加入收藏 | English

刘文

作者: 时间:2020-04-08 点击数:

刘文 博士

中国科学院研究员

生命有机国家重点实验室副主任

湖州生物制造创新中心主任、理事

中国科学院上海有机化学研究所

生命有机国家重点实验室

上海市零陵路345号,邮编200032

电话:(21) 54925111

E-mail: wliu@mail.sioc.ac.cn

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)研究员。

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。

工作经历

 20038月至今:入选中国科学院“<>计划”,上海有机化学研究所,研究员

 20019月至20037月:美国威斯康星大学麦迪逊分校药学院,研究助理

 20009月至20018月:美国加州大学戴维斯分校化学系,博士后

教育背景

 19949月至20008月:中国协和医科大学(中国医学科学院)获硕士(1997年)、博士学位(2000年,美国加州大学戴维斯分校化学系联合培养),导师:李元教授、沈奔教授。

 19889月至19927月:四川大学生物工程系,获学士学位。

主要获奖情况

 2017年国家“万人计划”科技创新领军人才;

 2017年中国科学院优秀导师奖;

 2017年工业生物技术年度创新先锋奖;

 2015年谈家桢生命科学创新奖;

 2015年科技部中青年科技创新领军人才;

 2015年国家百千万人才工程“有突出贡献中青年专家”;

 2013年日本化学会“Distinguished Lectureship Award”获得者;

 2013年上海市优秀学术带头人;

 2012年上海市领军人才;

 2012年中国科学院优秀研究生指导教师;

 2011年中国科学院优秀导师奖;

 2010年国务院政府特贴获得者;

 2010年中国药学会-赛诺菲安万特青年生物奖;

 2010年明治乳业生命科学奖(优秀奖);

 2009年中科院“<>计划”终期评估“优秀”入选者;

国家自然科学基金委2005年度“杰出青年基金”获得者;

上海市科学技术委员会2005年度“启明星计划”、2009年“启明星追踪计划”和“浦江人才计划”入选者

学术任职

 Cell杂志子刊《Cell Chemical Biology》编委;

英国皇家化学会《Natural Product Reports》编委;

Synthetic and Systems Biotechnology》编委;

《有机化学》编委;

中国微生物学会分子微生物学与生物工程专业委员会委员;

中国微生物学会分子生物学专业委员会委员;

中国医药生物技术协会酶工程与发酵工程专业委员会常务委员;

中国化学会化学生物学专业委员会委员

代表性论文

1. Zhang, D.; Zhang, F.; Liu, W., 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, 3993−4001.

2. Jia, L.; Tang, H.; Wang, W.; Yuan, T.; Wei, W.; Pang, B.; Gong, X.; Wang, S.; Li, Y.; Zhang, D.; Liu, W.*; Tang, W.*, A linear nonribosomal octapeptide from Fusarium graminearum facilitates cell-to-cell invasion of wheat. Nature Communications 2019, 10, 922.

3. Qiu, Y.; Du, Y.; Wang, S.; Zhou, S.; Guo, Y.; Liu, W., Radical S‑adenosylmethionine protein NosN forms the side ring system of nosiheptide by functionalizing the polythiazolyl peptide S‑conjugated indolic moiety. Organic Letters 2019, 21, 1502−1505.

4. Wang, J.; Lin, Z.; Bai, X.; Tao, J.; Liu, W., Optimal design of thiostrepton-derived thiopeptide antibiotics and their potential application against oral pathogens. Organic Chemistry Frontiers 2019, 6, 1194–1199.

5. Liu, J.; Lin, Z.; Li, Y.; Zheng, Q.; Chen, D.; Liu, W., Insights into the thioamidation of thiopeptins to enhance the understanding of the biosynthetic logic of thioamide-containing thiopeptides. Organic & Biomolecular Chemistry 2019, 17, 3727–3731.

6. Chen, D.; Zhao, Q.; Liu, W., Discovery of caerulomycin/collismycin‑type 2,2’‑bipyridine natural products in the genomic era. Journal of Industrial Microbiology & Biotechnology 2019, 46, 459-468.

7. Liu, J.; Lin, Z.; Chen, H.; Guo, H.; Tao, J.; Liu, W., Biosynthesis of the central piperidine nitrogen heterocycle in series a thiopeptides. Chinese Journal of Chemistry 2019, 37, 35-41.

8. Zhang, D.; Tang, Z.; Liu, W., Biosynthesis of lincosamide antibiotics: reactions associated with degradation and detoxification pathways play a constructive role. Accounts of Chemical Research 2018, 51(6), 1496-1506.

9. Zhong, G.; Chen, H.; Liu, W., Reply to ‘C–C bond cleavage in biosynthesis of 4-alkyl-L-proline precursors of lincomycin and anthramycin cannot precede C-methylation’. Nature Communications 2018, doi: 10.1038/s41467-018-05500-1.

10. Awakawa, T.; Fujioka, T.; Zhang, L.; Hoshino, S.; Hu, Z.; Hashimoto, J.; Kozone, I.; Ikeda, H.; Shin-Ya, K.; Liu, W.; Abe, I., Reprogramming of the antimycin NRPS-PKS assembly lines inspired by gene evolution. Nature Communications 2018, 9, 3534.

11. Zheng, Q.; Gong, Y.; Guo, Y.; Zhao, Z.; Wu, Z.; Zhou, Z.; Chen, D.; Pan, L.*; Liu, W.*, Structural insights into a flavin-dependent [4+2] cyclase that catalyzes trans-decalin formation in pyrroindomycin biosynthesis. Cell chemical biology 2018, 25, 718-727.

12. Wang, M.; Chen, D.; Zhao, Q.; Liu, W., Isolation, structure elucidation, and biosynthesis of a cysteate-containing nonribosomal peptide in Streptomyces lincolnensis. Journal of Organic Chemistry 2018, 83(13), 7102-7108.

13. Li, J.; Li, Y.; Niu, G.; Guo, H.; Qiu, Y.; Lin, Z..; Liu, W.*; Tan, H.*, NosP-Regulated Nosiheptide Production Responds to Both Peptidyl and Small-Molecule Ligands Derived from the Precursor Peptide. Cell chemical biology 2018, 25, 143-153.

14. Qiu, Y.; Du, Y.; Zhang, F.; Liao, R.; Zhou, S.; Peng, C.; Guo, Y.; Liu, W., 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, 18186-18189.

15. Lin, Z.; Ji, J.; Zhou, S.; Zhang, F.; Wu, J.; Guo, Y.; Liu, W., 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, 12105-12108.

16. Zhong, G.; Zhao, Q.; Zhang, Q.; Liu, W., 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, 8, 16109.

17. Chen, M.; Liu, J.; Duan, P.; Li, M.; Liu, W., Biosynthesis and molecular engineering of templated natural products. National Science Review, 2017, doi: 10.1093/nsr/nww045.

18. Lin, Z.; He, Q.; Liu, W., Bio-inspired Engineering of Thiopeptide Antibiotics advances the Expansion of Molecular Diversity and Utility. Current Opinion in Biotechnology 2017, 48, 210-219.

19. Chen, M.; Zhang, Y.; Du, Y.; Zhao, Q.; Zhang, Q.; Wu, J.; Liu, W., Enzymatic Competition and Cooperation Branch the Caerulomycin Biosynthetic Pathway toward Different 2,2'-bipyridine members. Organic & Biomolecular Chemistry 2017, 15, 5472-5475.

20. Chen, M.; Pang, B.; Du, Y.; Zhang, Y.; Liu, W., Characterization of the Metallo-dependent Amidohydrolases Responsible for "auxiliary" Leucinyl Removal in the Biosynthesis of 2,2'-bipyridine Antibiotics. Synthetic and Systems Biotechnology 2017, 2, 137-146.

21. Zheng, Q.; Fang, H.; Liu, W., Post-translational modifications involved in the biosynthesis of thiopeptide antibiotics. Organic & Biomolecular Chemistry 2017, 15, 3376-3390.

22. Li, X.; Zheng, Q.; Yin, J.; Liu, W.*; Gao, S.*, Chemo-enzymatic Synthesis of Equisetin. Chemical Communications 2017, 53, 4695-4697

23. Zheng, Q.#; Wu, Z.#; Sun, P.#; Chen, D.; Tian, Z.; Liu, W., A linear hydroxymethyl tetramate undergoes an acetylation–elimination process for exocyclic methylene formation in the biosynthetic pathway of pyrroindomycins. Organic & Biomolecular Chemistry 2017, 15, 88-91.

24. Zheng, Q.; Wang, S.; Duan, P.; Liao, R.; Chen, D.; Liu, W., 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, 113 (50):14318-14323.

25. Zheng, Q.; Wang, S.; Liao, R.; Liu, W., Precursor-Directed Mutational Biosynthesis Facilitates the Functional Assignment of Two Cytochromes P450 in Thiostrepton Biosynthesis, ACS Chemical Biology 2016, 11, 2673-2678

26. Duan, P.; Zheng, Q.; Lin, Z.; Wang, S.; Chen, D.; Liu, W., Molecular engineering of thiostrepton via single “base”-based mutagenesis to generate side ring-derived variants. Organic Chemistry Frontiers 2016, 3, 1254-1258

27. Wang, M.; Zhao, Q.; Zhang, Q.; Liu, W., Differences in PLP-Dependent Cysteinyl Processing Lead to Diverse S‑Functionalization of Lincosamide Antibiotics. Journal of the American Chemical Society 2016, 138, 6348-6351

28. Pang, B.; Zhong, G.; Tang, Z.; Liu, W., Enzymatic [4+2] Cycloadditions in the Biosynthesis of Spirotetramates and Spirotetronates. Methods in Enzymology 2016, 575, 39-63

29. Lin, Z.; Chen, D.; Liu, W., .Biosynthesis-based artificial evolution of microbial natural products, SCIENCE CHINA Chemistry 2016, 59, 1175-1189

30. Zheng, Q.; Guo, Y.; Yang, L.; Zhao, Z.; Wu, Z.; Zhang, H.; Liu, J.; Cheng, X.; Wu, J.; Yang, H.; Jiang, H.; Pan, L.; Liu, W., 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, 352-360 (Featured Article).

31. Zheng, Q.; Tian, Z.; Liu, W., Recent advances in understanding the enzymatic reactions of [4+2] cycloaddition and spiroketalization. Current Opinion of Chemical Biology 2016, 31, 95-102.

32. Pang, B.; Wang, M.; Liu, W., Cyclization of polyketides and non-ribosomal peptides on and off their assembly lines. Natural Product Reports 2016, 33, 162-173.

33. Wang, S.; Zheng, Q.; Wang, J.; Chen, D.; Yu, Y.; Liu, W., 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, 3, 496-500.

34. Li, Y.; Li, J.; Tian, Z.; Xu, Y.; Zhang, J.; Liu, W.*; Tan, H.*, Coordinative modulation of chlorothricin biosynthesis by binding of the glycosylated intermediates and end product to a responsive regulator ChlF1. Journal of Biological Chemistry 2016, 291, 5406-5417.

35. Zheng, Q.; Liu, W., Thiopeptide Antibiotics act on both Host and Microbe to Deliver Double Punch on Mycobacterial Infection. Mycobacterial Diseases 2016, 6, 203.

36. Zhao, Q.; Wang, M.; Xu, D.; Zhang, Q.; Liu, W., Metabolic coupling of two small-molecule thiols programs the biosynthesis of lincomycin A. Nature 2015, 518, 115-119 (Featured in: Melancon III, C. Elusive source of sulfur unravelled. Nature 2015, 518, 45-46; Abe, I., Zhang, L. F1000Prime 2015, doi: 10.3410/f.725320497.7933503602; Crawford, J., Torring, T. F1000Prime 2015, doi: 10.3410/f.725320497.7933503765).

37. Tian, Z.; Sun, P.; Yan, Y.; Wu, Z.; Zheng, Q.; Zhou, X.; Zhang, H.; Yu, F.; Jia, X.; Chen, D.; Mandi, A.; Kurtan, T.; Liu, W., An enzymatic [4+2] cyclization cascade creates the pentacyclic core of pyrroindomycins. Nature Chemical Biology 2015, 11, 259-265.

38. Wang, M.; Zhao, Q.; Liu, W., The versatile low-molecular-weight thiols: Beyond cell protection. Bioessays 2015, 37, 1262–1267.

39. Zheng, Q.; Wang, Q.; Wang, S.; Wu, J.; Gao, Q.; Liu, W., Thiopeptide antibiotics exhibit a dual mode of action against intracellular pathogens by affecting both host and microbe. Chemistry & Biology 2015, 22, 1002-1007 (Featured Article and Featured in: Wilkinson, B.; Alt, S. F1000Prime 2015, doi: 10.3410/f.725675341.793510399).

40. Sun, P.; Zhao, Q.; Wu, Z.; Zhang, W.; Liu, W., 1,19-seco-Avermectin Analogues from a ΔaveCDE Mutant Streptomyces avermectinius Strain. Journal of Natural Products 2015, 78, 301-305.

41. Wang, S.; Zheng, Q.; Wang, J.; Zhao, Z.; Li, Q.; Yu, Y.; Wang, R.; Liu, W., Target-oriented design and biosynthesis of thiostrepton-derived thiopeptide antibiotics with improved pharmaceutical properties. Organic Chemistry Frontiers 2015, 2, 106-109.

42. Liu, S.; Guo, H.; Zhang, T.; Han, L.; Yao, P.; Zhang, Y.; Rong, N.; Yu, Y.; Lan, W.; Wang, C.; Ding, J.; Wang, R.; Liu, W.*; Cao, C.*, Structure-based mechanistic insights into terminal amide synthase in nosiheptide-represented thiopeptides biosynthesis. Scientific Reports 2015, 5,12744. doi: 10.1038/srep12744.

43. Medema, M. H.; Kottmann, R.; Yilmaz, P.; Cummings, M.; Biggins, J. B.; Blin, K.; Bruijn, I., d.; Chooi, Y. H.; Claesen, J.; Coates, R. C.; Cruz-Morales, P.; Duddela, S.; Düsterhus, S.; Edwards, D. J.; Fewer, D. P.; Garg, N., Geiger, C.; Gomez-Escribano, J. P.; Greule, A. Hadjithomas, M., Haines, A. S., Helfrich, E. J. N., Hillwig, M. L., Ishida, K., Jones, A. C., Jones, C. S.; Jungmann, K.; Kegler, C.; Kim, H. U.; Kötter, P.;Krug, D.; Masschelein, J.; Melnik, A. V.; Mantovani, S. M.; Monroe, E. A.; Moore, M.; Moss, N.; Nützmann, H-W.; Pan, G.; Pati, A.; Petras, D.; Reen, F. J.; Rosconi, F.; Rui, Z.; Tian, Z.; Tobias, N. J.; Tsunematsu, Y.; Wiemann, P.; Wyckoff, E.; Yan, X.; Yim, G.; Yu, F.; Xie, Y.; Aigle, B.; Apel, A. K.; Balibar, C. J.; Balskus, E. P.; Barona-Gómez, F.; Bechthold, A.; Bode, H. B.; Borriss, R.; Brady, S. F.; Brakhage, A. A.; Caffrey, P.; Cheng, Y-Q.; Clardy, J.; Cox, R. J.; Mot, R. D.; Donadio, S.; Donia, M. S.; van der Donk, W. A.; Dorrestein, P. C.; Doyle, S.; Driessen, A. J. M.; Ehling-Schulz, M.; Entian, K-D.; Fischbach, M. A.; Gerwick, L.; Gerwick, W. H.; Gross, H.; Gust, B.; Hertweck, C.; Höfte, M.; Jensen, S. E.; Ju, J.; Katz, L.; Kaysser, L.; Klassen, J. L.; Keller, N. P.; Kormanec, J.; Kuipers, O. P., Kuzuyama, T., Kyrpides, N. C., Kwon, H-j., Lautru, S., Lavigne, R., Lee, C. Y., Bai, L.; Liu, X.; Liu, W.; Luzhetskyy, A.; Mahmud, T.; Mast, Y.; Méndez, C.; Metsä-Ketelä, N.; Micklefield, J.; Mitchell, D. A.; Moore, B. S.; Moreira, L. M.; Müller, R.; Neilan, B. A.; Nett, M.; Nielsen, J.; O'Gara, F.; Oikawa, H.; Osbourn, A.; Osburne, M. S.; Ostash, B.; Payne, S. M.; Pernodet, J-L.; Petricek, M.; Piel, J.; Ploux, O.; Raaijmakers, J. M.; Salas, J. A.; Schmitt, E. K.; Scott, B.; Seipke, R. F.; Shen, B.; Sherman, D. H.; Sivonen, K.; Smanski, M. J.; Sosio, M.; Stegmann, E.; Süssmuth, R. D.; Tahlan, K.; Thomas, C. M.; Tang, Y.; Truman, A. W.; Viaud, M.; Walton, J. D.; Walsh, C. T.; Weber, T.; van Wezel, G. P.; Wilkinson, B.; Willey, J. M.; Wohlleben, W.; Wright, G. D.; Ziemert, N.; Zhang, C.; Zotchev, S. B.; Breitling, R.; Takano, E.; Glöckner, F. O., Minimum information about a biosynthetic gene cluster. Nature Chemical Biology 2015, 11, 265-231.

44. Zhang, L.; Mori, T.; Zheng, Q.; Awakawa, T.; Yan, Y.; Liu, W.; Abe, I., Rational control of polyketide extender units by structure-based engineering of a crotonyl-CoA carboxylase/reductase in antimycin biosynthesis. Angewandte Chemie International Edition 2015, 54, 13462–13465.

45. Chang, C.; Huang, R.; Yan, Y.; Ma, H.; Dai, Z.; Zhang, B.; Deng, Z.; Liu, W.; Qu, X., Uncovering the formation and selection of benzylmalonyl-CoA from the biosynthesis of splenocin and enterocin reveals a versatile way to introduce amino acids into polyketide carbon scaffolds. Journal of the American Chemical Society 2015, 137, 4183-4190.

46. Wang, Y.; Liu, S.; Yao, P.; Yu, Y.; Zhang, Y.; Lan, W.; Wang, C.; Ding, J.;, Liu, W.; Cao, C., Crystallographic analysis of NosA, which catalyzes terminal amide formation in the biosynthesis of nosiheptide. Acta Crystallogr F 2015, 71, 1033-1037.

47. Pang, B.; Zheng, Q.; Liu, W., Synthetic biology in natural medicine research. Scientia Sinica Vitae 2015, 45, 1015-1026.

48. Chen, D.; Wu, J.; Liu, W., Biosynthesis-based production improvement and structure modification of erythromycin A. Chinese Journal of Biotechnology 2015, 31, 939-954.

49. Zheng, Q.; Wang, S.; Liu, W., Discovery and effi cient synth esis of a biolo gically active alkaloid inspired by thiostrepton biosynthesis. Tetrahedron 2014, 70, 7686-7690.

50. Sun, P.; Zhao, Q.; Zhang, H.; Wu, J.; Liu, W., Effect of Stereochemistry of Avermectin-Like 6,6-Spiroketals on Biological Activities and Endogenous Biotransformations in Streptomyces avermectinius.ChemBioChem 2014, 15(5), 660-664.

51. Guo, H.; Wang, J.; Li, Y.; Yu, Y.; Zheng, Q.; Wu, J.; Liu, W., Insight into bicyclic thiopeptide benefited from development of a uniform approach for molecular engineering and production improvement, Chemical Science 2014, 5, 240-246.

52. Bai, T.; Zhang, D.; Lin, S.; Long, Q.; Wang, Y.; Ou, H.; Kang, Q.; Deng, Z.; Liu, W.; Tao, M., Operon for biosynthesis of lipstatin, the Beta-lactone inhibitor of human pancreatic lipase. Applied and Environmental Microbiology 2014, 80(24), 7473-7483.

53.  Yan, Y.; Chen, J.; Zhang, L.; Zheng, Q.; Han, Y.; Zhang, H.; Zhang, D.; Awakawa, T.; Abe, I.; Liu, W. Multiplexing of combinatorial chemistry in antimycin biosynthesis: expansion of molecular diversity and utility. Angewandte Chemie International Edition 2013, 39, 12308-12312.

54. Sun, P.; Zhao, Q.; Yu, F.; Zhang, H.; Wu, Z.; Wang, Y-Y.; Wang, Y.; Liu, W., Spiroketal formation and modification in avermectin biosynthesis involves a dual activity of AveC. Journal of the American Chemical Society 2013, 135 (4), 1540-1548 (Hot off the press. Nat. Prod. Rep. 2013).

55. Wang, S.; Zhou, S.; Liu, W., Opportunities and challenges from current investigations into the biosynthetic logic of nosiheptide-represented thiopeptide antibiotics. Current Opinion in Chemical Biology 2013, 17, 626-634.

56. Chen, D.; Zhang, L.; Pang, B.; Chen, J.; Xu, Z.; Abe, I.; Liu, W., FK506 maturation involves a cytochrome P450 protein-catalyzed four electron oxidation in parallel with C-31 O-methylation. Journal of Bacteriology 2013, 195(9), 1931-1939.

57. Shao, L.; Chen, J.; Wang, C.; Li, J.; Tang, Y.; Chen, D.; Liu, W., Characterization of a key aminoglycoside phosphotransferase in gentamicin biosynthesis. Bioorganic & Medicinal Chemistry Letters 2013, 23(5), 1438-1441.

58. Zhang, Q.; Liu, W., Biosynthesis of thiopeptide antibiotics and their pathway engineering. Natural Product Reports 2013, 30, 218-226.

59. Zhang, Q.; Pang, B.; Ding, W.; Liu, W.*, Aromatic polyketide produced by bacterial iterative type I polyketide synthases. ACS Catalysis 2013, 3(7), 1439-1447.

60. Arnison, P. G.; Bibb, M. J.; Bierbaum, G.; Bowers, A. A.; Bugni, T. S.; Bulaj, G.; Camarero, J. A.; Campopiano, D. J.; Challis, G. L.; Clardy, J.; Cotter, P. D.; Craik, D. J.; Dawson, M.; Dittmann, E.; Donadio, S.; Dorrestein, P. C.; Entian, K. D.; Fischbach, M. A.; Garavelli, J. S.; Goransson, U.; Gruber, C. W.; Haft, D. H.; Hemscheidt, T. K.; Hertweck, C.; Hill, C.; Horswill, A. R.; Jaspars, M.; Kelly, W. L.; Klinman, J. P.; Kuipers, O. P.; Link, A. J.; Liu, W.; Marahiel, M. A.; Mitchell, D. A.; Moll, B. S. Moore, R. Muller, S. K. Nair, I. F. Nes, G. E. Norris, B. M. Olivera, H. Onaka, M. L. Patchett, G. N.; Piel, J.; Reaney, M. J.; Rebuffat, S.; Ross, R. P.; Sahl, H. G.; Schmidt, E. W.; Selsted, M. E.; Severinov, K.; Shen, B.; Sivonen, K.; Smith, L.; Stein, T.; Sussmuth, R. D.; Tagg, J. R.; Tang, G. L.; Truman, A. W.; Vederas, J. C.; Walsh, C. T.; Walton, J. D.; Wenzel, S. C.; Willey J. M.; van der Donk, W. A. Natural Product Reports 2013, 30, 108-160.

61. Wu, Q.; Wu, Z.; Qu, X.; Liu, W., Insights into pyrroindomycin biosynthesis reveal a uniform paradigm for tetromate/tetronate formation. Journal of the American Chemical Society 2012, 134, 17342-17345.

62. Duan, L.; Wang, S.; Liao, R.; Liu, W., Insights into quinaldic acid formation in thiostrepton biosynthesis facilitating fluorinated thiopeptide generation. Chemistry & Biology 2012, 19 (4), 443-448.

63. Qu, X.; Pang, B.; Zhang, Z.; Chen, M.; Wu, Z.; Zhao, Q.; Zhang, Q.; Wang, Y.; Liu, Y.; Liu, W., 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.

64. Zhang, Q,; van der Donk, W. A.; Liu, W., Radical-mediated enzymatic methylation: a tale of two SAMS. Accounts of Chemical Research 2012, 45 (4), 555-564.

65. Chen, D.; Zhang, Q.; Zhang, Q.; Cen, P.; Xu, Z.; Liu, W., 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, 78 (15), 5093-5103.

66. Smanski, M. J.; Qu, X. D.; Liu, W., Shen, B. Biosynthesis of pharmaceutical natural products and their pathway engineering. In Breakthoughs and Perspectives in Organic Chemistry——Views Based on the Achievements in the First Decade of the 21th Century. Ding, K. L; Dai, L. X. Eds. John Wiley-VCH Verlag GmbH & Co. KGaA, 2011, pp125-180.

67. Yan, Y.; Zhang, L.; Ito, T.; Qu, X.; Asakawa, Y.; Awakawa, T.; Abe, I.; Liu, W., Biosynthetic pathway for high structural diversity of a common dilactone core in antimycin production. Organic Letter 2012, 14 (16), 4142-4145.

68. Li, J.; Qu, X.; He, X.; Duan, L.; Wu, G.; Bi, D.; Deng, Z.; Liu, W.*; Ou, H. Y.*, ThioFinder: a web-based tools for the identification of thiopeptide gene clusters in DNA sequence. PloS One 2012, 7 (9), e45878.

69. Qu, X. D.; Lei, C.; Liu, W., Transcriptome mining of active biosynthetic pathways and their associated products in Streptomyces flaveolus. Angewandte Chemie International Edition 2011, 50, 9651-9654.

70. Wu, J. Q.; Zhang, Q. L.; Deng, W.; Qian, J. C.; Zhang, S. L.; Liu, W., 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, 77 (21), 7508-7516.

71. Zhang, Q.; Liu, W., Complex biotransformations catalyzed by radical S-adenosylmethionine enzymes. Journal of Biological Chemistry 2011, 286 (35), 30245-30252.

72. Zhang, Q.; Li, Y. X.; Chen, D. D.; Yu, Y.; Duan, L. A.; Shen, B.; Liu, W., Radical-mediated enzymatic carbon chain fragmentation-recombination. Nature Chemical Biology 2011, 7 (3), 154-160 (Featured in: BIOCHEMISTRY targeting tryptophan. Science 2011, 311, 1366; Radical break-up, blissful make-up. Nat. Chem. Biol. 2011, 7, 133-134; Chemical biology: radical transformation. Nat. China 2011, doi: 10.1038/nchina.2011.9; Faculty of 1000 2011, post-publication peer review).

73. Liao, R. J.; Liu, W., 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.

74. Qu, X. D.; Jiang, N.; Xu, F.; Shao, L.; Tang, G. L.; Wilkinson, B.; Liu, W., Cloning, sequencing and characterization of the biosynthetic gene cluster of sanglifehrin A, a potent cyclophilin inhibitor. Molecular Biosystems 2011, 7 (3), 852-861 (Featured in: Faculty of 1000 2011, post-publication peer review).

75. Zhang, Q.; Chen, D. D.; Lin, J.; Liao, R. J.; Tong, W.; Xu, Z. N.; Liu, W., Characterization of NocL Involved in Thiopeptide Nocathiacin I Biosynthesis A 4Fe-4S CLUSTER AND THE CATALYSIS OF A RADICAL S-ADENOSYLMETHIONINE ENZYME. Journal of Biological Chemistry 2011, 286 (24), 21287-21294.

76. Zhang, Q.; Wu, J.; Qian, J.; Chu, J.; Zhuang, Y.; Zhang, S.; Liu, W., 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, 52 (2), 129-137.

77. Ding, W.; Deng, W.; Tang, M. C.; Zhang, Q.; Tang, G. L.; Bi, Y. R.; Liu, W., Biosynthesis of 3-methoxy-5-methyl naphthoic acid and its incorporation into the antitumor antibiotic azinomycin B. Molecular Biosystems 2010, 6 (6), 1071-1081.

78. Ding, W.; Lei, C.; He, Q. L.; Zhang, Q. L.; Bi, Y. R.; Liu, W., Insights into Bacterial 6-Methylsalicylic Acid Synthase and Its Engineering to Orsellinic Acid Synthase for Spirotetronate Generation. Chemistry & Biology 2010, 17 (5), 495-503.

79. Ding, Y.; Yu, Y.; Pan, H. X.; Guo, H.; Li, Y. M.; Liu, W., Moving posttranslational modifications forward to biosynthesize the glycosylated thiopeptide nocathiacin I in Nocardia sp ATCC202099. Molecular Biosystems 2010, 6 (7), 1180-1185.

80. Wang, J.; Yu, Y.; Tang, K. X.; Liu, W.; He, X. Y.; Huang, X.; Deng, Z. X., Identification and Analysis of the Biosynthetic Gene Cluster Encoding the Thiopeptide Antibiotic Cyclothiazomycin in Streptomyces hygroscopicus 10-22. Applied and Environmental Microbiology 2010, 76 (7), 2335-2344.

81. Yu, Y.; Guo, H.; Zhang, Q.; Duan, L. A.; Ding, Y.; Liao, R. J.; Lei, C.; Shen, B.; Liu, W., 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.

82. He, Q. L.; Jia, X. Y.; Tang, M. C.; Tian, Z. H.; Tang, G.; Liu, W., Dissection of Two Acyl-Transfer Reactions Centered on Acyl-S-Carrier Protein Intermediates for Incorporating 5-Chloro-6-methyl-O-methylsalicyclic Acid into Chlorothricin. ChemBioChem 2009, 10 (5), 813-819.

83. Liao, R. J.; Duan, L.; Lei, C.; Pan, H. X.; Ding, Y.; Zhang, Q.; Chen, D. J.; Shen, B.; Yu, Y.; Liu, W., Thiopeptide Biosynthesis Featuring Ribosomally Synthesized Precursor Peptides and Conserved Posttranslational Modifications. Chemistry & Biology 2009, 16 (2), 141-147 (Featured in: This week in techniques: Biosynthetic pathway for the production of thiopeptide antibiotics. SciBX 2(10), 2009, Doi: 10.1038/scibx.2009.423; Thiopeptide antibiotic biosynthesis. Angew. Chem. Int. Ed. 2009, 486770-6773; Recent advances in thiopeptide antibiotic biosynthesis. Nat. Prod. Rep. 2010, 27, 153-164).

84. Yu, Y.; Duan, L.; Zhang, Q.; Liao, R. J.; Ding, Y.; Pan, H. X.; Wendt-Pienkowski, E.; Tang, G. L.; Shen, B.; Liu, W., Nosiheptide Biosynthesis Featuring a Unique Indole Side Ring Formation on the Characteristic Thiopeptide Framework. ACS Chemical Biology 2009, 4 (10), 855-864 (Featured in: Recent advances in thiopeptide antibiotic biosynthesis. Nat. Prod. Rep. 2010, 27, 153-164).

85. Liu, W.; Yu, Y, Combinatorial Biosynthesis of pharmaceutical natural products. Biocatalysis for the pharmaceutical industry-discovery, development and manufacturing. In Biocatalysis for the Pharmaceutical Industry. Tao, J. H.; Lin, G. Q.; Liese, A. Eds. John Wiley & Sons Pte Ltd, 2009, pp229-245.

86. Chen, Y.; Deng, W.; Wu, J. Q.; Qian, J. C.; Chu, J.; Zhuang, Y. P.; Zhang, S. L.; Liu, W., Genetic modulation of the overexpression of tailoring genes eryK and eryG leading to the improvement of erythromycin a purity and production in Saccharopolyspora erythraea fermentation. Applied and Environmental Microbiology 2008, 74 (6), 1820-1828.

87. Fang, J.; Zhang, Y. P.; Huang, L. J.; Jia, X. Y.; Zhang, Q.; Zhang, X.; Tang, G.; Liu, W., Cloning and characterization of the tetrocarcin a gene cluster from Micromonospora chalcea NRRL 11289 reveals a highly conserved strategy for tetronate biosynthesis in spirotetronate antibiotics. Journal of Bacteriology 2008, 190 (17), 6014-6025.

88. Galm, U.; Wang, L. Y.; Wendt-Pienkowski, E.; Yang, R. Y.; Liu, W.; Tao, M. F.; Coughlin, J. M.; Shen, B., In vivo manipulation of the bleomycin biosynthetic gene cluster in Streptomyces verticillus ATCC15003 revealing new insights into its biosynthetic pathway. Journal of Biological Chemistry 2008, 283 (42), 28236-28245.

89. Li, L.; Deng, W.; Song, J.; Ding, W.; Zhao, Q. F.; Peng, C.; Song, W. W.; Tang, G.; Liu, W., Characterization of the saframycin a gene cluster from Streptomyces lavendulae NRRL 11002 revealing a nonribosomal peptide synthetase system for assembling the unusual tetrapeptidyl skeleton in an iterative manner. Journal of Bacteriology 2008, 190 (1), 251-263.

90. Zhang, J.; Van Lanen, S. G.; Ju, J. H.; Liu, W.; Dorrestein, P. C.; Li, W. L.; Kelleher, N. L.; Shen, B., A phosphopantetheinylating polyketide synthase producing a linear polyene to initiate enediyne antitumor antibiotic biosynthesis. Proceedings of the National Academy of Sciences of the United States of America 2008, 105 (5), 1460-1465 (Featured in: Enediynes taught how to work better. C&E News 2007, 85, 25).

91. Zhao, Q. F.; He, Q. L.; Ding, W.; Tang, M. C.; Kang, Q. J.; Yu, Y.; Deng, W.; Zhang, Q.; Fang, J.; Tang, G.; Liu, W., 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 (Featured in: Antibiotic biosynthesis: from Genes to Enzymes. Nat. China 2008, Doi: 10.1038/nchina.2008.196).

92. Liu, W.; Zhang, S. L.; Chen, Y.; Deng, W.; Wu, J. Q., Improvement of Erythromycin a purity and production at the fermentation stage of Saccharopolyspora erytharea by metabolic engineering. Journal of Biotechnology 2008, 136 (Supplement 1): S21-S21.

93. Kennedy, D. R.; Gawron, L. S.; Ju, J. H.; Liu, W.; Shen, B.; Beerman, T. A., Single chemical modifications of the C-1027 enediyne core, a radiomimetic antitumor drug, affect both drug potency and the role of ataxia-telangiectasia mutated in cellular responses to DNA double-strand breaks. Cancer Research 2007, 67 (2), 773-781.

94. Shen, B.; Cheng, Y. Q.; Christenson, S. D.; Jiangi, H.; Ju, J. H.; Kwon, H. J.; Lim, S. K.; Liu, W.; Nonaka, K.; Seo, J. W.; Smith, W. C.; Standage, S.; Tang, G. L.; Van Lanen, S.; Zhang, J., Polyketide Biosynthesis beyond the Type I, II, and III Polyketide Synthase Paradigms: A Progress Report. In Polyketides: Biosynthesis, Biological Activity, and Genetic Engineering, Rimando, A. M.; Baerson, S. R., Eds. 2007; Vol. 955, pp 154-166.

95. Van Lanen, S. G.; Oh, T. J.; Liu, W.; Wendt-Pienkowski, E.; Shen, B., Characterization of the maduropeptin biosynthetic gene cluster from Actinomadura madurae ATCC 39144 supporting a unifying paradigm for enediyne biosynthesis. Journal of the American Chemical Society 2007, 129 (43), 13082-13094.

96. Jia, X. Y.; Tian, Z. H.; Shao, L.; Qu, X. D.; Zhao, Q. F.; Tang, J.; Tang, G.; Liu, W., Genetic characterization of the chlorothricin gene cluster as a model for spirotetronate antibiotic biosynthesis. Chemistry & Biology 2006, 13 (6), 575-585.

97. Shao, L.; Qu, X. D.; Jia, X. Y.; Zhao, Q. F.; Tian, Z. H.; Wang, M.; Tang, G.; Liu, W., Cloning and characterization of a bacterial iterative type I polyketide synthase gene encoding the 6-methylsalicyclic acid synthase. Biochemical and Biophysical Research Communications 2006, 345 (1), 133-139.

98. Liu, W.; Nonaka, K.; Nie, L. P.; Zhang, J.; Christenson, S. D.; Bae, J.; Van Lanen, S. G.; Zazopoulos, E.; Farnet, C. M.; Yang, C. F.; Shen, B., The neocarzinostatin biosynthetic gene cluster from Streptomyces carzinostaticus ATCC 15944 involving two iterative type I polyketide synthases. Chemistry & Biology 2005, 12 (3), 293-302.

99. Van Lanen, S. G.; Dorrestein, P. C.; Christenson, S. D.; Liu, W.; Ju, J. H.; Kelleher, N. L.; Shen, B., Biosynthesis of the beta-amino acid moiety of the enediyne antitumor antibiotic C-1027 featuring beta-amino acyl-S-carrier protein intermediates. Journal of the American Chemical Society 2005, 127 (33), 11594-11595.

100. Murrell, J. M.; Liu, W.; Shen, B., Biochemical characterization of the SgcA1 alpha-D-glucopyranosyl-1-phosphate thymidylyltransferase from the enediyne antitumor antibiotic C-1027 biosynthetic pathway and overexpression of sgcA1 in Streptomyces globisporus to improve C-1027 production. Journal of Natural Products 2004, 67 (2), 206-213.

101. Christenson, S. D.; Liu, W.; Toney, M. D.; Shen, B., A novel 4-methylideneimidazole-5-one-containing tyrosine aminomutase in enediyne antitumor antibiotic C-1027 biosynthesis. Journal of the American Chemical Society 2003, 125 (20), 6062-6063.

102. Liu, W.; Ahlert, J.; Gao, Q. J.; Wendt-Pienkowski, E.; Shen, B.; Thorson, J. S., Rapid PCR amplification of minimal enediyne polyketide synthase cassettes leads to a predictive familial classification model. Proceedings of the National Academy of Sciences of the United States of America 2003, 100 (21), 11959-11963.

103. Shen, B.; Liu, W.; Nonaka, K., Enediyne natural products: Biosynthesis and prospect towards engineering novel antitumor agents. Current Medicinal Chemistry 2003, 10 (21), 2317-2325.

104. Zazopoulos, E.; Huang, K. X.; Staffa, A.; Liu, W.; Bachmann, B. O.; Nonaka, K.; Ahlert, J.; Thorson, J. S.; Shen, B.; Farnet, C. M., A genomics-guided approach for discovering and expressing cryptic metabolic pathways. Nature Biotechnology 2003, 21 (2), 187-190.

105. Liu, W.; Christenson, S. D.; Standage, S.; Shen, B., Biosynthesis of the enediyne antitumor antibiotic C-1027. Science 2002, 297 (5584), 1170-1173 (featured in: New enzymes in warhead. Nat. Biotechnol. 2002, 20, 984-985; Towards bioengineering anticancer drugs. Chem. & Biol. 2002, 9, 956-958; Newly mapped bacterial genes may contain blueprints for new anticancer drugs. The lancet, 2002, 360, 550; Path to enediynes: Engineering of biosynthetic route could lead to better anticancer drugs. C&E News, 2002, 80, 33; Chemical Highlights 2002: Biochemistry. C&E News, 2002, 80, 40).

106. Liu, W.; Shen, B., Genes for production of the enediyne antitumor antibiotic C-1027 in Streptomyces globisporus are clustered with the cagA gene that encodes the C-1027 apoprotein. Antimicrobial Agents and Chemotherapy 2000, 44 (2), 382-392 (Featured in: Enediyne research continues apace. C&E News, 2000, 78, 47-49).

107. Thorson, J. S.; Shen, B.; Whitwam, R. E.; Liu, W.; Li, Y.; Ahlert, J., Enediyne biosynthesis and self-resistance: A progress report. Bioorganic Chemistry 1999, 27 (2), 172-188.


地址:河南省郑州市金水区文化路97号郑州大学北校区河南先进技术研究院 邮编:450003

Copyright© 2019 All Rights Reserved.河南先进技术研究院