Shanghai Institute of Organic Chemistry Wen Liu, Ph.D.
Research
Natural Product Biosynthesis (Genetics, Biochemistry and Chemistry)
Interests
Combinatorial Biosynthesis for Production Improvement and Structural
Genome Mining for Discovery of Novel Microbial Natural Products
Professional 2003–present: Professor, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, China Experiences 2001-2003: Research Associate, School of Pharmacy, University of Wisconsin- Madison, United States 2000–2001: Postdoctoral Fellow, Department of Chemistry, University of California, Davis, United States 1992–1994: Teaching Associate, Department of Technology, Professional University of Chongqing, Chongqing, China Education 1994-2000: M.S. & Ph.D., Chinese Academy of Medical Sciences (Peking Union Medical College), China Department: Institute of Medicinal Biotechnology Major: Molecular Biology & Medical Biochemistry Director:
Prof. Yuan Li, Chinese Academy of Medical Sciences
Prof. Ben Shen, University of California, Davis, United States
Thesis title: “Biosynthesis of the Enediyne Antitumor Antibiotic C-1027”
1988-1992: B.S., Sichuan University, China Department: Biotechnology Major: Microbiology 1988-1992: Student, First Middle School of Yibin, Sichuan, China Department: Biotechnology Major: Microbiology Honors and 2013: Distinguished Lectureship Award, Chemical Society of Japan (CSJ) 2013: Outstanding Academic Leader, Science and Technology Commission 2012: Excellent Postgraduate Tutor, Chinese Academy of Sciences (CAS) 2012:Leading Talent Award, Science and Technology Commission of 2011: Outstanding Instructor Award, Chinese Academy of Sciences (CAS) 2010: Senauer Faye Ann Wandt Young Biology Prize, Chinese 2009: Member of Excellence of “Hundred Talents Program”, CAS 2005: Distinguished Young Scholar, Chinese National Scientific Foundation
2005: Pujiang Scholar, Science and Technology Commission of Shanghai
2005: Rising-Star Scholar, STCSM Professional Associations Vice Chairman, Molecular Microbiology and Biological Engineering Committee, Chinese Society of Microbiology Member of Standing Committee, Enzyme engineering and Fermentation Engineering Committee, Chinese Medicine Biological Technology Association Member, Molecular Biology Committee, Chinese Society of Microbiology Member, Organic Chemistry Committee, Shanghai Chemical Industry Institute Member, 5th Editorial Board of “Chinese Journal of Organic Chemistry” Member, 8th Editorial Board of “Chinese Journal of Antibiotics” Selected Recent 1. Wang, S.; Zhou, S.; Liu, W., Opportunities and Challenges from Current Publications
Investigations into the Biosynthetic Logic of Nosiheptide-Represented Thiopeptide Antibiotics. Current Opinion in Chemical Biology 2013, invited 2. Zhang, Q.; Pang, B.; Ding, W.; Liu, W., Aromatic polyketides produced by
bacterial Iterative type I polyketide synthases. ACS Catalysis 2013, 3, 1439- 1447; 3. 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. 4. 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. 5. 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 2012, 135 (4), 1540-1548. 6. Zhang, Q.; Liu, W., Biosynthesis of thiopeptide antibiotics and their pathway
engineering. Natural Product Reports 2013, 30, 218-226. 7. 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. 8. 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. 9. 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. 10. 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. 11. 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. 12. 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. 13. 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. 14. 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. 15. 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. 16. 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. 17. Zhang, Q.; Liu, W., Complex biotransformations catalyzed by radical S-
adenosylmethionine enzymes. Journal of Biological Chemistry 2011, 286 (35), 30245-30252. 18. 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). 19. 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. 20. 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). 21. 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. 22. 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. 23. 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. 24. 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. 25. 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. 26. 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. 27. 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. 28. 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. 29. 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, 48,6770-6773; Recent advances in thiopeptide antibiotic biosynthesis. Nat. Prod. Rep. 2010, 27, 153-164). 30. 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). 31. 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. 32. 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. 33. 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. 34. 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. 35. 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. 36. 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). 37. 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). 38. 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. 39. 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. 40. 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. 41. 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. 42. 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. 43. 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. 44. 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. 45. 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. 46. 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. 47. 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. 48. 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. 49. 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. 50. 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. 51. 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). 52. 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). 53. 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.
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