文献类型：期刊文献

英文题名：A Baeyer-Villiger monooxygenase from Cupriavidus basilensis catalyzes asymmetric synthesis of (R)-lansoprazole and other pharmaco-sulfoxides

作者：Liu, Feng[1,2];Shou, Chao[1,2];Geng, Qiang[1,2];Zhao, Chen[1,2];Xu, Jianhe[1,2];Yu, Huilei[1,2]

机构：[1]East China Univ Sci & Technol, Shanghai Collaborat Innovat Ctr Biomfg, State Key Lab Bioreactor Engn, 130 Meilong Rd, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Sch Biotechnol, 130 Meilong Rd, Shanghai 200237, Peoples R China

年份：2021

卷号：105

期号：8

起止页码：3169

外文期刊名：APPLIED MICROBIOLOGY AND BIOTECHNOLOGY

收录：;EI(收录号：20211410162958);WOS:【SCI-EXPANDED(收录号:WOS:000634651600001)】；

基金：This work was financially supported by the National Key Research and Development Program of China (2019YFA09005000 and 2018YFC1706200), the National Natural Science Foundation of China (21536004, 21922804, and 21871085), and the Fundamental Research Funds for the Central Universities (22221818014).

语种：英文

外文关键词：Baeyer-Villiger monooxygenase; asymmetric sulfoxidation; (R)-lansoprazole; proton pump inhibitor

摘要：Biocatalytic synthesis of pharmaco-chiral sulfoxides has gained interest in recent years for its environmental friendliness. However, only a few natural biocatalysts can be used for the efficient synthesis of pharmaco-sulfoxides, including (R)-lansoprazole, a chiral proton pump inhibitor used to treat gastrointestinal diseases. In this study, the sequence of BoBVMO (Baeyer-Villiger monooxygenase from Bradyrhizobium oligotrophicum) was used as a probe to identify BVMOs via genomic mining for the highly efficient synthesis of (R)-lansoprazole and other pharmaco-sulfoxides. After virtual sequence filtering, target gene cloning, heterologous expression, and activity screening for lansoprazole sulfide (LPS) monooxygenation, seven new BVMOs were identified among more than 10,000 homologous BVMOs. According to the conserved sequence and phylogenetic tree analysis, these discovered enzymes belong to the family of type I BVMOs and the ethionamide monooxygenase subtype. Among them, CbBVMO, Baeyer-Villiger monooxygenase from Cupriavidus basilensis, showed the highest efficiency and excellent enantioselectivity for converting LPS into (R)-lansoprazole. Moreover, CbBVMO showed a wide substrate spectrum toward other bulky prazole-family sulfides. The results indicate that CbBVMO is a potential enzyme for extending the application of BVMOs in pharmaceutical industry.