---

Education:

• B.Sc. 1982 Hangzhou University, China
• M.S. 1984 The Chinese Academy of Sciences
• Ph.D. 1991 Organic Chem/Biochem Oregon State University
• Postdoctoral 1995 University of Wisconsin-Madison

Overview

Ben Shen, Professor of Pharmaceutical Sciences and Charles M. Johnson Chair in Pharmacy, School of Pharmacy, and Professor of Chemistry, Department of Chemistry, received his B.Sc. degree in chemistry from Hangzhou University (1982), M.S. degree in chemistry from the Chinese Academy of Sciences (1984), and Ph.D. degree in organic chemistry/biochemistry from Oregon State University (1991). He held postdoctoral appointment at the University of Wisconsin-Madison (1991-95). Before joining the University of Wisconsin-Madison faculty in 2001, he was an Assistant Professor of Chemistry (1995-2001) and Associate Professor of Chemistry (2001-2) at the University of California, Davis. His current research interests are secondary metabolite biosynthesis in microorganisms, gene cloning and expression, enzyme reaction mechanisms, metabolic pathway engineering, combinatorial biosynthesis, and natural product drug discovery and development.

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 opportunities in both academia and pharmaceutical and biotechnology industry. Current projects include: (i) cloning and characterization of novel natural product biosynthetic gene clusters and machinery, (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.

Work-Related Interests/Research:

Secondary metabolite biosynthesis in microorganisms, gene cloning and expression, enzyme reaction mechanisms, metabolic pathway engineering, combinatorial biosynthesis, and natural product drug discovery and development.

Highlighted Publications:

• Galm, U.; Wendt-Pienkowski, E.; Wang, L.; George, N. P.; Oh, T.-J.; Yi, F.; Tao, M.; Coughlin, J. M; Shen, B. (2009) The biosynthetic gene cluster of zorbamycin, a member of the bleomycin family of antitumor antibiotics, from Streptomyces flavoviridis ATCC21892. Mol. BioSyst. 4:77-90.
• Beerman, T. A.; Gawron, L. S.; Shin, S.; Shen, B.; McHugh, M. M. (2009) C-1027, a radiomimetic enediyne anticancer drug, preferentially target hypoxic cells. Cancer Res. 69:593-598.
• Feng, Z,; Wang, L.; Rajski, S. R.; Xu, Z.; Coeffet-LeGal, M, F.; Shen, B. (2009) Engineered production of iso-migrastatin in heterologous hosts. Bioorg. Med. Chem. 17:2147-2159.
• Ju, J.; Rajski, S. R.; Lim, S.-K.; Seo, J.-W.; Peters, N. R.; Hoffmann, F. M.; Shen, B. (2009) Lactimidomycin, iso-migrastatin and related glutarimide-containing 12-membered macrolides are extremely potent inhibitors of cell migration. J. Am. Chem. Soc. 131:1370-1371.
• Lin, S.; Van Lanen, S. G.; Shen, B. (2009) A free-standing condensation enzyme catalyzing ester bond formation in C-1027 biosynthesis. Proc. Natl. Acad. Sci. USA 106:4183-4188.
• Rajski, S. R.; Shen, B. (2009) The role of evolution in the discovery of new drugs and chemicals. In ACS Symposium Series: Chemical Evolution II: From Origins of Life to Modern Society, Zaikowski, L.; Friedrich, J. M.; Seidel, S. R. Eds., ACS, Washington DC, in press.
• Horsman, G. P.; Van Lanen, S. G.; Shen, B. (2009) Iterative type I polyketide synthase for enediyne core biosynthesis. Methods in Enzymology 459:97-112.
• Jiang, H.; Rajski, S. R.; Shen, B. (2009) Tandem acyl carrier protein domains in polyunsaturated fatty acid synthases. Methods in Enzymology 459:79-96.
• Cheng, Y.-Q.; Coughlin, J. M.; Lim, S.-K.; Shen, B. (2009) Type I polyketide synthases that require discrete acyltransferases. Methods in Enzymology 459:165-186.
• Smanski, M. J.; Peterson, R. M.; Rajski, S. R.; Shen, B. (2009) Engineered Streptomyces platensis strains that overproduce antibiotics platensimycin and platencin. Antimicrob. Agents Chermother. 53:1299-13404.
• Li, W.; Luo, Y.; Ju, J.; Rajski, S. R. ; Osada, H. ; Shen, B. (2009) Characterization of the tautomycetin biosynthetic gene cluster from Streptomyces griseochromogenes provides new insight into dialkylmaleic anhydride biosynthesis. J. Nat. Prod. 72:450-459.
• Liao, R.; Duan, L.; Lei, C.; Pan, H.; Ding, Y.; Zhang, Q.; Chen, D.; Shen, B.; Yu, Y.; Liu, W. (2009) Thiopeptide biosynthesis featuring ribosomally synthesized precursor peptides and conserved posttranslational modifications. Chem. Biol. 16:141-147.
• Wang, L.; Tao, M.; Wendt-Pienkowski, E.; Galm, U.; Coughlin, J. M.; Shen, B. (2009) Functional characterization of tlmK unveiling unstable carbinolamide intermediates in the tallysomycin biosynthetic pathway. J. Biol. Chem. 284:8256-8264.
• Huang, S.-X.; Zhao, L.-X.; Tang, S.-K.; Jiang, C.-L.; Duan, Y.; Shen, B. (2009) Erythronolides H and I, new erythromycin congeners from a halophilic actinomycete Actinopolyspora sp. YIM90600. Org. Lett. 11:1353-1356.
• Ju, J.; Li, W.; Yuan, Q.; Peters, N. ; Hoffmann, F.M., Rajski, S.R.; Osada, H.; Shen, B. (2009) Functional characterization of ttmM unveils new tautomycin analogs and insight into tautomycin biosynthesis and activity. Org. Lett. 11:1639-1642.
• Adler, J.; Cook, M.; Luo, Y.; Pitt, S.; Ju, J.; Li, W.; Shen, B.; Kunnimalaiyaan, M.; Chen, H. (2009) Tautomycetin and tautomycin suppress the growth of medullary thyroid cancer cells via inhibition of GSK-3b. Mol. Cancer Therap. 8:914-920.
• Liu, T.; Huang, Y.; Shen, B. (2009) The bifunctional acyltransferase/decarboxylase LnmK as the missing link for β-alkylation in polyketide biosynthesis. J. Am. Chem. Soc. 132:6900-6901.
• Pinchot, S. N.; Adler, J. T.; Luo, Y.; Ju, J.; Li, W.; Shen, B.; Kunnimalaiyaan, M.; Chen, H. (2009) Tautomycin suppress the growth and neuroendocrine hormone markers in carcinoid cells through activation of the raf-1 pathway. Am. J. Surg. 197:313-319.
• Chen, Y.; Wendt-Pienkowski, E.; Rajski, S. R.; Shen, B. (2009) In vivo investigation of the roles of FdmM and FdmM1 in fredericamycin biosynthesis unveiling a new family of oxygenases. J. Biol. Chem. 284:24735-24743.
• Yu, Y.; Duan, L.; Zhang, Q.; Liao, R.; Ding, Y.; Pan, H.; Wendt-Pienkowski, E.; Tang, G.; Shen, B.; Liu, W. (2009) Nosiheptide biosynthesis featuring a unique indole side ring formation on the characteristic thiopeptide framework. ACS Chem. Biol. 4:Epub (doi:10.1021/cb900133x).
• Van Lanen, S. G.; Lin, S.; Horsman, G. P.; Shen, B. (2009) Characterization of SgcE6, the flavin reductase component supporting FAD-dependent halogenation and hydroxylation in the biosynthesis of the enediyne antitumor antibiotic C-1027. FEMS Microbiol Lett. 300:237-241.
• Lim, S.-K.; Ju, J.; Zazopoulos, E.; Jiang, H.; Seo, J.-W.; Chen, Y.; Feng, Z.; Rajski, S. R.; Farnet, C. M.; Shen, B. (2009) iso-Migrastatin, migrastatin, and dorrigocin production in Streptomyces platensis NRRL18993 is governed by a single biosynthetic machinery featuring an acyltransferase-less type I polyketide synthase. J. Biol. Chem. 284:29746-29756.
• Cooke, H. A.; Guenther, E. L.; Luo, Y.; Shen, B.; Bruner, S. G. (2009) Molecular basis of substrate promiscuity for the SAM-dependent NcsB1 O-methyltransferase involved in the biosynthesis of the enediyne antitumor antibiotic neocarzinostatin? Biochemistry 48:9590-9598.
• Lin, S.; Horsman, G. P.; Chen, Y.; Li, W.; Shen, B. (2009) Characterization of the SgcF epoxide hydrolase supporting a (R)-vicinal diol intermediate for enediyne antitumor antibiotic C-1027 biosynthesis. J. Am. Chem. Soc. 131:Epub (doi:10.102/ja901242s).
• Tao, M.; Wang, L.; Wendt-Pienkowski, E.; Zhang, N.; Yang, D.; Galm, U.; Coughlin, J. M.; Xu, Z.; Shen, B. (2009) Functional characterization of tlmH in Streptoalloteichus hindustanus E465-94 ATCC31158 unveiling new insight into tallysomycin biosynthesis and affording a new bleomycin analog. Mol. BioSyst. 4:Epub (DOI:10.1039/B918106G).