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Education:

• B.A. 1986 Chemistry Augsburg College
• Ph.D. 1993 Organic Chemistry University of Minnesota
• Postdoctoral 1996 Bioorganic Chemistry University of California, Berkeley

Overview

Jon received his B.A. degree in chemistry (1986) from Augsburg College and a Ph.D. degree in organic chemistry (1993) from the University of Minnesota with Professor Hung-wen (Ben) Liu. He held a postdoctoral appointment as a Merck Postdoctoral Fellow of the Helen Hay Whitney Foundation (1993-1996) at the University of California, Berkeley with Professor Peter Schultz. From 1996-2001, Jon held appointments as an assistant member of the Memorial Sloan-Kettering Cancer Center and assistant professor of Sloan-Kettering Division, Joan and Sanford I. Weill Graduate School of Medical Sciences, Cornell University, during which he was named a Rita Allen Foundation Scholar (1998-2002) and Alfred P. Sloan Fellow (2000-2002). Professor Thorson joined the School of Pharmacy in the summer of 2001 and since moving to UW has been designated an American Society of Pharmacognosy Matt Suffness Awardee (2004) and a UW H. I. Romnes Fellow (2004). Professor Thorson was also instrumental in establishing the UW National Cooperative Drug Discovery Group, a NCI-funded consortium of UW-Madison scientists seeking to develop new anti-cancer drugs from natural products. His research interests include understanding and exploiting biosynthetic pathways and enzyme mechanisms, bioorganic and chemoselective ligation chemistries, enzyme engineering and evolution. Professor Thorson has also been credited with establishing the general area of natural product glycorandomization.

Historically, biology has provided unique lead compounds that serve as targets for the synthetic organic chemist interested in drug discovery. In contrast to a conventional synthetic chemistry approach, this laboratory strives to focus not upon the natural product as the objective, but upon the natural catalysts (enzymes) that construct therapeutically useful metabolites. Our detailed mechanistic understanding of the enzymes involved in these biosynthetic pathways, through the use of tools ranging from genetics to synthetic organic chemistry, provide the basis for their exploitation in engineering novel and highly effective therapeutic agents via combinatorial biosynthesis, biocatalysis and chemoselective ligation strategies (effectively 'enzymatic' chemical reactions). Efforts are under way in the arenas of antitumor (enediynes, angucyclines, anthracyclines, indolocarbazoles, alkaloids, flavanoids), antibiotic (macrolide, orthosomycin, coumarins and nonribosomal peptides), antifungal (polyenes) and antiviral (macrolide) biosynthesis.

Financial support for our work is currently provided in part by the National Institutes of Health (CA84374, AI52218 and GM70637), the Wisconsin Alumni Research Foundation (WARF), the UW Comprehensive Cancer Center and a National Cooperative Drug Discovery Group grant from NCI (U19 CA113297). We also gratefully acknowledge the Wyeth-Ayerst Laboratories Division of American Home Products, Ecopia Biosciences, Bristol-Myers Squibb Pharmaceutical Institute, Schering-Plough and members of the synthetic community for graciously providing materials.

Highlighted Publications:

• Goff RD, Thorson JS. Enhancing the divergent activities of betulinic acid via neoglycosylation. Org. Lett. 2009, 11, 461-464.
• McCoy J, Johnson HD, Singh S, Bingman CA, Lei I-K, Thorson JS, Phillips Jr GN. Structural characterization of CalO2: a putative orsellinic acid P450 oxidase in the calicheamicin biosynthetic pathway. Proteins 2009, 74, 50-60.
• Williams GJ, Thorson JS. Natural product glycosyltransferases: Properties and applications. Adv. Enzymol. Relat. Areas Mol. Biol.. 2009, 76, 55-119.
• Gantt RW, Goff RD, Williams GJ, Thorson JS. Probing the aglycon promiscuity of an engineered glycosyltransferase. Angew. Chem. Int. Ed. 2008, 47, 8889-8892.
• Williams GJ, Zhang C, Thorson JS. Expanding the promiscuity of a natural product glycosyltransferase by directed evolution. Nat. Chem. Biol. 2007, 3, 657-662.
• Zhang C, Griffith BR, Fu Q, Albermann C, Fu X, Lee IK, Li L, Thorson JS. Exploiting the reversibility of natural product glycosyltransferase-catalyzed reactions. Science 2006, 313, 1291-1294.
• Langenhan JM, Peters NR, Guzei IA, Hoffmann FM, Thorson JS. Enhancing the anti-cancer properties of cardiac glycosides via neoglycorandomization. Proc. Natl. Acad. Sci. USA 2005, 102, 12305-12310.
• Bililign T, Hyun C-G, Williams JS, Czisny AM, Thorson, JS. The hedamycin locus implicates a novel aromatic PKS priming mechanism. Chem. & Biol. 2004, 11, 959-969.
• Biggins JB, Onwueme KC, Thorson JS. The Mechanism of CalC: Resistance to enediyne antitumor antibiotics by self-sacrifice. Science 2003, 301, 1537-1541.
• Ahlert J, Shepard EM, Lomovskaya N, Zazopoulos E, Staffa A, Bachmann BO, Huang K, Yang X, Fonstein L, Czisny A, Whitwam RE, Farnet CM, Thorson JS. The calicheamicin gene cluster and its iterative type I enediyne PKS, Science 2002, 297, 1173-1176.
• Barton WA, Biggins JB, Lesniak J, Jeffrey PD, Jiang J, Rajashankar KR, Thorson JS, Nikolov DB. Structure, mechanism and active-site engineering of a nucleotidylyltransferase: The first step in the glycorandomization of natural product-based metabolites. Nat. Struct. Biol. 2001, 8, 2223-2226.
• Biggins JB, Prudent JR, Marshal DJ, Ruppen M, Thorson JS. A continuous assay for DNA cleavage: The application of 'break lights' to enediynes, iron-dependent agents and nucleases. Proc. Natl. Acad. Sci. USA 2000, 97, 13537-13542.