ZL 2008 1 003478.8
( 11 ) 一种重组质粒、构建方法和用于红霉素产生菌的遗传改造, 2010, 第 1 作者, 专利号: ZL 2007 1 0173704.9
( 12 ) 新型硫链丝菌素类似物及其制法和用途, 2014, 第 1 作者, 专利号: ZL 2011 1 0022499.2
( 13 ) 氟代诺斯菌素及其制法和用途, 2013, 第 1 作者, 专利号: ZL 2010 1 0519796.3
( 14 ) 基因工程改造六-甲基水杨酸合成酶并组合生物合成螺环乙酰乙酸内酯类抗生素, 2012, 第 1 作者, 专利号: ZL 2009 1 0247567.8
( 15 ) 一种优化红霉素发酵组分的菌种、构建方法和用途, 2012, 第 1 作者, 专利号: ZL 2007 1 0173703.4
( 16 ) 一种构建基因工程FK506高产菌株的方法和筑波链霉菌高产菌株, 2011, 第 1 作者, 专利号: 201110318990.X
( 17 ) 一种短链脱氢酶TsrU的功能及其应用, 2016, 第 1 作者, 专利号: ZL 2012 1 0010297.0
( 18 ) 番红霉素的生物合成基因簇, 2012, 第 2 作者, 专利号: ZL 2007 1 0037087.X
( 19 ) 一株淡黄色链霉菌突变菌株、构建方法及其用途, 2013, 第 1 作者, 专利号: ZL 2011 1 0197033.6
( 20 ) 林可霉素生物合成中间产物及其制法和用途, 2014, 第 1 作者, 专利号: 201410625571.4
( 21 ) 新型硫链丝菌素类似物及其制法和用途, 2014, 第 1 作者, 专利号: 201410216093.1
( 22 ) 抗霉素类似物及其制备方法和用途, 2013, 第 1 作者, 专利号: 201310380322.9

出版信息

   
发表论文
(1) NosP-Regulated Nosiheptide Production Responds to Both Peptidyl and Small-Molecule Ligands Derived from the Precursor Peptide, Cell chemical biology, 2018, 通讯作者
(2) Isolation, structure elucidation, and biosynthesis of a cysteate-containing nonribosomal peptide in Streptomyces lincolnensis, Journal of Organic Chemistry, 2018, 通讯作者
(3) Structural insights into a flavin-dependent [4+2] cyclase that catalyzes trans-decalin formation in pyrroindomycin biosynthesis, Cell chemical biology, 2018, 通讯作者
(4) Biosynthesis of lincosamide antibiotics: reactions associated with degradation and detoxification pathways play a constructive role, Accounts of Chemical Research, 2018, 通讯作者
(5) A linear hydroxymethyl tetramate undergoes an acetylation–elimination process for exocyclic methylene formation in the biosynthetic pathway of pyrroindomycins, Organic & Biomolecular Chemistry, 2017, 通讯作者
(6) Chemo-enzymatic Synthesis of Equisetin, Chemical Communications, 2017, 通讯作者
(7) Post-translational modifications involved in the biosynthesis of thiopeptide antibiotics, Organic & Biomolecular Chemistry, 2017, 通讯作者
(8) Characterization of the Metallo-dependent Amidohydrolases Responsible for "auxiliary" Leucinyl Removal in the Biosynthesis of 2,2'-bipyridine Antibiotics, Synthetic and Systems Biotechnology, 2017, 通讯作者
(9) Enzymatic Competition and Cooperation Branch the Caerulomycin Biosynthetic Pathway toward Different 2,2'-bipyridine members, Organic & Biomolecular Chemistry, 2017, 通讯作者
(10) Bio-inspired Engineering of Thiopeptide Antibiotics advances the Expansion of Molecular Diversity and Utility, Current Opinion in Biotechnology, 2017, 通讯作者
(11) Biosynthesis and molecular engineering of templated natural products, National Science Review,, 2017, 通讯作者
(12) 4-Alkyl-L-(dehydro)proline biosynthesis in Actinobacteria involves N-terminal nucleophile-hydrolase activity of -glutamyltranspeptidase homolog for C-C bond cleavage, Nature Communications, 2017, 通讯作者
(13) Processing 2-Methyl-l-Tryptophan through Tandem Transamination and Selective Oxygenation Initiates Indole Ring Expansion in the Biosynthesis of Thiostrepton, Journal of the American Chemical Society, 2017, 通讯作者
(14) Thiolation Protein-Based Transfer of Indolyl to a Ribosomally Synthesized Polythiazolyl Peptide Intermediate during the Biosynthesis of the Side Ring System of Nosiheptide, Journal of the American Chemical Society, 2017, 通讯作者
(15) Coordinative modulation of chlorothricin biosynthesis by binding of the glycosylated intermediates and end product to a responsive regulator ChlF1, Journal of Biological Chemistry, 2016, 通讯作者
(16) Biosynthesis-based artificial evolution of natural products, SCIENCE CHINA Chemistry, 2016, 通讯作者
(17) Enzymatic [4+2] Cycloadditions in the Biosynthesis of Spirotetramates and Spirotetronates, Methods in Enzymology, 2016, 通讯作者
(18) Molecular engineering of thiostrepton via single “base”-based mutagenesis to generate side ring-derived variants, Organic Chemistry Frontiers, 2016, 通讯作者
(19) Precursor-Directed Mutational Biosynthesis Facilitates the Functional Assignment of Two Cytochromes P450 in Thiostrepton Biosynthesis, ACS Chemical Biology, 2016, 通讯作者
(20) Differences in PLP-Dependent Cysteinyl Processing Lead to Diverse S‑Functionalization of Lincosamide Antibiotics, Journal of the American Chemical Society, 2016, 通讯作者
(21) An α/β-hydrolase fold enzyme with a dual activity for endopeptidyl hydrolysis and epoxide ring-opening/ macrocyclization in thiostrepton biosynthesis, Proceedings of the National Academy of Sciences of the United States of America, 2016, 通讯作者
(22) Cyclization of polyketides and non-ribosomal peptides on and off their assembly lines, Natural Product Reports, 2016, 通讯作者
(23) Recent advances in understanding the enzymatic reactions of [4+2] cycloaddition and spiroketalization, Current Opinion in Chemical Biology, 2016, 通讯作者
(24) Enzyme-Dependent [4 + 2] Cycloaddition Depends on Lid-like Interaction of the N-Terminal Sequence with the Catalytic Core in PyrI4, Cell Chemical Biology, 2016, 通讯作者
(25) Concurrent modifications of the C-terminus and side ring of thiostrepton and their synergistic effects with respect to improving antibacterial activities, Organic Chemistry Frontiers, 2016, 通讯作者
(26) Metabolic coupling of two small-molecule thiols programs the biosynthesis of lincomycin A, Nature, 2015, 通讯作者
(27) An enzymatic [4+2] cyclization cascade creates the pentacyclic core of pyrroindomycins, Nature Chemical Biology, 2015, 通讯作者
(28) Thiopeptide Antibiotics Exhibit a Dual Mode of Action against Intracellular Pathogens by Affecting Both Host and Microbe, Chemistry& Biology, 2015, 通讯作者
(29) The versatile low-molecular-weight thiols: Beyond cell protection, Bioessays, 2015, 通讯作者
(30) 1,19-seco-Avermectin Analogues from a ΔaveCDE Mutant Streptomyces avermectinius Strain, Journal of Natural Products, 2015, 通讯作者
(31) Target-Oriented Design and Biosynthesis of Thiostrepton-Derived Thiopeptide Antibiotics with Improved Pharmaceutical Properties, Organic Chemistry Frontiers, 2015, 通讯作者
(32) Structure-based Mechanistic Insights into Terminal Amide Synthase in Nosiheptide-Represented Thiopeptides Biosynthesis, Scientific Reports, 2015, 通讯作者
(33) Insight into bicyclic thiopeptide benefited from development of a uniform approach for molecular engineering and production improvement, Chemical Science , 2014, 通讯作者
(34) Effect of Stereochemistry of Avermectin-Like 6,6-Spiroketals on Biological Activities and Endogenous Biotransformations in Streptomyces avermectinius, ChemBioChem , 2014, 通讯作者
(35) Discovery and efficient synthesis of a biologically active alkaloid inspired by thiostrepton biosynthesis, Tetrahedron, 2014, 通讯作者
(36) Multiplexing of Combinatorial Chemistry in Antimycin Biosynthesis: Expansion of Molecular Diversity and Utility, Angewandte Chemie International Edition, 2013, 通讯作者
(37) Opportunities and challenges from current investigations into the biosynthetic logic of nosiheptide-represented thiopeptide antibiotics, Current Opinion in Chemical Biology , 2013, 通讯作者
(38) Biosynthesis of thiopeptide antibiotics and their pathway engineering, Natural Product Reports, 2013, 通讯作者
(39) Spiroketal formation and modification in avermectin biosynthesis involves a dual activity of AveC, Journal of the American Chemical Society, 2013, 通讯作者
(40) Characterization of a key aminoglycoside phosphotransferase in gentamicin biosynthesis, Bioorganic and Medicinal Chemistry Letters, 2013, 通讯作者
(41) FK506 maturation involves a cytochrome P450 protein-catalyzed four electron oxidation in parallel with C-31 O-methylation, Journal of Bacteriology, 2013, 通讯作者
(42) Aromatic polyketides produced by bacterial iterative type I polyketide synthases, ACS Catalysis, 2013, 通讯作者
(43) ThioFinder: a web-based tools for the identification of thiopeptide gene clusters in DNA sequence, PloS One, 2012, 通讯作者
(44) Biosynthetic pathway for high structural diversity of a common dilactone core in antimycin production, Organic Letter , 2012, 通讯作者
(45) Improvement of FK506 production in Streptomyces tsukubaensis by genetic enhancement of the supply of unusual polyketide extender untis via utilization of two distinct site-specific recombination systems, Applied and Environmental Microbiology , 2012, 通讯作者
(46) Radical-mediated enzymatic methylation: a tale of two SAMS, Accounts of Chemical Research, 2012, 通讯作者
(47) Caerulomycins and collismycins share a common paradigm for 2,2’-bipyridine biosynthesis via an unusual hybrid polyketide-peptide assembly logic, of the American Chemical Society , 2012, 通讯作者
(48)  Insights into quinaldic acid formation in thiostrepton biosynthesis facilitating fluorinated thiopeptide generation, Chem. Biol. , 2012, 通讯作者
(49) Insights into pyrroindomycin biosynthesis reveal a uniform paradigm for tetromate/tetronate formation, Journal of the American Chemical Society , 2012, 通讯作者
(50) Complex biotransformations catalyzed by radical S-adenosylmethionine enzymes, Journal of Biological Chemistry , 2011, 通讯作者
(51) An artificial attB site for specific recombination facilitates genetic manipulations towards improving the erythromycin A production in an industrial Saccharopolyspora erythraea strain, Applied and Environmental Microbiology , 2011, 通讯作者
(52) Transcriptome mining of active biosynthetic pathways and their associated products in Streptomyces flaveolus, Angewandte Chemie International Edition , 2011, 通讯作者
(53) Radical-mediated enzymatic carbon chain fragmentation-recombination, Nat. Chem. Biol. , 2011, 通讯作者
(54) Characterization of NocL involved in thiopeptide nocarthiacin I biosynthesis,  J. Biol. Chem. , 2011, 通讯作者
(55) Thiostrepton maturation involving a deesterification-amidation way to process the C-terminally methylated peptide backbone,  J. Am. Chem. Soc. , 2011, 通讯作者
(56) Cloning, sequencing and characterization of the biosynthetic gene cluster of sanglifehrin A, a potent cyclophilin inhibitor, Mol. BioSyst. , 2011, 通讯作者
(57) Knocking out of tailoring genes eryK and eryG in an industrial erythromycin-producing strain of Saccharopolyspora erythraea leading to overproduction of erythromycin B, C and D at different conversion ratios, Letters in Applied Microbiology , 2011, 通讯作者
(58) NosA catalyzing carboxyl-terminal amide formation in nosiheptide maturation via an enamine dealkylation on the serine-extended precursor peptide, J. Am. Chem. Soc. , 2010, 通讯作者
(59) Knocking out of tailoring genes eryK and eryG in an industrial erythromycin-producing strain of Saccaropolyspora erythraea leading to overproduction of erythromycin B, C and D at different conversion ratios, Lett. Appl. Microbiol., 2010, 通讯作者
(60) Moving posttranslational modifications forward to biosynthesize the glycosylated antibiotic nocathiacin I in Nocardia sp. ATCC202099, Mol. BioSyst., 2010, 通讯作者
(61) Insights into bacterial 6-methylsalicylic acid synthase and its engineering to orsellinic acid synthase for new spirotetronate generation, Chem. Biol., 2010, 通讯作者
(62) Biosynthesis of 3-methoxy-5-methyl naphthoic acid and its incorporation into the antitumor antibiotic azinomycin B, Mol. Biosyst. , 2010, 通讯作者
(63) Nosiheptide biosynthesis featuring a unique indole side ring formation on the characteristic thiopeptide framework, ACS Chem. Biol., 2009, 通讯作者
(64) Thiopeptide biosynthesis featuring ribosomally synthesized precursor peptides and conserved posttranslational modifications, Chem. Biol. , 2009, 通讯作者
(65) Dissection of two transfer reactions centered on acyl-S-carrier protein intermediates for incorporating 5-chloro-6-methyl-O-methylsalicyclic acid into chlorothricin, ChemBioChem, 2008, 通讯作者
(66) Characterization of the azinomycin B biosynthetic gene cluster revealing a different iterative type I polyketide synthase for naphthoate biosynthesis, Chem. Biol., 2008, 通讯作者
(67) Cloning and characterization of the tetrocarcin A gene cluster from Micromonospora chalcea NRRL 11289 reveals a highly conserved stratety fro tetronate biosynthesis in spirotetronate antibiotics, J. Bacteriol., 2008, 通讯作者
(68) Genetic modulation of the overexpression of tailoring genes eryK and eryG leading to the improvement of erythromycin A purity and production in fermentation of Saccharopolyspora erythraea, Appl. Environ. Microbiol. , 2008, 通讯作者
(69) Characterization of the saframycin A gene cluster from Streptomyces lavendulae NRRL 11002 revealing a NRPS system for assembling the unusual tetrapeptidyl skeleton in an iterative manner, J. Bacteriol. , 2008, 通讯作者
(70) In vivo manipulation of the bleomycin biosynthetic gene cluster in Streptomyces verticillus ATCC15003 revealing new insights into its biosynthetic pathway, J. Biol. Chem., 2008, 通讯作者
(71) A self-phosphopantetheinylating polyketide synthase producing a linear polyene to initiate the biosynthesis of the enediyne antitumor antibiotics, Proc. Natl. Acad. Sci. U.S.A., 2008, 第 4 作者
(72) Characterization of the maduropeptin biosynthetic gene cluster from Actinomadura madurae ATCC 39144 supporting a unifying paradigm for enediyne biosynthesis, J. Am. Chem. Soc. , 2007, 第 3 作者
(73) Single chemical modifications of the enediyne core of C-1027, a radiomimetic antitumor drug, result in markedly varied cellular responses to DNA double strand breaks, Cancer Res., 2007, 第 4 作者
(74) Cloning and characterization of a bacterial iterative type I polyketide synthase gene encoding the 6-methylsalicyclic acid synthase, Biochem. Biophys. Res. Commun. , 2006, 通讯作者
(75) Cloning, sequencing and genetic characterization of the Chlorothricin gene cluster from Streptomyces antibioticus DSM 40725 as a model for spirotetronate antibiotic biosynthesis, Chem. Biol. , 2006, 通讯作者
(76) Biosynthesis of the b-amino acid moiety of the enediyne antitumor antibiotic C-1027 featuring b-amino acyl-S-carrier protein intermediates, J. Am. Chem. Soc. , 2005, 第 4 作者
(77) The neocarzinostatin biosynthesis gene cluster from Streptomyces carzinostaticus ATCC15944 involved two iterative type I polyketide synthase, Chem. Biol. , 2005, 第 1 作者
(78) Biochemical characterization of the SgcA1 ?-D-glucopyranosyl-1-phosphate thymidyltransferase from the enediyne antitumor antibiotic C-1027 biosynthetic pathway and overexpression of sgcA1 in Streptomyces globisporus to improve C-1027 production, J. Natl. Prod. , 2004, 第 2 作者
(79) A novel dehydroalanine-dependent tyrosine aminomutase in enediyne antitumor antibiotic C-1027 biosynthesis, J. Am. Chem. Soc., 2003, 第 2 作者
(80) Discovering and Expressing Cryptic Metabolic Pathways: Enediyne Natural Products as a Paradigm, Nat. Biotechnol. , 2003, 第 4 作者
(81) Rapid PCR Amplification of Minimal Enediyne PKS Cassettes Leads to a Predictive Familial Classification Model For Divergent Enediyne PKS Genes, Proc. Natl. Acad. Sci. U.S.A., 2003, 第 1 作者
(82) Biosynthesis of Enediyne Antitumor Antibiotic C-1027, Science , 2002, 第 1 作者
(83) Genes for Production of Enediyne Antitumor Antibiotic C-1027 in Streptomyces globisporus are Clustered with the cagA Gene that Encodes the C-1027 Apoprotein, Antimicrob. Agent. Chemother., 2000, 第 1 作者

科研活动

   
科研项目
( 1 ) 新型聚酮和聚肽类抗生素的次生代谢(生物合成)研究, 主持, 国家级, 2009-01--2012-12
( 2 ) 具有重要生理活性的天然产物的化学合成, 参与, 国家级, 2009-09--2014-08
( 3 ) 以产量提高、品质优化为导向的重要抗生素工业用生产菌株的代谢工程改造研究, 主持, 国家级, 2011-02--2013-12
( 4 ) 以生物合成机制解析为基础的抗生素结构改造和品质优化研究, 主持, 省级, 2013-07--2015-06
( 5 ) 化学理念指导的抗生素生产菌种遗传改造关键技术研究与应用, 主持, 部委级, 2013-01--2015-06
( 6 ) 化学小分子探针引导的细胞信号转导途径研究, 参与, 国家级, 2013-01--2015-12
( 7 ) 基于生物合成机制研究的林可霉素工业生产菌株的代谢工程改造项目支出计划, 主持, 研究所(学校), 2012-01--2014-12
( 8 ) 天然产物独特结构单元的生物合成机制研究, 主持, 国家级, 2009-01--2012-12
( 9 ) 以活性(抗肿瘤和抗感染)与作用机制研究为导向的硫肽类抗生素的生物合成, 主持, 国家级, 2015-01--2019-12
( 10 ) 联二吡啶类抗生素核心骨架的生物合成机制的比较研究, 主持, 国家级, 2015-01--2018-12
( 11 ) 以多样性为导向的天然产物生物合成研究, 主持, 国家级, 2016-01--2020-12
( 12 ) 硫肽非天然氨基酸衍生探针的生物合成及应用研究, 主持, 国家级, 2015-01--2015-12
( 13 ) 化学理念指导的抗生素生产菌种遗传改造关键技术研究与应用, 主持, 部委级, 2013-01--2016-12
( 14 ) 肽类天然药物的合成生物学研究, 主持, 省级, 2014-09--2017-08
参与会议
(1)Diversity-Oriented Biosynthesis of Natural Products   2015-11-10
(2)Diversity-oriented biosynthesis of natural products: Chemical and biological basis for expansion of molecular utility    2015-03-24
(3)以生化反应为基础的新生物合成途径及其相关天然产物的发现研究   第十三届全国均相催化学术会议   2013-11-01
(4)以多样性为导向的天然产物生物合成研究   第八届全国有机化学研讨会   2013-10-01
(5)Biosynthesis-Based Mining of New Pathways Their Associated Natural Products   英国John Innes Centre-中国科学院   Wen Liu   2013-04-13
(6)Combinatorial Mining of New Biosynthetic Pathways Their Associated Natural Products   日本药学会第133届年会   Wen Liu   2013-03-23
(7)Biosynthetic Mining of New Pathways Their Associated Natural Products:   日本化学会第93届年会   Wen Liu   2013-03-09
(8)Generality and Specificity in Thiopeptide Biosynthesis   第十六届国际放线菌生物学大会会议(ISBA16)   Wen Liu   2011-12-11
(9) Thiopeptide Antibiotic Biosynthesis: Generality and Specificity   2011年天然产物生物合成学术研讨会   Wen Liu   2011-09-16