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Chemistry

Faculty

Ben Shen, Ph.D.

Co-chair
Professor
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 Medicine
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) 5,500 strains, (b) 500 pure natural products, (c) 4,600 MPLC fractions, and (d) 10,173 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
2011-16, Professor, Departments of Chemistry and Molecular Therapeutics, TSRI, Jupiter, FL
2014-16, Vice Chair, Department of Chemistry, TSRI, Jupiter, FL
2011-, Director, The Natural Products Library Initiative at TSRI, TSRI, Jupiter, FL
2017-, Professor and Co-Chair, Department of Chemistry, TSRI, Jupiter, FL
2017-, Professor, Department of Molecular Medicine, 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

2002-16, 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
2017-, Editor, J. Ind. Microbiol. Biotechnol.

Selected References

243. Chen, J.-J.; Rateb, M. E.; Love, M. S.; Xu, Z.; Yang, D.; Zhu, X.; Huang, Y.; Zhao, L.-X.; Jiang, Y.; Duan, Y.; McNamara, C. W.; Shen, B. (2018) Herbicidins from Streptomyces sp. CB01388 showing anti-cryptosporidium activity. J. Nat. Prod. 81:in press.

242. Qiu, L.; Tian, K.; Wen Z.; Deng, Y.; Kang, D.; Liang, H.; Zhu, X.; Shen, B.; Duan, Y.; Huang, Y. (2018) Biomimetic stereoselective sulfa-Michael addition leads to potent platensimycin and platencin sulfur analogues against methicillin-resistant Staphylococcus aureus. J. Nat. Prod. 81:in press.

241. Guo, X.; Crnovcic, I.; Lohman, J. R.; Papinski, M.; Horsman, G. P.; Bechthold, A.; Shen, B. (2018) PokMT1 from the polyketomycin biosynthetic machinery of Streptomyces diastatochromogenes Tü6028 belongs to the emerging family of C-methyltransferases that act on CoA-activated aromatic substrates. Biochemistry 57:1003-1011.

240. Liu, L.; Pan, J.; Wang, Z.; Yan, X.; Yang, D.; Zhu, X.; Shen, B.; Duan, Y.; Huang, Y. (2018) Ribosome engineering and fermentation optimization leads to overproduction of tiancimycin A, a new enediyne natural product from Streptomyces sp. CB03234. J. Ind. Microbiol. Biotechnol. 45:141-151.

239. Yan, X.; Hindra; Ge, H.; Yang, D.; Huang, T.; Crnovcic, I.; Chang, C.-Y.; Fang, S.; Annaval, T.; Zhu, X.; Huang, Y.; Zhao, L.-X.; Jiang, Y.; Duan, Y.; Shen, B. (2018) Discovery of alternative producers of the enediyne antitumor antibiotic C-1027 with high titers. J. Nat. Prod. 81:(DOI:10.102/acs.jnatprod.7b01013).

238. Zhu, X.; Kong, J.; Yang, H.; Huang, R.; Huang, Y; Yang, D.; Shen, B.; Duan, Y. (2018) Strain improvement by combined UV mutagenesis and ribosome engineering and subsequent fermentation optimization for enhanced 6′-deoxy-bleomycin Z production. Appl. Microbiol. Biotechnol. 102:1651-1661.

237. Yang, D.; Hindra, Dong, L.-B.; Crnovcic, I.; Shen, B. (2018) Engineered production and evaluation of 6′-deoxy-tallysomycin H-1 revealing new insights into the structure-activity relationship of the anticancer drug bleomycin. J. Antibiot. 71:97-103.

236. Nejad, M. I.; Yang, D.; Shen, B.; Gates, K. S. (2018) Oxidative activation of leinamycin E1 triggers alkylation of guanine residues in double-stranded DNA. Chem. Comm. 54:256-259.

235. Pan, G.; Xu, Z.; Guo, Z.; Hindra; Ma, M.; Yang, D.; Zhou, H.; Gansemans, Y.; Zhu, X.; Huang, Y.; Zhao, L.-X.; Jiang, Y.; Cheng, J.; Van Nieuwerburgh, F.; Suh, J.-W.; Duan, Y.; Shen, B. (2017) Discovery of the leinamycin family of natural products by mining actinobacterial genomes. Proc. Natl. Acad. Sci. USA 114:E11131-E11140.

234. Yan, X.; Chen, J.-J.; Adhikari, A.; Yang, D.; Crnovcic, I.; Wang, N.; Chang, C.-Y.; Rader, C.; Shen, B. (2017) Genome mining of Micromonospora yangpuensis DSM 45577 as a producer of an anthraquinone-fused enediyne. Org. Lett. 19:6192-6195.

233. Annaval, T.; Rudolf, J. D.; Chang, C.-Y.; Lohman, J. R.; Kim, Y.; Bigelow, L.; Jedrzejczak, R.; Babnigg, G.; Joachimiak, A.; Phillips, G. N. Jr.; Shen, B. (2017) Crystal structure of the thioesterase SgcE10 supporting common polyene intermediates in 9- and 10-membered enediyne core biosynthesis. ACS Omega 2:5159-5169.

232. Rudolf, J. D.; Chang, C.-Y.; Ma, M.; Shen, B. (2017) Cytochromes P450 for natural product biosynthesis in Streptomyces: sequence, structure, and function. Nat. Prod. Rep. 34:1141-1172.

231. Zhang, B.; Xu, Z.; Teng, Q.; Pan, G.; Ma, M.; Shen, B. (2017) A Long-range acting dehydratase domain as the missing link for the C17-dehydration in iso-migrastatin biosynthesis. Angew Chem. Int. Ed. 56:7247-7251.

230. Falzone, M.; Crespo, E.; Jones, K.; Khan, G.; Korn, V.; Patel, A.; Patel, M.; Patel, K.; Perkins, C.; Siddiqui, S.; Stenger, A.; Yu, E.; Gelber, M.; Scheffler, R.; Nayda, V.; Ravin, A.; Komal, R.; Rudolf, J.; Shen, B.; Gullo, V.; Demain, A. (2017) Nutritional control of antibiotic production by Streptomyces platensis MA7327: Importance of L-aspartic acid. J. Antibiot. 70:828-831.

229. Hindra; Yang, D.; Dong, L.-B.; Teng, Q.; Huang, T.; Ge, H.; Crnovčić, I.; Shen, B. (2017) Genome mining of Streptomyces mobaraensis DSM40847 as a bleomycin producer providing a biotechnology platform to engineer designer bleomycin analogues. Org. Lett. 19:1386-1389.

228. Dong, L.-B.; Rudolf, J. D.; Lin, L.; Ruiz, C.; Cameron, M. D.; Shen, B. (2017) In vivo instability of platensimycin and platencin: Synthesis and biological evaluation of urea- and carbamate-platensimycin. Bioorg. Med. Chem. 25:1990-1996.

227. Chen, J. K.; Yang, D.; Shen, B.; Murray, V. (2017) Bleomycin analogues preferentially cleave at the transcription start sites of actively transcribed genes in human cells. Int. J. Biochem. Cell Biol. 85:56-65.

226. Yang, D.; Rateb, M. E.; Wang, N.; Shen, B. (2017) Competition and co-regulation of spirotoamide and tautomycetin biosynthesis in Streptomyces griseochromogenes and isolation and structural elucidation of spirotoamide C and D. J. Antibiot. 70:710-740.

225. Rudolf, J. D.; Crnovcic, I.; Shen, B. (2017) "Chapter 3, The Role of Combinatorial Biosynthesis in Natural Products Discovery" in Chemical Biology of Natural Products, Cragg, G.; Newman, D.; Grothaus, P. Eds, Taylor and Francis, pp87-125.

224. Rudolf, J. D.; Dong, L.-B.; Shen, B. (2017) Platensimycin and platencin: inspiration for chemistry, biology, enzymology, and medicine. Biochem. Pharmacol. 133:139-151.

223. Guo, Z.; Pan, G.; Xu, Z.; Yang, D.; Hindra, Zhu, X.; Huang, Y.; Zhao, L.-X.; Jiang, Y.; Duan, Y.; Shen, B. (2017) New isofuranonaphthoquinones and isoindolequinones from Streptomyces sp. CB01883. J. Antiboit. 70:414-422.

222. Ma, M.; Rateb, M.; Yang, D.; Rudolf, J.; Zhu, X.; Huang, Y.; Zhao, L.-X.; Jiang, Y.; Duan, Y.; Shen, B. (2017) Germicidins H-J from Streptomyces sp. CB00361. J. Antibiot. 70:200-203.

221. Qiu, L.; Tian, K.; Pan, J.; Jiang, L.; Yang, H.; Zhu, X.; Shen, B.; Duan, Y; Huang, Y. (2017) A facile semi-synthetic approach towards halogen-substituted aminobenzoic acid analogues of platensimycin. Tetrahedron, 73:771-775.

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