Professor, Department of Molecular Medicine
Professor, Worm Institute for Research and Medicine (WIRM)
Faculty, Graduate Program
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) 450 pure natural products, (c) 3,400 MPLC fractions, and (d) 8,500 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).
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
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
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
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:in press (DOI:10.1016/j.bmc.2017.02.028).
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. in press (DOI:10.1016/j.biocel.2017.02.001).
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:in press (DOI:10.1038/ja.2017.13).
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, in press.
224. Rudolf, J. D.; Dong, L.-B.; Shen, B. (2017) Platensimycin and platencin: inspiration for chemistry, biology, enzymology, and medicine. Biochem. Pharmacol., in press (DOI:10.1016/j.bcp.2016.11.013).
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:(DOI:10.1038/ja.2016.122)
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.
220. Rudolf, J. D.; Dong, L.; Manoogian, K.; Shen, B. (2016) Biosynthetic origin of the ether ring in platensimycin. J. Am. Chem. Soc. 138:16711-16721.
219. Yan, X.; Ge, H.; Huang, T.; Hindra; Yang, D.; Teng, Q.; Crnovcic, I.; Li, X.; Rodulf, J. D.; Lohman, J. R.; Gansemans, Y.; Zhu, X.; Huang, Y.; Zhao, L.-X.; Jiang, Y.; Van Nieuwerburgh, F.; Rader, C.; Duan, Y.; Shen, B. (2016) Strain prioritization and genome mining for enediyne natural products. mBio. 7:e2104-16.
218. Chen, J. K.; Yang, D.; Shen, B.; Neilan, B. A.; Murry, V. (2016) Zorbamycin has a different DNA sequence selectivity compared with bleomycin and analogues. Bioorg. Med. Chem. 24:6094-6101.
217. Huang, Y.; Yang, D.; Pan, G.; Tang, G.-L.; Shen, B. (2016) Characterization of LnmO as a pathway-specific Crp/Fnr-type positive regulator for leinamycin biosynthesis in Streptomyces atroolivaceus and its application for titer improvement. Appl. Microbiol. Biotechnol. 100:10555-10562.
216. Dong, L.; Rudolf, J. D.; Shen, B. (2016) A mutasynthetic library of platensimycin and platencin analogues. Org. Lett. 18:4606-4609.
215. Chang, C.-Y.; Lohman, J. R.; Cao, H.; Tan, K.; Rudolf, J. D.; Ma, M.; Xu, W.; Bingman, C. A.; Ragothaman, M.; Bigelow, L.; Babnigg, G.; Yan, X.; Joachimiak, A.; Phillips, Jr., G. A.; Shen, B. (2016) Crystal structures of SgcE6 and SgcC, the two-component monooxygenase that catalyzes hydroxylation of a carrier protein-tethered substrate in biosynthesis of the enediyne antitumor antibiotic C-1027 in Streptomyces globisporus. Biochemistry 55:5142-5154.
214. Huang, Y.; Tang, G.-L.; Pan, G.; Chang, C.-Y.; Shen, B. (2016) Characterization of the ketosynthase and acyl carrier protein domains at the LnmI nonribosomal peptide synthetase-polyketide synthase interface for leinamycin biosynthesis. Org. Lett.18:4288-4291.
213. Rudolf, J. D.; Dong, L.-B.; Cao, H.; Hatzos-Skintges, C.; Osipiuk, J.; Endres, M.; Chang, C.-Y.; Ma, M.; Babnigg, G.; Joachimiak, A.; Phillips, Jr., G. N.; Shen, B. (2016) Structure of the ent-copalyl diphosphate synthase PtmT2 from Streptomyces platensis CB00739, a bacterial type II diterpene synthase. J. Am. Chem. Soc. 138:10905-10915.
212. Huang, T.; Chang, C.-Y.; Lohman, J. R.; Rudolf, J. D.; Kim, Y.; Chang, C.; Yang, D.; Ma, M.; Yan, X.; Crnovcic, I.; Bigelow, L.; Clancy, S.; Bingman, C. A.; Yennamalli, R. M.; Babnigg, G.; Joachimiak, A.; Phillips Jr., J. N.; Shen, B. (2016) Crystal structure of SgcJ, an NTF2-like superfamily protein involved in biosynthesis of the 9-membered enediyne antitumor antibiotic C-1027, J. Antibiot. 69:731-740.
211. Dong, L.-B.; Rudolf, J. R.; Shen, B. (2016) Antibacterial sulfur-containing platensimycin and platencin congeners from Streptomyces platensis SB12029. Bioorg. Med. Chem. 24:6348-6353.
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. 24:3884-3892.
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. 43:1027-1035.
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.
See Shen Laboratory website for complete list of publications (http://www.scripps.edu/shen/researchoverview/publications.html).
See MyBibliography for complete list of publications (
Google Scholar Citations (http://scholar.google.com/citations?hl=en&user=LNnZEd4AAAAJ ).