Structure-Guided Regulation in the Enantioselectivity of an Epoxide Hydrolase to Produce Enantiomeric Monosubstituted Epoxides and Vicinal Diols via Kinetic Resolution

作者：Die Hu, Bo-Chun Hu, Xiaodong Hou, Dong Zhang, Yuqing Lei, Yijian Rao, Minchen Wu · 发表于：Organic Letters · 年份：2022 · DOI：10.1021/acs.orglett.1c04348 · 被引用次数：15 · 研究领域：Enzyme Catalysis and Immobilization、Cyclopropane Reaction Mechanisms、Synthesis and Catalytic Reactions

Structure-guided microtuning of an Aspergillus usamii epoxide hydrolase was executed. One mutant, A214C/A250I, displayed a 12.6-fold enhanced enantiomeric ratio ( E = 202) toward rac -styrene oxide, achieving its nearly perfect kinetic resolution at 0.8 M in pure water or 1.6 M in n -hexanol/water. Several other beneficial mutants also displayed significantly improved E values, offering promising biocatalysts to access 19 structurally diverse chiral monosubstituted epoxides (97.1 – ≥ 99% ee s ) and vicinal diols (56.2–98.0% ee p ) with high yields.