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 and Transcriptome Mining for Discovery of Novel Microbial Natural
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 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 Honors and 2005: Distinguished Young Scholar Funded by CNSF
2005: Pujiang Scholar Funded by STCSM 2005: Rising-Star Scholar Funded by STCSM Professional Associations
Member of the 5th Editorial Board of “Chinese Journal of Organic Chemistry” Member of the 8th Editorial Board of “Chinese Journal of Antibiotics”
1. Smanski, M. J.; Qu, X. D.; Liu, W.*; Shen, B*. Biosynthesis of pharmaceutical natural Selected Recent
products and their pathway engineering. In Breakthoughs and Perspectives in Organic Publications 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,
2. Qu, X. D.; Lei, C.; Liu, W.*, Transcriptome mining of active biosynthetic pathways and
their associated products in Streptomyces flaveolus. Angewandte Chemie International Edition2011, doi: 10.1002/anie.201103085.
3. 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, doi: 10.1128/AEM.06034-11.
4. Zhang, Q.*; Liu, W.*, Complex biotransformations catalyzed by radical S-
adenosylmethionine enzymes. Journal of Biological Chemistry 2011, doi: 10.1074/jbc.R111.272690.
5. 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).
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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.
14. 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.
15. He, Q. L.; Jia, X. Y.; Tang, M. C.; Tian, Z. H.; Tang, G. L.; Liu, W.*, Dissection of Two
Acyl-Transfer Reactions Centered on Acyl-S-Carrier Protein Intermediates for Incorporating
Chembiochem 2009,10 (5), 813-819.
16. 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).
17. 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).
18. Liu, W.*; Yu, Y, Combinatorial Biosynthesis of pharmaceutical natural products.
manufacturing. In Biocatalysis for the Pharmaceutical Industry. Tao, J. H.; Lin, G. Q.; Liese, A. Eds. John Wiley & Sons Pte Ltd, 2009, pp229-245.
19. 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.
20. Fang, J.; Zhang, Y. P.; Huang, L. J.; Jia, X. Y.; Zhang, Q.; Zhang, X.; Tang, G. L.; 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.
21. 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.
22. Li, L.; Deng, W.; Song, J.; Ding, W.; Zhao, Q. F.; Peng, C.; Song, W. W.; Tang, G. L.*;
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.
23. 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).
24. Zhao, Q. F.; He, Q. L.; Ding, W.; Tang, M. C.; Kang, Q. J.; Yu, Y.; Deng, W.; Zhang,
Q.; Fang, J.; Tang, G. L.; 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: Nat. China
25. 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 Biotechnology2008, 136 (Supplement 1): S21-S21.
26. 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.
27. 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.
28. 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.
29. Jia, X. Y.; Tian, Z. H.; Shao, L.; Qu, X. D.; Zhao, Q. F.; Tang, J.; Tang, G. L.*; Liu, W.*, Genetic characterization of the chlorothricin gene cluster as a model for spirotetronate antibiotic biosynthesis. Chemistry & Biology 2006,13 (6), 575-585.
30. Shao, L.; Qu, X. D.; Jia, X. Y.; Zhao, Q. F.; Tian, Z. H.; Wang, M.; Tang, G. L.*; 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.
31. 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.
32. 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.
33. 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.
34. 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.
35. 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.
36. 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.
37. 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.
38. 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).
39. 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).
40. 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.
41. Wang, Z. L.; Zhao, Q. F.; Gao, S. H.; Chen, C. H.*; Liu, W.*, Construction of the New
Genetic Manipulation Method of Streptomyces lincolnensis and lmbQ Gene Function Verification2010, 11, 186-190.
42. Zhang, H.; Zhao, Q. F.; Yu, Y.; Lu, D. N.*; Liu, W.*, A PCR approach for specific
accession of the genes encoding the reduction domain of non-ribosomal peptide synthetase.2009, 34(3), 189-192.
43. Wang, Y.; Yu, Y.; Zhao, Q. F.; Kong, Y.*; Liu, W.*, Advance in Biosynthesis and
Combinatorial Biosynthesis of Natural Products.2008, 29(6), 275-282.
44. Liu, W.*, Progress of Biosynthesis of Enediyne Antitumor Antibiotics 2005, 27(3), 24-31.
45. Liu, W.*; Tang, G. L., Biosynthesis-Based Metabolic Engineering and Combinatorial
Biosynthesis2005, 25(1), 1-5.
46. Liu, W.; Li, Y.*, Study of biosynthesis gene cloning of novel antitumor antibiotic
Gibt es denn so etwas? Gestern kam die Polizei noch einmal, um das Dorf Al-Arakib zu zerstören und von der Erdoberfläche zu tilgen, zum 21. Mal in weniger als einem Jahr. Noch einmal wurden die schäbigen Hütten und Zelte zerstört und die Reste auf LKWs geladen und weggefahren, um ja nicht ein Spur zu hinterlassen. Und wieder kamen die Bulldozer des Jüdischen Nationalfond, um mit dem Vorbe
MEDICATION GUIDE Mifeprex® (MIF-eh-prex) Read this information carefully before taking Mifeprex* and misoprostol. It will help youunderstand how the treatment works. This MEDICATION GUIDE does not take the place oftalking with your health care provider (provider). What is Mifeprex? Mifeprex is used to end an early pregnancy. It blocks a hormone needed for your pregnancy to continue.