Citation: Yu Peng, Yue Wang, Tian-Jiao Chen, Jing-Jing Chen, Jin-Ling Yang, Ting Gong, Ping Zhu. A fungal CYP from Beauveria bassiana with promiscuous steroid hydroxylation capabilities[J]. Chinese Chemical Letters, ;2024, 35(5): 108818. doi: 10.1016/j.cclet.2023.108818 shu

A fungal CYP from Beauveria bassiana with promiscuous steroid hydroxylation capabilities

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

gongting@imm.ac.cn

zhuping@imm.ac.cn

Received Date: 5 May 2023
Revised Date: 9 July 2023
Accepted Date: 14 July 2023
Available Online: 17 July 2023

Figures(5)

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 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, 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 promising biocatalyst for enriching the steroid structural and functional diversity, which also can be applied to biosynthesize valuable steroid drug intermediates.
- Fungal CYPs,
- Steroid hydroxylase,
- Beauveria bassiana,
- Promiscuous biocatalyst,
- Molecular dynamics
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