High-Throughput Enantiopurity Measurement using Fluorescent Enantiomeric DNA Biosensors

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With support from the Chemical Measurement and Imaging Program in the Division of Chemistry, Professor Jennifer Heemstra at University of Utah and her group will be developing new methods to enable high-throughput analysis of small-molecule enantiopurity. Enzymes have recently emerged as promising alternatives to traditional catalysts for directing stereoselective chemical transformations in the laboratory. Libraries containing millions of enzymes can be obtained rapidly using standard molecular biology techniques, but evaluation of enzyme stereoselectivity is currently limited to tens of thousands of samples per day. Professor Heemstra and her team aim to overcome this limitation through the development and implementation of DNA-based sensors that provide a fluorescence-based readout of enantiopurity. The use of a fluorescence-based readout will improve throughput by more than an order of magnitude compared with the currently available methods for enantiopurity measurement. The educational broader impacts of this project include the training of graduate and undergraduate students, the design of a new Chemical Biology course, and encouraging the participation of women in science. Additionally, this research will contribute significantly towards the development of environmentally friendly methods for the large-scale synthesis of pharmaceutically relevant compounds.This research is anticipated to provide faster and more efficient methods for measuring small-molecule enantiopurity. In principle, the methods developed could be applied towards the testing and optimization of both chemical and biological catalysts. Furthermore, it is expected that new stereoselective enzymes will be discovered more rapidly, as screening currently represents the bottleneck in this process. Improving access to stereoselective enzymes will in turn allow for the implementation of more efficient and environmentally benign methods for generating pharmaceuticals and other high-value chemicals. This project will also provide excellent training for students and broaden participation in science among underrepresented groups.