High-Throughput Enantiopurity Measurement using Fluorescent Enantiomeric DNA Biosensors

在化学系化学测量和成像项目的支持下，犹他州大学的Jennifer Heemstra教授及其团队将开发新方法，以实现小分子对映体纯度的高通量分析。 近年来，酶作为传统催化剂的有前途的替代品，在实验室中指导立体选择性化学转化。 使用标准的分子生物学技术可以快速获得包含数百万种酶的文库，但是目前对酶立体选择性的评价仅限于每天数万个样品。 Heemstra教授和她的团队旨在通过开发和实施基于DNA的传感器来克服这一限制，这些传感器提供基于荧光的对映体纯度读数。 与目前可用的对映体纯度测量方法相比，使用基于荧光的读数将提高通量超过一个数量级。 该项目在教育方面的广泛影响包括培训研究生和本科生，设计新的化学生物学课程，鼓励妇女参与科学。 此外，本研究将为开发环境友好的大规模合成药物相关化合物的方法做出重大贡献，预计本研究将提供更快速，更有效的方法来测量小分子对映体纯度。 原则上，所开发的方法可以应用于化学和生物催化剂的测试和优化。 此外，预计新的立体选择性酶将被更快地发现，因为筛选目前代表了该过程中的瓶颈。 增加获得立体选择性酶的机会，反过来又将有助于采用更有效和环境友好的方法来生产药品和其他高价值化学品。 该项目还将为学生提供良好的培训，并扩大代表性不足的群体对科学的参与。

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.