Updated: February 16, 2015
James Thomas Payne
CBC Scholar: Class of 2013
PhD Candidate, Department of Chemistry, University of Chicago, Advisor: Jared Lewis
LEWIS LAB WEBPAGE
RESEARCH INTERESTS:
Halogenation is a ubiquitous and vital process in the development of pharmaceuticals, with an estimated quarter of all pharmaceuticals and agrochemicals being halogenated, and halogenation playing an integral role in the synthesis of many more. Despite this, the prevalent methods of halogenation suffer from a lack of site-selectivity and harsh reaction conditions, making the production of halogenated drug candidates difficult and environmentally unfriendly. To this end I have been working on the development of enzyme catalysts which perform site-selective halogenations of drug candidates in environmentally sustainable conditions. My preliminary work was focused on the expression of natural halogenating enzymes, particularly one called RebH, in E. coli and improving the expression of soluble RebH. Using this isolated material, the substrate scope of RebH was explored, and it was found to site-selectively halogenate a wide range of compounds, especially a variety of indole and naphthalene derivatives. Preparative scale enzymatic reactions on a number of these substrates were performed and the products isolated using techniques customary to synthetic chemists to prove the utility of RebH to the synthetic chemistry community. My work now is focused on the directed evolution of RebH to further enhance its activity and expand its substrate scope. Through the introduction of mutations in the genetic code for RebH, a variety of slightly altered RebH mutants are obtained and screened for changes in activity. Improved variants are characterized and further altered, thus recapitulating the process of evolution at a much accelerated pace in our laboratory. This research will both elucidate the role various mutations have in altering the activity of RebH and produce RebH variants useful for the development of novel drug candidates.
PUBLICATIONS:
Payne JT, Poor CB, Lewis JC. Directed Evolution of RebH for Site-Selective Halogenation of Large Biologically Active Molecules. Angew Chem Int Ed Engl. 2015 Feb 9. [Epub ahead of print] (PubMed)
Payne JT, Andorfer MC, Lewis JC. Regioselective Arene Halogenation using the FAD-Dependent Halogenase RebH. Angew Chem Int Ed Engl. 2013 May 10;52(20):5271-4. (PubMed)
Fleener CE, Payne JT, Chu YH, Chen CR, Gruendl RA. Massive Star Formation in NGC 2074. The Astronomical Journal 2010, 139, 158-167. (iop)
AWARDS, HONORS AND ACTIVITIES:
- Judge, Chicago Public Schools Student Science Fair, March 2013
- Chicago Biomedical Consortium (CBC) Scholar, 2013-2014
- Abbott Scholars Program, 2012
- NIH Chemistry-Biology Interface Training Fellowship, 2011-present