Dual‐Functional Small Molecules for Generating an Efficient Cytochrome P450BM3 Peroxygenase |
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Authors: | Nana Ma Zhifeng Chen Jie Chen Dr. Jingfei Chen Dr. Cong Wang Prof. Dr. Haifeng Zhou Prof. Dr. Lishan Yao Dr. Osami Shoji Prof. Dr. Yoshihito Watanabe Prof. Dr. Zhiqi Cong |
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Affiliation: | 1. CAS Key Laboratory of Biofuels and Shandong Provincial Key Laboratory of Synthetic Biology, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, Shandong, China;2. University of Chinese Academy of Sciences, Beijing, China;3. Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Sciences, China Three Gorges University, Yichang, Hubei, China;4. Department of Chemistry, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya, Japan |
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Abstract: | We report a unique strategy for the development of a H2O2‐dependent cytochrome P450BM3 system, which catalyzes the monooxygenation of non‐native substrates with the assistance of dual‐functional small molecules (DFSMs), such as N‐(ω‐imidazolyl fatty acyl)‐l ‐amino acids. The acyl amino acid group of DFSM is responsible for bounding to enzyme as an anchoring group, while the imidazolyl group plays the role of general acid–base catalyst in the activation of H2O2. This system affords the best peroxygenase activity for the epoxidation of styrene, sulfoxidation of thioanisole, and hydroxylation of ethylbenzene among those P450–H2O2 system previously reported. This work provides the first example of the activation of the normally H2O2‐inert P450s through the introduction of an exogenous small molecule. This approach improves the potential use of P450s in organic synthesis as it avoids the expensive consumption of the reduced nicotinamide cofactor NAD(P)H and its dependent electron transport system. This introduces a promising approach for exploiting enzyme activity and function based on direct chemical intervention in the catalytic process. |
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Keywords: | enzyme catalysis cytochromes oxidoreductase peroxygenase protein engineering |
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