Directory | Contact | Careers | Intranet | Home

Scripps Research Joint Appointments

Professor, Department of Molecular Therapeutics
Faculty, Kellogg School of Science and Technology
Professor, Worm Institute for Research and Medicine (WIRM)
Faculty, Kellogg School of Science and Technology

Research Focus

Microorganisms produce a large variety of biologically active substances representing a vast diversity of fascinating molecular architecture not available in any other systems. Our research centers on the chemistry, biochemistry and genetics of the biosynthesis of these secondary metabolites. Blending organic chemistry, biochemistry, and molecular biology, we take a multidisciplinary approach to study the secondary metabolism by asking the following questions: what reactions are available in nature, what are the enzymatic mechanisms of these reactions, how are these reactions linked to produce complex structures, what are the regulatory mechanisms of these pathways, and, ultimately, how can we manipulate nature's biosynthetic machinery for the discovery and development of new drugs. Members of our group gain broad training spanning organic chemistry, biochemistry, microbiology and molecular biology, a qualification that is becoming essential for the modern bioorganic chemists who seek career opportunity in both academia and pharmaceutical and biotechnology industry.

Current research projects include: (i) cloning and characterization of novel natural product biosynthetic gene clusters and machineries, (ii) discovery and elucidation of novel enzymes, biochemistry, and mechanism of catalysis, (iii) engineering of natural product structure diversity by combinatorial biosynthesis methods for drug discovery and development, (iv) expression of natural product biosynthetic gene clusters in heterologous hosts for natural product production and development of new strategies for combinatorial biosynthesis, and (v) microbial natural product isolation and structural elucidation for anticancer and antiinfective drug discovery.

Education

Ph.D., Organic Chemistry and Biochemistry, Oregon State University, Corvallis, OR, 1991
M.S., Chemistry, The Chinese Academy of Sciences, China, 1984
B.S., Chemistry, Hangzhou University, China, 1982

Professional Experience

1991-95, Postdoctoral Research Associate, School of Pharmacy, UW-Madison, WI
1995-01, Assistant Professor, Department of Chemistry, University of California, Davis, CA
2001-03, Associate Professor, School of Pharmacy and Department of Chemistry, UW-Madison, WI
2004-10, Professor, School of Pharmacy and Department of Chemistry, UW-Madison, WI
2004-10, Charles M. Johnson Distinguished Chair, School of Pharmacy, UW-Madison, WI
2005-10, Principal Investigator, NCI UW National Cooperative Drug Discovery Group, Madison, WI
2011-, Professor, Departments of Chemistry and Molecular Therapeutics, TSRI, Jupiter, FL
2011-, Director, The Natural Products Library Initiative at TSRI, TSRI, Jupiter, FL

Awards & Professional Activities

1996-01, FIRST Award, NIH
1997-00, Searle Scholar, Searle Scholars Program
1998-03, CAREER Award, NSF
2000, Matt Suffness Award, American Society of Pharmacognosy
2001-06, Independent Scientist Award, NIH
2002, Jack L. Beal Award, American Society of Pharmacognosy
2011, Fellow, American Academy of Microbiology
2011, Fellow, American Association for the Advancement of Science

2002-, Member, Editorial Board of J. Ind. Microbiol. Biotechnol.
2002-, Member, Editorial Advisory Board of J. Nat. Prod.
2005-, Member, Editorial Board of Current Bioactive Compounds
2005-, Member, Advisory Board of Molecular BioSystems
2006-, Member, Editorial Board of Recent Patents on Anticancer Drug Discovery
2007-, Associate Editor, Acta Microbiologica Sinica
2009-, Member, Editorial Board of Journal of Antibiotics

Selected References

Shen, B. Editorial for the special issue of The Journal of Antibiotics dedicated to the late Professor C Richard Hutchinson. J. Antibiot. 2011, 64, 3-5.

Yu, Z.; Zhao, L.-X.; Jiang, C.-L.; Duan, Y.; Wong, L.; Carver, K. C.; Schuler, L. A.; Shen, B. Bafilomycins produced by an endophytic actinomycete Streptomyces sp. YIM56209. J. Antibiot. 2011, 64, 159-162.

Huang, S.-X.; Yu, Z.; Robert, F., Zhao, L.-X.; Jiang, Y.; Duan, Y.; Pelletier, J., Shen, B. Cycloheximide and congeners as inhibitors of eukaryotic protein synthesis from endophytic actinomycetes Streptomyces sps. YIM56132 and YIM56141. J. Antibiot. 2011, 64, 164-166.

Huang, Y.; Huang, S.-X.; Ju, J.; Tang, G.; Liu, T.; Shen, B. Functional characterization of the lnmKLM genes unveiling key intermediates for b-alkylation in leinamycin biosynthesis. Org. Lett. 2011, 13, 498-501.

Liu, S.; Yu, Z.; Yu, X.; Huang, S.-X., Luo, Y.; Wu, L.; Yang, Z.; Wang, L.; Gunawan, A.; Chan, R.J.; Shen, B.; Zhang, Z.-Y. SHP2 is a target of the immunosuppressant tautomycetin. Chem. Biol. 2011, 18, 101-110.

Zhang, Q.; Li, Y.; Chen, D.; Yu, Y.; Duan, L.; Shen, B.; Liu, W. Radical-mediated enzymatic carbon chain fragmentation-recombination. Nat. Chem. Biol. 2011, 7, 154-160.

Yang, D.; Zhu, X.; Wu, X.; Feng, Z.; Huang, L.; Shen, B.; Zhang, Y. Titer improvement of iso-migrastatin in the selected heterologous Streptomyces hosts and related analysis of mRNA expression by quantitative RT-PCR. Appl. Microbiol. Biotechnol. 2011, 89, 1709-1719.

Galm, U.; Wendt-Pienkowski, E.; Wang, L.; Huang, S.; Unsin, C.; Tao, M.; Coughlin, J. M.; Shen, B. Comparative analysis of the biosynthetic Gene cluster and pathways for three structurall related antitumor antibiotics bleomycin, tallysomycin and zorbamycin. J. Nat. Prod. 2011, 74, 526-539.

Chen, Y.; Yin, M.; Horsman, G. P.; Shen, B. Improvement of the enediyne antitumor antibiotic C-1027 production by manipulating its biosynthetic pathway regulation in Streptomyces globisporus. J. Nat. Prod. 2011, 74, 420-424.

Yu, Z.; Vodanovic-Jankovic, S.; Ledeboer, N.; Huang, S.-X.; Rajski, S. R.; Kron, M.; Shen, B. Tirandamycins from Streptomyces sp. 17944 inhibiting the parasite Brugia malayi asparagine tRNA synthetase. Org. Lett. 2011, 13, 2034-2037.

Yin, M.; Lu, T.; Zhao, L.-X.; Chen, Y.; Huang, S.-X.; Lohman, J. R.; Xu, L.-H.; Jiang, C.-L.; Shen, B. The missing C-17 O-methyltransferase in geldanamycin biosynthesis. Org. Lett.  2011, 13, 3726-3729.

Smanski, M. J.; Yu, Z.; Casper, J.; Lin, S.; Peterson, R. M.; Chen, Y.; Wendt-Pienkowski, E.; Rajski, S. R.; Shen, B. Dedicated ent-kaurene and ent-atiserene synthases for platensimycin and platencin biosynthesis. Proc. Natl. Acad. Sci. USA 2011, 108, 13498-13503.

Zhao, L.-X.; Huang, S.-X.; Tang, S.-K.; Jiang, C.-L.; Duan Y.; Beutler, J. A.; Henrich, C. J.; McMahon, J. B.; Schmid, T.; Blees, J. S.; Colburn, N. H.; Rajski, S. R.; Shen, B. Actinopolysporins A-C and tubercidin as a Pdcd4 stabilizer from the halophilic actinomycete Actinopolyspora erythraea YIM 90600. J. Nat. Prod.  2011, 108, 74, 1990-1995.

Van Lanen, S.G.; Shen, B. "Combinatorial Biosynthesis of Anticancer Natural Products" in Antitumor Agents from Natural Products, 2nd Ed., Kingston, D.G.I.; Cragg, G.M.; Newman, D.J. eds., CRC Press Boca Raton, 2012, pp667-694.

Huang, S.-X.; Wang, X.-J.; Yan, Y.; Wang, J.-D.; Zhang, J.; Liu, C.-X.; Xiang, W.-S.; Shen, B. Neaumycin - a new macrolide from Streptomyces sp. NEAU-x211. Org. Lett. 2012, 14, 1254-1257.

Yang, D.; Li, W.; Huang, S.-X.; Shen, B. Functional characterization of ttnI completing the tailoring steps for tautomycetin biosynthesis in Streptomyces griseochromogenes. Org. Lett. 2012, 14, 1302-1305.

Shen, B.; Thorson, B. Expanding nature's chemical repertoire through metabolic engineering and biocatalysis. Curr. Opinion Chem. Biol. 2012, 16, 99-100.

Smanski, M. J.; Peterson, R. M.; Huang, S.-X.; Shen, B. Bacterial diterpene synthases: new opportunities for mechanistic enzymology and engineered biosynthesis. Curr. Opinion Chem. Biol. 2012, 16, 132-141.

Lin, S.; Huang, T.; Horsman, G. P.; Huang, S.-X.; Guo, X.; Shen, B. Specificity of the ester bond-forming condensation enzyme SgcC5 in C-1027 biosynthesis. Org. Lett. 2012, 14, 2300-2303.

Smanski, M. J.; Qu, X.; Liu, W.; Shen, B. "Biosynthesis of pharmaceutical natural products and their pathway engineering", Chapter 5 in Organic Chemistry - Breakthroughs and Perspectives. Ding, K.; Dai, L. eds.; Wiley VCH, 2012, in press.

Unsin, C. E.-M.; Rajski, S. R.; Shen, B. "The Role of Genetic Engineering in Natural Produc-based Anticancer Drug Discovery" in Natural Products and Cancer Drug Discovery, Koehn, F. E. ed., Springer, New York, NY, 2012, in press.

Smanski, M. J.; Peterson, R. M.; Shen, B. Platensimycin and platencin biosynthesis in Streptomyces platensis showcasing discovery and characterization of novel diterpene synthases. Methods Enzymol. 2012, 458, in press.

Lohman J. R.; Shen, B. 4-Methylideneimidazole-5-one-containing aminomutases in enediyne biosynthesis. Methods Enzymol. 2012, 459, in press.

Lin, S.; Huang, T.; Shen, B. Tailoring enzymes acting on carrier protein-tethered substrates in natural product biosynthesis. Methods Enzymol. 2012, 459, in press.