首页|A fungal CYP from Beauveria bassiana with promiscuous steroid hydroxylation capabilities
A fungal CYP from Beauveria bassiana with promiscuous steroid hydroxylation capabilities
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Hydroxylation of steroid core is critical to the synthesis of steroid drugs.Direct sp3 C-H hydroxylation is challenging through chemical catalysis,alternatively,fungal biotransformation offers a possible solu-tion 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 mono-hydroxylation on C11α,C1α,C6β and dihydroxylation on C1β,11α and C6β,11α of 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 promis-ing biocatalyst for enriching the steroid structural and functional diversity,which also can be applied to biosynthesize valuable steroid drug intermediates.
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
国家重点研发计划国家重点研发计划Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences
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