RUI: Interdisciplinary Collaboration to Expand Asymmetric Synthesis through Biocatalysis

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The overall goal of this project is to expand asymmetric synthesis techniques through biocatalysis. It includes three specific aims. Specific aim 1 involves the screening of a variety of prochiral substrates (ketones and oximes) against a library of engineered E. coli yeast reductases that have been characterized as excellent asymmetric reducing agents. Specific aim 2 involves the molecular modeling studies of 2,5-Diketo-D-gluconic acid reductase. In this reductase, the enzyme substrate interaction and its correlation with Si or Re face hydride transfer will be investigated. In specific aim 3, representative yeast reductases will be systematically mutated and the effects on the asymmetric reduction on known substrates will be determined. The goal of this aim is to attain a more accurate understanding of the enzyme-substrate complex and its role in determining enzyme stereoselectivity with the intention of improving asymmetric catalysts.With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Professor Brent Feske (Department of Chemistry and Physics), Professor Clifford Padgett (Department of Chemistry and Physics), and Professor Scott Mateer (Department of Biology) at Armstrong Atlantic State University. The combined research of these professors will investigate the use of enzymes to synthesize complex molecules with asymmetric centers. Successful development of this methodology will afford greener and more efficient routes to these molecules, which are needed in large numbers in the pharmaceutical industry.