Yuqiu Lan, Chenghua Zhang, Chunping Tang, Yang Ye, Rui Zhang, Xiang Sheng, Cangsong Liao
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引用次数: 0
Abstract
Aldolases are powerful C−C bond-forming enzymes for asymmetric organic synthesis because of their supreme stereoselectivity, compatibility with diverse electrophiles and nucleophiles, and promising scalability. Stereodivergent engineering of aldolases to tune the selectivity for the synthesis of stereoisomers of chiral molecules is highly desirable but has rarely been reported. Herein we report the semirational engineering of the decarboxylative aldolase UstD with a focused rational iterative site-specific mutagenesis (FRISM) strategy to perform a C−C bond-forming reaction with dione electrophiles. The variant obtained from a small mutant library showed divergent regioselectivity and diastereoselectivity compared to the wild-type enzyme, resulting in the production of 30 cyclic imino acids with stereocenters at the α and γ positions. Molecular dynamics simulation and kinetic data revealed the basis of selectivity.
期刊介绍:
Angewandte Chemie, a journal of the German Chemical Society (GDCh), maintains a leading position among scholarly journals in general chemistry with an impressive Impact Factor of 16.6 (2022 Journal Citation Reports, Clarivate, 2023). Published weekly in a reader-friendly format, it features new articles almost every day. Established in 1887, Angewandte Chemie is a prominent chemistry journal, offering a dynamic blend of Review-type articles, Highlights, Communications, and Research Articles on a weekly basis, making it unique in the field.