研究员
刘文
职  称: 研究员
学  历: 博士研究生
电  话: 86-21-54925111
职  务: 课题组长
传  真: 86-21-64166128
电子邮件: wliu@mail.sioc.ac.cn
个人网页:
通信地址: 上海市零陵路345号
个人简历

1988年9月-1992年7月,四川大学生物工程系微生物专业,学士学位;

1994年9月---1997年7月,中国协和医科大学(中国医学科学院),硕士学位;

1997年9月---2000年7月;中国协和医科大学(中国医学科学院)博士学位(美国加州大学戴维斯分校化学系联合培养);

2000年9月---2001年8月,美国加州大学戴维斯分校化学系(DepartmentofChemistry,UniversityofCalifornia-Davis),博士后;

2001年9月---2003年8月,美国威斯康星大学麦迪逊分校药学院(School of Pharmacy,University of Wisconsin-Madison),研究助理;

2003年8月-至今,中国科学院上海有机化学研究所,研究员。

研究方向

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

以基因组挖掘为手段的新型天然产物发现研究

社会任职
获奖及荣誉

2019年 上海市自然科学奖一等奖(单位排名第一、个人排名第一)

2015年 谈家桢生命科学奖创新奖

2013年 日本化学会The Distinguished Lectureship Award

2010年 明知乳业生命科学奖优秀奖

2008年 上海市科技进步奖一等奖(单位排名第三、个人排名第五)

代表论著

1.       Botao Cheng#, Jiwu Huang#, Yuting Duan, Wen Liu*. Association of radical chemistry with LanD flavoprotein activity for C-terminal macrocyclization of a ribosomal peptide through the formation of an unsaturated thioether residue. Angewandte Chemie-International Edition 2023, 62(35), e202308733.

2.       Zhijun Tang#, Bo Pang#, Chang Liu#, Shengjie Guo, Xudong Qu, Wen Liu*. Formation and loading of a (2S)-2-ethylmalonamyl starter unit in the assembly line of polyketide-nonribosomal peptide hybrid sanglifehrin A. Angewandte Chemie-International Edition 2023, 62(23), e202217090.

3.       Hongbo Wang#, Yike Zou#, Miao Li#, Zhijun Tang#, Jiabao Wang, Zhenhua Tian, Nina Strassner, Qian Yang, Qingfei Zheng, Yujiao Guo, Wen Liu*, Lifeng Pan*, K. N. Houk*. A cyclase that catalyses competing 2 + 2 and 4 + 2 cycloadditions. Nature Chemistry 2023, 15(2), 177-184.

4.       Yiyuan Cheng, Xuan Yi, Yan Zhang, Qingli He, Dandan Chen, Weiguo Cao, Pengfei Fang*, Wen Liu*. Oxidase heterotetramer completes 1azabicyclo[3.1.0]hexane formation with the association of a nonribosomal peptide synthetase. Journal of the American Chemical Society 2023, 145(16), 8896-8907.

5.       Yanqing Xue#, Xiaofeng Wang#, Wen Liu*. Reconstitution of the linaridin pathway provides access to the family-determining activity of two membrane-associated proteins in the formation of structurally underestimated cypemycin. Journal of the American Chemical Society 2023, 145(12), 7040-7047.

6.       Shengjie Guo, Yueqian Sang, Chao Zheng, Xiao-Song Xue, Zhijun Tang*, Wen Liu*. Enzymatic αketothioester decarbonylation occurs in the assembly line of barbamide for skeleton editing. Journal of the American Chemical Society 2023, 145(9), 5017-5028.

7.       Ling Hu, Yi Qiao, Jingyu Liu, Chao Zheng, Xiaofeng Wang, Peng Sun, Yucheng Gu, Wen Liu*. Characterization of histidine functionalization and its timing in the biosynthesis of ribosomally synthesized and posttranslationally modified thioamitides. Journal of the American Chemical Society 2022, 144(10), 4431-4438.

8.       Bo Li, Xingyi Guan, Song Yang, Yike Zou, Wen Liu*, K. N. Houk*. Mechanism of the stereoselective catalysis of DielsAlderase PyrE3 involved in pyrroindomycin biosynthesis. Journal of the American Chemical Society 2022, 144(11), 5099-5107.

9.       Sili Wang, Yiyuan Cheng, Xiaofeng Wang, Qian Yang, Wen Liu*. Tracing of acyl carrier protein-channeled mitomycin intermediates in Streptomyces caespitosus facilitates characterization of the biosynthetic steps for AHBAGlcN formation and processing. Journal of the American Chemical Society 2022, 144(33), 14945-14956.

10.    Zhi Lin#, Yufeng Xue#, Xiao-Wei Liang, Jian Wang, Shuangjun Lin, Jiang Tao, Shu-Li You*, Wen Liu*. Oxidative indole dearomatization for asymmetric furoindoline synthesis by a flavin-dependent monooxygenase involved in the biosynthesis of bicyclic thiopeptide thiostrepton. Angewandte Chemie-International Edition 2021, 60(15), 8401-8405.

11.    Bo Pang#, Rijing Liao#, Zhijun Tang#, Shengjie Guo, Zhuhua Wu, Wen Liu*. Caerulomycin and collismycin antibiotics share a trans-acting flavoprotein-dependent assembly line for 2,2'-bipyridine formation. Nature Communications 2021, 12, 3124.

12.    Botao Cheng#, Heng Guo#, Haoyang Wang, Qunfei Zhao, Wen Liu*. Dissection of the enzymatic process for forming a central imidazopiperidine heterocycle in the biosynthesis of a series c thiopeptide antibiotic. Journal of the American Chemical Society 2021, 143(34), 13790-13797.

13.    Zhijun Tang#; Haoyu Tang#, Wanqiu Wang#, Yufeng Xue, Dandan Chen, Weihua Tang*, Wen Liu*. Biosynthesis of a new fusaoctaxin virulence factor in Fusarium graminearum relies on a distinct path to form a guanidinoacetyl starter unit priming nonribosomal octapeptidyl assembly. Journal of the American Chemical Society 2021, 143(47), 19719-19730.

14.    Yanping Qiu#, Jingyu Liu#, Yuping Li, Yanqing Xue, Wen Liu*. Formation of an aminovinyl-cysteine residue in thioviridamides occurs through a path independent of known lanthionine synthetase activity. Cell Chemical Biology 2021, 28(5), 675-685.

15.    Yanan Du#, Yanping Qu#, Xiang Meng, Junyin Feng, Jiang Tao, Wen Liu*. A heterotrimeric dehydrogenase complex functions with 2 distinct YcaO proteins to install 5 azole heterocycles into 35-membered sulfomycin thiopeptides. Journal of the American Chemical Society 2020, 142(18), 8454-8463.

16.    Yike Zou, Song Yang, Jacob N. Sanders, Wei Li, Peiyuan Yu, Hongbo Wang, Zhijun Tang, Wen Liu*, K. N. Houk*. Computational investigation of the mechanism of Diels-Alderase PyrI4. Journal of the American Chemical Society 2020, 142(47), 20232-20239.

17.    Daozhong Zhang, Fang Zhang, Wen Liu*. A KAS-III heterodimer in lipstatin biosynthesis nondecarboxylatively condenses C8 and C14 fatty acyl-CoA substrates by a variable mechanism during the establishment of a C22 aliphatic skeleton. Journal of the American Chemical Society 2019, 141(9), 3993-4001.

18.    Daozhong Zhang, Zhijun Tang, Wen Liu*. Biosynthesis of lincosamide antibiotics: reactions associated with degradation and detoxification pathways play a constructive role. Accounts of Chemical Research 2018, 51(6), 1496-1506.

19.    Qingfei Zheng#, Yukang Gong#, Yujiao Guo, Zhixiong Zhao, Zhuhua Wu, Zixuan Zhou, Dandan Chen, Lifeng Pan*, Wen Liu*. Structural insights into a flavin-dependent [4+2] cyclase that catalyzes trans-decalin formation in pyrroindomycin biosynthesis. Cell Chemical Biology 2018, 25(6), 718-727.

20.    Jingjing Li, Yue Li, Guoqing Niu, Heng Guo, Yanping Qiu, Zhi Lin, Wen Liu*, Huarong Tan*. NosP-regulated nosiheptide production responds to both peptidyl and small-molecule ligands derived from the precursor peptide. Cell Chemical Biology 2018, 25(2), 143-153.

21.    Guannan Zhong, Qunfei Zhao, Qinling Zhang, Wen Liu*. 4-Alkyl-L-(dehydro)proline biosynthesis in actinobacteria involves N-terminal nucleophile-hydrolase activity of γ-glutamyltranspeptidase homolog for C-C bond cleavage. Nature Communications 2017, 8, 16109.

22.     Zhi Lin, Jia Ji, Shuaixiang Zhou, Fang Zhang, Jiequn Wu, Yinlong Guo, Wen Liu*. 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, 139(35), 12105-12108.

23.     Yanping Qiu#, Yanan Du#, Fang Zhang, Rijing Liao, Shuaixiang Zhou, Chao Peng, Yinlong Guo, Wen Liu*. 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, 139(50), 18186-18189.

24.     Zhi Lin, Qingli He, Wen Liu*. Bio-inspired engineering of thiopeptide antibiotics advances the expansion of molecular diversity and utility. Current Opinion in Biotechnology 2017, 48, 210-219.

25.     Qingfei Zheng#, Shoufeng Wang#, Panpan Duan, Rijing Liao, Dandan Chen, Wen Liu*. An α/β-hydrolase fold protein in the biosynthesis of thiostrepton exhibits a dual activity for endopeptidyl hydrolysis and epoxide ring opening/macrocyclization. Proceedings of the National Academy of Sciences of the United States of America 2016, 113(50), 14318-14323.

26.     Bo Pang#, Min Wang#, Wen Liu*. Cyclization of polyketides and non-ribosomal peptides on and off their assembly lines. Natural Product Reports 2016, 33(2), 162-173.

27.     Qingfei Zheng#, Yujiao Guo#, Linlin Yang, Zhixiong Zhao, Zhuhua Wu, Hua Zhang, Jianping Liu, Xiaofang Cheng, Jiequn Wu, Huaiyu Yang, Hualiang Jiang, Lifeng Pan*, Wen Liu*. 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, 23(3), 352-360.

28.     Qingfei Zheng, Zhenhua Tian, Wen Liu*. Recent advances in understanding the enzymatic reactions of [4+2] cycloaddition and spiroketalization. Current Opinion in Chemical Biology 2016, 31, 95-102.

29.    Qunfei Zhao#, Min Wang#, Dongxiao Xu, Qinglin Zhang, Wen Liu*. Metabolic coupling of two small-molecule thiols programs the biosynthesis of lincomycin A. Nature 2015, 518(7537), 115-119.

30.    Zhenhua Tian#, Peng Sun#, Yan Yan#, Zhuhua Wu, Qingfei Zheng, Shuaixiang Zhou, Hua Zhang, Futao Yu, Xinying Jia, Dandan Chen, Attila Mándi, Tibor Kurtán, Wen Liu*. An enzymatic [4+2] cyclization cascade creates the pentacyclic core of pyrroindomycins. Nature Chemical Biology 2015, 11(4), 259-265.

31.    Qingfei Zheng#, Qinglan Wang#, Shoufeng Wang#, Jiequn Wu, Qian Gao*, Wen Liu*. Thiopeptide antibiotics exhibit a dual mode of action against intracellular pathogens by affecting both host and microbe. Chemistry & Biology 2015, 22(8), 1002-1007.

32.    Min Wang, Qunfei Zhao, Wen Liu*. The versatile low-molecular-weight thiols: Beyond cell protection.Bioessays 2015, 37, 1262–1267.

33.    Heng Guo, Jiang Wang, Yeming Li, Yi Yu, Qingfei Zheng, Jiequn Wu, Wen Liu*. Insight into bicyclic thiopeptide benefited from development of a uniform approach for molecular engineering and production improvement. Chemical Science 2014, 5, 240-246.

34.    Yan Yan, Jing Chen, Lihan Zhang, Qingfei Zheng, Ying Han, Hua Zhang, Daozhong Zhang, Takayoshi Awakawa, Ikuro Abe, Wen Liu*. Multiplexing of combinatorial chemistry in antimycin biosynthesis: expansion of molecular diversity and utility. Angewandte Chemie-International Edition 2013, 52(47), 12308-12312.

35.     Peng Sun, Qunfei Zhao, Futao Yu, Hua Zhang, Zhuhua Wu, Yinyan Wang, Yan Wang, Qinglin Zhang, Wen Liu*. Spiroketal formation and modification in avermectin biosynthesis involves a dual activity of AveC. Journal of the American Chemical Society 2013, 135(4), 1540-1548.

36.     Qi Zhang, Bo Pang, Wei Ding, Wen Liu*. Aromatic polyketides produced by bacterial iterative type I polyketide synthases. ACS Catalysis 2013, 3(7), 1439-1447.

37.     Qi Zhang, Wen Liu*. Biosynthesis of thiopeptide antibiotics and their pathway engineering. Natural Product Reports 2013, 30(2), 218-226.

38.     Shoufeng Wang, Shuaixiang Zhou, Wen Liu*. Opportunities and challenges from current investigations into the biosynthetic logic of nosiheptide-represented thiopeptide antibiotics. Current Opinion in Chemical Biology 2013, 17(4), 626-634.

39.     Qiongqiong Wu, Zhuhua Wu, Xudong Qu*, Wen Liu*. Insights into pyrroindomycin biosynthesis reveal a uniform paradigm for tetramate/tetronate formation. Journal of the American Chemical Society 2012, 134(42), 17342-17345.

40.    Xudong Qu*, Bo Pang, Zhicong Zhang, Ming Chen, Zhuhua Wu, Qunfei Zhao, Qinglin Zhang, Yinyan Wang, Yun Liu, Wen Liu*. Caerulomycins and collismycins share a common paradigm for 2,2’-bipyridine biosynthesis via an unusual hybrid polyketide-peptide assembly logic. Journal of the American Chemical Society 2012, 134(22), 9038-9041.

41.    Qi Zhang, Wilfred A. van der Donk, Wen Liu*. Radical-mediated enzymatic methylation: a tale of two SAMS. Accounts of Chemical Research 2012, 45(4), 555-564.

42.    Lian Duan#, Shoufeng Wang#, Rijing Liao, Wen Liu*. Insights into quinaldic acid formation in thiostrepton biosynthesis facilitating fluorinated thiopeptide generation. Chemistry & Biology 2012, 19(4), 443-448.

43.    Xudong Qu, Chun Lei, Wen Liu*. Transcriptome mining of active biosynthetic pathways and their associated products in Streptomyces flaveolus. Angewandte Chemie-International Edition 2011, 50(41), 9651-9654.

44.    Qi Zhang, Yuxue Li, Dandan Chen, Yi Yu, Lian Duan, Ben Shen, Wen Liu*. Radical-mediated enzymatic carbon chain fragmentation-recombination. Nature Chemical Biology 2011, 7(3), 154-160.

45.    Rijing Liao, Wen Liu*. Thiostrepton maturation involving a deesterification-amidation way to process the C-terminally methylated peptide backbone. Journal of the American Chemical Society 2011, 133(9), 2852-2855.

46.    Yi Yu, Heng Guo, Qi Zhang, Lian Duan, Ying Ding, Rijing Liao, Chun Lei, Ben Shen, Wen Liu*. NosA catalyzing carboxyl-terminal amide formation in nosiheptide maturation via an enamine dealkylation on the serine-extended precursor peptide. Journal of the American Chemical Society 2010, 132(46), 16324-16326.

47.    Wei Ding, Chun Lei, Qingli He, Qinglin Zhang, Yurong Bi, Wen Liu*. Insights into bacterial 6-methylsalicylic acid synthase and its engineering to orsellinic acid synthase for spirotetronate generation. Chemistry & Biology 2010, 17(5), 495-503.

48.    Rijing Liao, Lian Duan, Chun Lei, Haixue Pan, Ying Ding, Qi Zhang, Daijie Chen, Ben Shen, Yi Yu*, Wen Liu*. Thiopeptide biosynthesis featuring ribosomally synthesized precursor peptides and conserved posttranslational modifications. Chemistry & Biology 2009, 16(2), 141-147.

49.    Qunfei Zhao, Qingli He, Wei Ding, Mancheng Tang, Qianjin Kang, Yi Yu, Wei Deng, Qi Zhang, Jie Fang, Gongli Tang, Wen Liu*. Characterization of the azinomycin B biosynthetic gene cluster revealing a different iterative type I polyketide synthase for naphthoate biosynthesis. Chemistry & Biology 2008, 15(7), 693-705.

50.    Xin-Ying Jia, Zhen-Hua Tian, Lei Shao, Xu-Dong Qu, Qun-Fei Zhao, Jian Tang, Gong-Li Tang*, Wen Liu*. Genetic characterization of the chlorothricin gene cluster as a model for spirotetronate antibiotic biosynthesis. Chemistry & Biology 2006, 13(6), 575-585.

承担科研项目情况

国家重点研发计划“病原学与防疫技术体系研究”重点专项(2022YFC2303100),生物合成研究驱动的新型微生物抗感染药物创制,202212-202511月,项目负责人;

国家自然科学基金重大项目(22193070),天然产物来源药物的生物合成与分子创新,202201-202612月,项目负责人;

国家自然科学基金重点项目(32030002),富硫细菌环肽类代谢产物的翻译后修饰、调控机制以及结构与功能的多样性研究,202101-202512月,项目负责人;

国家自然科学基金应急管理项目(21750004),大环天然产物的模板化生物合成及其活性与结构导向的分子创新研究,201801-202012月,项目负责人;

国家自然科学国际(地区)合作与交流重点项目(21520102004),以多样性为导向的天然产物生物合成研究,201601-202012月,项目负责人;

国家自然科学基金重点项目(31430005),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,201501-201912月,项目负责人;

国家自然科学基金重点项目(20832009),天然产物独特结构单元的生物合成机制研究,200901-201212月,项目负责人。