A fungal CYP from Beauveria bassiana with promiscuous steroid hydroxylation capabilities  

作　　者：Yu Peng Yue Wang Tian-Jiao Chen Jing-Jing Chen Jin-Ling Yang Ting Gong Ping Zhu 

机构地区：[1]State Key Laboratory of Bioactive Substance and Function of Natural Medicines,NHC Key Laboratory of Biosynthesis of Natural Products,CAMS Key Laboratory of Enzyme and Biocatalysis of Natural Drugs,Institute of Materia Medica,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100050,China

出　　处：《Chinese Chemical Letters》2024年第5期218-222,共5页中国化学快报（英文版）

基　　金：supported by the National Key Research and Development Program of China(Nos.2020YFA0908003 and 2018YFA0901900);CAMS Innovation Fund for Medical Sciences(No.CIFMS2021-I2M-1-029).

摘　　要：Hydroxylation of steroid core is critical to the synthesis of steroid drugs.Direct sp^(3) C-H hydroxylation is challenging through chemical catalysis,alternatively,fungal biotransformation offers a possible solution to this problem.However,mining and metabolic engineering of cytochrome P450 monooxygenases(CYPs)is usually regarded as a more eco-friendly and efficient strategy.Herein,we report the mining and identification of a new steroid CYP(CYP68BE1)from Beauveria bassiana by transcriptomics,heterologous expression,in vivo and in vitro functional characterization.The catalytic promiscuity of CYP68BE1 was explored,and CYP68BE1 showed promiscuously and catalytically versatile,which is qualified for monohydroxylation on C11α,C1α,C6βand dihydroxylation on C1β,11αand C6β,11αof six steroids,leading to the production of key steroid intermediates required in the industrial synthesis of some indispensable steroid drugs.Molecular dynamics simulations were performed,revealing the molecular basis of different binding orientations of CYP68BE1 with different substrates.The discovery of CYP68BE1 offers a promising biocatalyst for enriching the steroid structural and functional diversity,which also can be applied to biosynthesize valuable steroid drug intermediates.

关 键 词：Fungal CYPs Steroid hydroxylase Beauveria bassiana Promiscuous biocatalyst Molecular dynamics 

分 类 号：TQ460.1[化学工程—制药化工]