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Ben Shen, Ph.D.

Professor
Vice Chair, Department of Chemistry
Director, The Natural Products Library Initiative at TSRI
Department of Chemistry
Florida Campus
Laboratory Website
shenb@scripps.edu
(561) 228-2456

Scripps Research Joint Appointments

Professor, Department of Molecular Therapeutics
Professor, Worm Institute for Research and Medicine (WIRM)
Faculty, Graduate Program

Research Focus

Natural Product Biosynthesis, Engineering, and Drug Discovery.  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 (http://www.scripps.edu/shen/).

The Natural Products Library Initiative (NPLI) at TSRI.  Natural products are significantly underrepresented in current small molecule libraries.  The current NPL at TSRI consists of: (i) purified natural products with fully assigned structures, (b) MPLC (on C-18 semipreparative column) fractions, and (c) crude extracts.  The NPL is presented in 384-well format with all materials dissolved in DMSO (1 mM for pure compounds and 50 mg/mL for fractions and extracts), compatible with most of the HTS platforms.  The NPL at TSRI currently available for screening includes: (a) 5,000 strains, (b) 500 pure natural products, (c) 2,200 MPLC fractions, and (d) 8,000 crude extracts.  The NPL grows at the rate of 100 strains/month and crude extracts, MPLC fractions, and pure natural products derived thereof.  The NPL provides an unprecedented molecular diversity to screen emerging targets for drug leads, and selected members of the NPL serves as outstanding small molecule probes to interrogate biology (http://www.scripps.edu/shen/NPLI/npliattsri.html).

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
2014-, Vice Chair, Department of Chemistry, 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
2015, Promega Biotechnology Research Award, American Society for Microbiology

2002-, Member, Editorial Board of J. Ind. Microbiol. Biotechnol.
2003-, Member, Editorial Advisory Board of J. Nat. Prod.
2005-, Member, Editorial Board of Curr. Bioactive Compds.
2005-, Member, Advisory Board of Mol. BioSyst.
2006-, Member, Editorial Board of Recent Patents on Anticancer Drug Discovery
2007-, Associate Editor, Acta Microbiologica Sinica
2009-, Member, Editorial Board of J. Antibiot.
2011, Guest Co-Editor, J. Antibiot. January issue in memory of C. Richard Hutchinson
2012, Guest Co-Editor, Curr. Opinion Chem. Biol. April issue on Biocatalysis and Biotransformation

Selected References

211. Dong, L.-B.; Rudolf, J. R.; Shen, B. (2016) Antibacterial sulfur-containing platensimycin and platencin congeners from Streptomyces platensis SB12029. Bioorg. Med. Chem. (http://dx.doi.org/10.1016/j.bmc.2016.04.026).

210. Li, W.; Li, X.; Huang, T.; Teng, Q.; Crnovcic, I.; Rader, C.; Shen, B. (2016) Engineered production of cancer targeting peptide (CTP)-containing C-1027 in Streptomyces globisporus and biological evaluation. Bioorg. Med. Chem. (http://dx.doi.org/10.1015/j.bmc.2016.04.017).

209. Shi, J.; Pan, J.; Liu, L.; Yang, D.; Lu, S.; Zhu, X.; Shen, B.; Duan, Y.; Huang, Y. (2016) Titer improvement of pilot-scale production of platensimycin from Streptomyces platensis SB12026. J. Ind. Microbiol. Biotechnol. in press.

208. Zhang, B.; Yang, D.; Yan, Y.; Pan, G.; Xiang, W.; Shen, B. (2016) Overproduction of lactimidomycin by cross-overexpression of genes encoding Streptomyces antibiotic regulatory proteins. Appl. Microbiol. Biotechnol. 100:2267-2277.

207. Smanski, M. J.; Zhou, H.; Claesen, J.; Shen, B.; Fischbach, M. A.; Voigt, C. A. (2016) Synthetic biology to access and expand nature's chemical diversity. Nat. Rev. Microbiol. 14:135-149.

206. Rudolf, J. D.; Yan, X.; Shen, B. (2016) Genome neighborhood network reveals insights into enediyne biosynthesis and facilitates prediction and prioritization for discovery. J. Ind. Microbiol. Biotechnol. 43:261-276.

205. Shen, B. (2015) A New Golden Age of natural products drug discovery. Cell. 163:1297-1300.

204. Rudolf, J. D.; Bigelow, L.; Chang, C.; Cuff, M. E.; Lohman, J.R.; Chang, C.-Y.; Ma, M.; Yang, D.; Clancy, S.; Babnigg, G.; Joachimiak, A.; Phillips, G.N. Jr.; Shen, B. (2015) Crystal structure of the zorbamycin-binding protein ZbmA, the primary self-resistance element in Streptomyces flavoviridis ATCC21892. Biochemistry 54:6842-6851.

203. Lohman, J.R.; Ma, M.; Osipiuk, J.; Nocek, B.; Kim, Y.; Chang, C.; Cuff, M.; Mack, J.; Bigelow, L.; Li, H.; Endres, M.; Babnigg, G.; Joachimiak, A.; Phillips, G.N. Jr.; Shen, B. (2015) Structural and evolutionary relationships of "AT-less" type I polyketide synthase ketosynthases. Proc. Natl. Acad. Sci. U.S.A. 112:12693-12698.

202. Ma, M.; Rateb, M.; Teng, Q.; Yang, D.; Rudolf, J.; Zhu, X.; Huang, Y.; Zhao, L.-X.; Jiang, Y.; Li, X.; Rader, C.; Duan, Y.; Shen, B. (2015) Angucyclines and angucyclinones from Streptomyces sp. CB01913 featuring C-ring cleavage and expansion. J. Nat. Prod. 78:2471-2480.

201. Medema, M. H.; et al.; Glockner, F. O. (2015) Minimum information about a biosynthetic gene cluster. Nat. Chem. Biol. 11:625-631.

200. Ma, M.; Lohman, J. R.; Liu, T.; Shen, B. (2015) C-S bond cleavage by a polyketide synthase domain. Proc. Natl. Acad. Sci. U.S.A. 112:10359-10364.

199. Rudolf, J. D.; Dong, L.-B.; Huang, T.; Shen, B. (2015) A genetically amenable platensimycin- and platencin-overproducer as a platform for biosynthetic explorations: a showcase of PtmO4, a long-chain acyl-CoA dehydrogenase. Mol. BioSyst. 11:2717-2726.

198. Liu, T.; Ma, M.; Ge, H.-M.; Yang, C.; Cleveland, J.; Shen, B. (2015) Synthesis and evaluation of 8,4'-dideshydroxy-leinamycin revealing new insights into the structure-activity relationship of the anticancer natural product leinamycin. Bioorg. Med. Chem. Lett. 25:4899-4902.

197. Huang, S.-X.; Yun, B.-S.; Ma, M.; Basu, H. S.; Church, D. R.; Ingenhorst, G.; Huang, Y.; Yang, D.; Lohman, J. R.; Tang, G.-L.; Ju, J.; Liu, T.; Wilding, G.; Shen, B. (2015) Leinamyicn E1 acting as an anticancer prodrug activated by reactive oxygen species. Proc. Natl. Acad. Sci. U.S.A. 112:8278-8283.

196. Yang, Z.; Cao, S.; Martens, C. A.; Xie, Z.; Ma, M.; Shen, B.; Moss, B (2015) Deciphering poxvirus gene expression by RNA sequencing and ribosome profiling. J. Viology 89:6874-6886.

195. Rateb, M. E.; Yang, D.; Vodanovic-Jankovic, S.; Yu, Z.; Kron, M. A.; Shen, B. (2015) Adipostatins A-D from Streptomyces sp. 4875 inhibiting Brugia malayi asparaginyl-tRNA synthetase and killing adult Brugia malayi parasites. J. Antibiot. 68:540-542.

194. Gao, X.; Wan, J.; Liu, B.; Ma, M.; Shen, B.; Qian, S.-B. (2015) Quantitative profiling of initiating ribosomes in vivo. Nat. Methods 12, 147-153.

193. Shen, B.; Hindra; Yan, X.; Huang, T.; Ge, H.; Yang, D.; Teng, Q.; Rudolf, J. D.; Lohman, J. R. (2015) Enediynes: exploration of microbial genomics to discover new anticancer drug leads. Bioorg. Med. Chem. Lett. 25:9-15.

See Shen Laboratory website for complete list of publications (http://www.scripps.edu/shen/researchoverview/publications.html).

See MyBibliography for complete list of publications (

http://www.ncbi.nlm.nih.gov/sites/myncbi/ben.shen.1/bibliography/42110543/public/?sort=date&direction=ascending)

Google Scholar Citations (http://scholar.google.com/citations?hl=en&user=LNnZEd4AAAAJ ).

Links

The Natural Products Library Initiative (NPLI) at TSRI