(R)-兰索拉唑不对称合成中Baeyer-Villiger单加氧酶的筛选  

Screening of Baeyer-Villiger monooxygenases for asymmetric synthesis of(R)-lansoprazole

作　　者：李邱红 王乾韬 王慧婧 LI Qiuhong;WANG Qiantao;WANG Huijing(West China School of Pharmacy,Sichuan University,Chengdu,Sichuan,610041 P.R.China)

机构地区：[1]四川大学华西药学院,四川成都610041

出　　处：《华西药学杂志》2025年第1期6-9,共4页West China Journal of Pharmaceutical Sciences

基　　金：四川省科学技术厅项目(2022NSFSC0615)。

摘　　要：目的挖掘新的(R)-兰索拉唑不对称合成中的Baeyer-Villiger单加氧酶(BVMO)。方法在基因组数据库中挖掘、筛选得到6种候选BVMOs,将候选酶克隆至表达载体pET-28a(+)中,转化至大肠杆菌Escherichia coli BL21(DE3),筛选最佳诱导条件,获得可溶性蛋白。利用候选酶不对称催化合成(R)-兰索拉唑。结果挖掘得到的6种新酶中,PlBVMO、CSKBVMO、AbBVMO能够完成从底物兰索拉唑硫醚到(R)-兰索拉唑的不对称合成,其中,PlBVMO的收率达12.8%,对映体过量百分数(ee)>99%。结论挖掘、筛选新的BVMOs可为(R)-兰索拉唑类药物的生物合成提供新的方法与路线。OBJECTIVE To seek novel Baeyer-Villiger monooxygenases(BVMOs)for asymmetric synthesis of(R)-lansoprazole.METHODS Six BVMOs candidates were identified and screened from the genome database,cloned into the expression vector pET-28a(+),transpected into Escherichia coli BL21(DE3),and optimized for induction conditions to obtain soluble proteins.These candidate enzymes were utilized for the asymmetric synthesis of(R)-lansoprazole.RESULTS Among the six enzymes discovered,PlBVMO,CSKBVMO and AbBVMO were capable of successfully accomplishing the asymmetric synthesis of(R)-lansoprazole from the substrate lansoprazole sulfide.Notably,the PlBVMO exhibited a 12.8%yield with ee>99%.CONCLUSION The screening of novel BVMOs provides novel methods and pathways for the biosynthesis of(R)-lansoprazole and other pharmaceutically relevant compounds.

关 键 词：(R)-兰索拉唑 Baeyer-Villiger单加氧酶 基因挖掘 蛋白表达 蛋白电泳 酶催化 不对称合成 大肠杆菌 质子泵抑制剂 

分 类 号：R914[医药卫生—药物化学]