Song Shucheng, Wang Chenyang, Bao Wenjing, Xu Zhenchuang, Wu Jian, Lin Liang, Zhao Yanchuan
State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, 345 Ling-Ling Road, Shanghai 200032, China.
State Key Laboratory of Fluorine and Nitrogen Chemistry and Advanced Materials and Shanghai Hongkong Joint Laboratory in Chemical Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Ling-Ling Road, Shanghai 200032, China.
ACS Cent Sci. 2025 Jun 3;11(7):1094-1102. doi: 10.1021/acscentsci.5c00498. eCollection 2025 Jul 23.
Biocatalysis is an essential tool for asymmetric synthesis, significantly enhancing the production of chiral molecules. As advancements in protein screening and engineering rapidly evolve, the demand for efficient, rapid chiral analysis methods has intensified. Addressing this need, we introduce a high-throughput F NMR-based assay that provides comprehensive insights into the enantioselectivity, stereopreference, and yields of biocatalytic reactions. This assay has been successfully applied to screen imine reductases, showcasing its efficacy in the directed evolution for synthesizing an intermediate of the anti-Parkinson drug, rotigotine. Our method offers substantial promise for propelling forward the fields of biocatalysis and synthetic biology by accelerating the assessment of stereochemical outcomes in biocatalytic processes.
生物催化是不对称合成的重要工具，可显著提高手性分子的产量。随着蛋白质筛选和工程技术的迅速发展，对高效、快速的手性分析方法的需求日益增加。为满足这一需求，我们引入了一种基于高通量¹⁹F NMR的分析方法，该方法可全面深入了解生物催化反应的对映选择性、立体偏好性和产率。该分析方法已成功应用于筛选亚胺还原酶，展示了其在合成抗帕金森药物罗替戈汀中间体的定向进化中的功效。我们的方法通过加速生物催化过程中立体化学结果的评估，为推动生物催化和合成生物学领域的发展提供了巨大的前景。
