文献类型：期刊文献

英文题名：Enzymatic synthesis of pharmacologically relevant chiral sulfoxides by improved CbBVMO variants

作者：Zhao, Chen[1];Liu, Feng[1];Zhou, Min[1];Geng, Qiang[1];Yu, Hui-Lei[1]

机构：[1]East China Univ Sci & Technol, Shanghai Collaborat Innovat Ctr Biomfg, Sch Biotechnol, State Key Lab Bioreactor Engn, 130 Meilong Rd, Shanghai 200237, Peoples R China

年份：2023

卷号：59

期号：98

起止页码：14571

外文期刊名：CHEMICAL COMMUNICATIONS

收录：;EI(收录号：20234915185579);WOS:【SCI-EXPANDED(收录号:WOS:001107851700001)】；

基金：The work was financially supported by the National Natural Science Foundation of China (No. 32271540), the National Key Research and Development Program of China (Grants 2021YFC2102900 & 2019YFA0905000), and Program of Shanghai Academic Research Leader (21XD1400800)

语种：英文

摘要：Baeyer-Villiger monooxygenases (BVMOs) are able to catalyse the asymmetric oxidation of sulfides. This property has made them attractive catalysts for the synthesis of chiral sulfoxide drugs. Here, we have designed and synthesised an exhaustive combinatorial mutant library of the previously identified lansoprazole sulfide monooxygenase CbBVMOV1. From this synthetic combinatorial mutant library, the best mutant, CbBVMOV3, was selected with a specific activity of approximately 1 U mg(-1) for lansoprazole sulfoxides. We then optimised the reaction conditions of a two-phase system, achieving the enzymatic asymmetric synthesis of (R)-lansoprazole in a space-time yield of 213 g L-1 d(-1) and an enantiomeric excess of >99% (R) with no detectable by-products. In addition, CbBVMOV3 showed higher activity towards other prazole sulfides. These results indicate the potential application of CbBVMO in the chiral sulfoxide drug industry.