A Unique P450 Peroxygenase System Facilitated by a Dual-Functional Small Molecule: Concept, Application, and Perspective

Cytochrome P450 monooxygenases (P450s) are promising versatile oxidative biocatalysts. However, the practical use of P450s in vitro is limited by their dependence on the co-enzyme NAD(P)H and the complex electron transport system. Using H O simplifies the catalytic cycle of P450s; however, most P450...

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Bibliographic Details
Published in:Antioxidants 2022-03, Vol.11 (3), p.529
Main Authors: Di, Siyu, Fan, Shengxian, Jiang, Fengjie, Cong, Zhiqi
Format: Article
Language:English
Subjects:
Alkanes
Amino acids
Biocatalysts
Catalysis
Catalysts
Computational chemistry
Crystal structure
Cytochrome
Cytochrome P450
cytochrome P450 monooxygenase
Efficiency
Electron transport
Engineering
Enzymes
Epoxidation
Hydrogen peroxide
Hydroxylation
Mimicry
Mutagenesis
NAD
Oxidation
Peroxidase
peroxygenase
Protein engineering
Proteins
Review
Sulfoxidation
Thioanisole
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Summary:Cytochrome P450 monooxygenases (P450s) are promising versatile oxidative biocatalysts. However, the practical use of P450s in vitro is limited by their dependence on the co-enzyme NAD(P)H and the complex electron transport system. Using H O simplifies the catalytic cycle of P450s; however, most P450s are inactive in the presence of H O . By mimicking the molecular structure and catalytic mechanism of natural peroxygenases and peroxidases, an artificial P450 peroxygenase system has been designed with the assistance of a dual-functional small molecule (DFSM). DFSMs, such as -(ω-imidazolyl fatty acyl)-l-amino acids, use an acyl amino acid as an anchoring group to bind the enzyme, and the imidazolyl group at the other end functions as a general acid-base catalyst in the activation of H O . In combination with protein engineering, the DFSM-facilitated P450 peroxygenase system has been used in various oxidation reactions of non-native substrates, such as alkene epoxidation, thioanisole sulfoxidation, and alkanes and aromatic hydroxylation, which showed unique activities and selectivity. Moreover, the DFSM-facilitated P450 peroxygenase system can switch to the peroxidase mode by mechanism-guided protein engineering. In this short review, the design, mechanism, evolution, application, and perspective of these novel non-natural P450 peroxygenases for the oxidation of non-native substrates are discussed.
ISSN:2076-3921
2076-3921
DOI:10.3390/antiox11030529