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Chemistry

Faculty

Ben Shen, PhD

Professor
Professor
Director, Natural Products Discovery Center at Scripps Research
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 leverage a large microbial strain collection and develop enabling genome mining and synthetic biology technologies for natural product discovery and production, and 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/).

Natural Products Discovery Center at Scripps Research.  Natural products are significantly underrepresented in current small molecule libraries.  The current Natural Products Library (NPL) at Scripps Research's Natural Product Discovery Center 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 currently available for screening includes: (a) ~600 pure natural products, (b) ~53,500 MPLC fractions, (c) ~205,000 crude extracts.  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.  Central to the Natural Products Discovery Center is the large microbial strain collection, containing a total of 217,352 bacterial and fungal strains, of which 62,328 are actinobacteria, 14,465 other bacteria, 92,225 fungi, and 48,334 unidentified (bacteria or fungi).  Promising leads could therefore be produced in sufficient quantities by microbial fermentation for follow up studies and, ultimately, clinical development (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

1995-2001 Assist Prof, Dept of Chemistry, UC Davis, Davis, CA
2001-2002 Assoc Prof, Dept of Chemistry, UC Davis, Davis, CA
2001-2003 Assoc Prof, School of Pharmacy and Dept. of Chemistry, UW-Madison, Madison, WI
2004-2010 Prof, School of Pharmacy and Dept. of Chemistry, UW-Madison, Madison, WI
2004-2010 Charles M. Johnson Distinguished Chair, School of Pharmacy, UW-Madison, Madison, WI
2005-2010 Principal Investigator, NCI UW National Cooperative Drug Discovery Group, Madison, WI
2011-2016 Prof, Depts of Chemistry and Molecular Therapeutics, TSRI, Jupiter, FL
2011-2019 Director, The Natural Products Library Initiative at TSRI, TSRI, Jupiter, FL
2020- Director, The Natural Products Discovery Center at Scripps Research, TSRI, Jupiter, FL
2014-2016 Vice Chairman, Dept of Chemistry, TSRI, Jupiter, FL
2017- Prof, Depts of Chemistry and Molecular Medicine, TSRI, Jupiter, FL
2017-2021 Chair, Dept of Chemistry, Florida Campus, 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
2018, Charles Thom Award, Society of Industrial Microbiology and Biotechnology
2020, Outstanding Mentor Award, Society of Research Fellows, TSRI, Jupiter, FL
2021, Fellow, American Society of Pharmacognosy

2002-16, Member, Editorial Board of J. Ind. Microbiol. Biotechnol.
2003-17, Member, Editorial Advisory Board of J. Nat. Prod.
2005-17, Member, Advisory Board of Mol. BioSyst.
2006-, 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.
2021, Guest Co-Editor, J. Ind. Microbiol. Biotechnol. March-April special issue on Natural Product Discovery and Development in the Genomic Era: 2021

Selected References

293. Yang, D.; Ye, F.; Teijaro, C. N.; Hwang, D.; Annaval, T.; Adhikari, A.; Yan, X.; Gui, C.; Rader, C.; Shen, B. (2022) Functional characterization of cytochrome P450 hydroxylase YpmL in yangpumicin A biosynthesis and its application for anthraquinone-fused enediyne structural diversification. Org. Lett. 24:online

292. Ye, F.; Haniff, H. S.; Suresh, B. M.; Yang, D.; Zhang, P.; Crynen, G.; Teijaro, C. N.; Yan, W.; Abegg, D.; Adibekian, A.; Shen, B.; Disney, M. D. (2022) Rational approach to identify RNA targets of natural products enables identification of nocathiacin as am inhibitor of an oncogenic RNA. ACS Chem. Biol. 17:online

291. Kalkreutee, E; Shen, B. (2022) MIO-containing aminomutases for α- to β-amino acids. Trends Chem. 4:91-92.

290. Meng, S.; Steele, A. D.; Yan, W.; Pan, G.; Kalkreuter, E.; Liu, Y.-C.; Xu, Z.; Shen, B. (2021) Thiocysteine lyases as polyketide synthase domains installing hydropersulfide into natural products and a hydropersulfide methyltransferase. Nat. Commun. 12:5672.

289. Annaval, T.; Teijaro, C. N.; Adhikari, A.; Yan, X.; Chen, J.-J.; Crnovcic, I.; Yang, D.; Shen, B. (2021) Cytochrome P450 hydroxylase TnmL catalyzing sequential hydroxylation with an additional proof-reading reactivity in tiancimycin biosynthesis. ACS Chem. Biol. 16:1172-1178.

288. Hindra; Yang, D.; Luo, J.; Huang, T.; Yan, X.; Adhikari, A.; Teijaro, C. N.; Ge, H.; Shen, B. (2021) Submerged fermentation of Streptomyces uncialis providing a biotechnology platform for uncialamycin biosynthesis, engineering, and production. J. Ind. Microbiol. Biotechnol. 48:kuab025 (Special Issue on Natural Product Discovery and Development in Genomic Era).

287. Luo, J.; Yang, D.; Hindra; Adhikari, A.; Dong, L.-B.; Ye, F.; Yan, X.; Rader, C.; Shen, B. (2021) Discovery of ammosesters by mining the Streptomyces uncialis DCA2648 genome revealing new insight into ammosamide biosynthesis. J. Ind. Microbiol. Biotechnol. 48:kuab027 (Special Issue on Natural Product Discovery and Development in Genomic Era).

286. Shen, B.; Tang, T.; Baltz, R. H.; Ramon Gonzalez, R. (2021) Introduction to the special issue: “Natural Product Discovery and Development in the Genomic Era”. J. Ind. Microbiol. Biotechnol. 48:kuab030.

285. Li, Y.; Weng, X.; Deng, Y.; Pan, J.; Zhu, S.; Wen, Z.; Yuan, Y.; Li, S.; Shen, B.; Duan, Y.; Huang, Y. (2021) Semisynthesis and biological evaluation of platencin thioether derivatives: Dual FabF and FabH inhibitors against MRSA. ACS Med. Chem. Lett. 12:433-442.

284. Cao, M.; Zheng, C.-J.; Yang, D.; Kalkreuter, E.; Adhikari, A.; Liu, Y.-C.; Rateb, M. E.; Shen, B. (2021) Cryptic sulfur incorporation in thioangucycline biosynthesis. Angew. Chem. Intl. Eng. 60:7140-7147.

283. Adhikari, A.; Shen, B.; Rader, C. (2021) Challenges and opportunities to develop enediyne natural products as payloads for antibody-drug conjugates. Antib. Ther. 4:1-15.

282. Zheng, C.-J.; Kalkreuter, E.; Fan, B.-Y.; Liu, Y.-C.; Dong, L.-B.; Shen, B. (2021) PtmC catalyzes the final step of thioplatensimycin, thioplatencin, and thioplatensilin biosynthesis and expands the scope of arylamine N-acetyltransferases. ACS Chem. Biol. 16:96-105.

See Shen Laboratory website for complete list of publications (https://www.scripps.edu/shen/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

Natural Products Discovery Center at Scripps Research