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- Title
Regiodivergent and Enantioselective Hydroxylation of C−H bonds by Synergistic Use of Protein Engineering and Exogenous Dual‐Functional Small Molecules.
- Authors
Chen, Jie; Dong, Sheng; Fang, Wenhan; Jiang, Yiping; Chen, Zhifeng; Qin, Xiangquan; Wang, Cong; Zhou, Haifeng; Jin, Longyi; Feng, Yingang; Wang, Binju; Cong, Zhiqi
- Abstract
It is a great challenge to optionally access diverse hydroxylation products from a given substrate bearing multiple reaction sites of sp3 and sp2 C−H bonds. Herein, we report the highly selective divergent hydroxylation of alkylbenzenes by an engineered P450 peroxygenase driven by a dual‐functional small molecule (DFSM). Using combinations of various P450BM3 variants with DFSMs enabled access to more than half of all possible hydroxylated products from each substrate with excellent regioselectivity (up to >99 %), enantioselectivity (up to >99 % ee), and high total turnover numbers (up to 80963). Crystal structure analysis, molecular dynamic simulations, and theoretical calculations revealed that synergistic effects between exogenous DFSMs and the protein environment controlled regio‐ and enantioselectivity. This work has implications for exogenous‐molecule‐modulated enzymatic regiodivergent and enantioselective hydroxylation with potential applications in synthetic chemistry.
- Subjects
SMALL molecules; PROTEIN engineering; HYDROXYLATION; TURNOVER frequency (Catalysis); OXYGENASES; DYNAMIC simulation
- Publication
Angewandte Chemie, 2023, Vol 135, Issue 4, p1
- ISSN
0044-8249
- Publication type
Academic Journal
- DOI
10.1002/ange.202215088