SusChEM: Small-Molecule Enantiopurity Measurement in Living Cells as a Method to Accelerate Biocatalyst Discovery

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The Chemical Measurement and Imaging program of the Chemistry Division of the National Science Foundation funds this project. Professor Jennifer Heemstra of the University of Utah is developing methods to rapidly assay reaction conditions for the selective production of small molecules. This research aids in the use of enzymes to catalyze key steps in the synthesis of therapeutics and other high value chemicals. The reactions currently used to generate these products often require metal-containing catalysts and organic solvents. The disposal of both catalyst and solvent pose an environmental hazard. In contrast, enzyme catalysts are environmentally benign, as the enzymes themselves are non-toxic, and they are used in water rather than organic solvents. The broader impacts of this research are demonstrated in multiple ways. This research provides training to high school, undergraduate, and graduate students. Also included is an outreach activity aimed at improving the retention of college women in STEM disciplines. The research has potential to benefit society by facilitating the discovery of new, environmentally benign methods for the synthesis of high-value chemicals such as small-molecule therapeutics.The overarching objectives of this proposal are to explore methods to rapidly generate DNA biosensors for small-molecule targets of interest and to deploy these sensors in living bacterial cells. Methods are developed to enable the selection of DNA biosensors for an enzymatically-produced small molecule that is a pharmaceutical intermediate. The proposed research explores the ability of fluorescent DNA biosensors to be transfected into bacterial cells and used to quantify the intracellular concentration of a target analyte.