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New Reagents for Asymmetric Organic Synthesis from Engineered Cells

$415,000FY2002MPSNSF

University Of Florida, Gainesville FL

Investigators

Abstract

The objectives of this work are two fold. Professor Stewart first proposes to use metabolically active but nongrowing E. coli cells to effect stereoselective organic functional group reduction reactions. E. coli cells will first be engineered to produce yeast reductases with desirable properties then quantities of the desired cells will be grown and used to effect syntheses of enantiomerically enriched, biologically relevant targets. The principal investigator will then investigate NADPH-dependent enzyme reactions again using nongrowing E. coli cells with the aim of developing whole cells capable of effecting either oxidation or reduction reactions depending on the amount of NAD/NADPH present. With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Dr. Jon D. Stewart of the Department of Chemistry at the University of Florida. Dr. Stewart will work on the development of E. coli cells capable of catalyzing a number of chemical reactions. This group will explore stereoselective reduction reactions using enzymes contained in these whole cells. These reduction reactions produce molecules which are chiral (have two nonsuperimposable mirror images) and make only one of the two possible forms (a single enantiomer). Development of this family of reactions is one of the most important problems facing the pharmaceutical industry today. When developed, Dr. Stewart's work could be applied to the environmentally friendly syntheses of a number of biologically active molecules. Students trained during the course of this work will gain skills needed by the pharmaceutical industry which now produces a number of single enantiomer compounds.

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