Biocatalytic enantioselective formation and ring-opening of oxetanes

作者：Xia Hua, Yuanfei Wang, Xiao Jin, Hong-Yin Yu, Huihui Wang, Yong‐Zheng Chen, Nan‐Wei Wan · 发表于：Nature Communications · 年份：2025 · DOI：10.1038/s41467-025-56463-z · 被引用次数：11 · 研究领域：Enzyme Catalysis and Immobilization、Chemical Synthesis and Analysis、Click Chemistry and Applications

Although biocatalysis offers complementary or alternative approaches to traditional synthetic methods, the limited range of available enzymatic reactions currently poses challenges in synthesizing a diverse array of desired compounds. Consequently, there is a significant demand for developing novel biocatalytic processes to enable reactions that were previously unattainable. Herein, we report the discovery and subsequent protein engineering of a unique halohydrin dehalogenase to develop a biocatalytic platform for enantioselective formation and ring-opening of oxetanes. This biocatalytic platform, exhibiting high efficiency, excellent enantioselectivity, and broad scopes, facilitates the preparative-scale synthesis of chiral oxetanes and a variety of chiral γ-substituted alcohols. Additionally, both the enantioselective oxetane formation and ring-opening processes are proven scalable for large-scale transformations at high substrate concentrations, and can be integrated efficiently in a one-pot, one-catalyst cascade system. This work expands the enzymatic toolbox for non-natural reactions and will promote further exploration of the catalytic repertoire of halohydrin dehalogenases in synthetic and pharmaceutical chemistry. Oxetane is a four-membered, oxygen-containing heterocyclic compound of importance in medicinal chemistry and drug development. Here, the authors report the discovery and subsequent protein engineering of a halohydrin dehalogenase, and develop a biocatalytic ...