Hijacking Chemical Reactions of P450 Enzymes for Altered Chemical Reactions and Asymmetric Synthesis

Rajakumara, Eerappa and Saniya, Dubey and Bajaj, Priyanka and Rajeshwari, Rajanna and Giri, Jyotsnendu and Davari, Mehdi D. (2022) Hijacking Chemical Reactions of P450 Enzymes for Altered Chemical Reactions and Asymmetric Synthesis. International Journal of Molecular Sciences, 24 (1). p. 214. ISSN 1422-0067

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Cytochrome P450s are heme-containing enzymes capable of the oxidative transformation of a wide range of organic substrates. A protein scaffold that coordinates the heme iron, and the catalytic pocket residues, together, determine the reaction selectivity and regio- and stereo-selectivity of the P450 enzymes. Different substrates also affect the properties of P450s by binding to its catalytic pocket. Modulating the redox potential of the heme by substituting iron-coordinating residues changes the chemical reaction, the type of cofactor requirement, and the stereoselectivity of P450s. Around hundreds of P450s are experimentally characterized, therefore, a mechanistic understanding of the factors affecting their catalysis is increasingly vital in the age of synthetic biology and biotechnology. Engineering P450s can enable them to catalyze a variety of chemical reactions viz. oxygenation, peroxygenation, cyclopropanation, epoxidation, nitration, etc., to synthesize high-value chiral organic molecules with exceptionally high stereo- and regioselectivity and catalytic efficiency. This review will focus on recent studies of the mechanistic understandings of the modulation of heme redox potential in the engineered P450 variants, and the effect of small decoy molecules, dual function small molecules, and substrate mimetics on the type of chemical reaction and the catalytic cycle of the P450 enzymes.

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IITH Creators:
IITH CreatorsORCiD
Rajakumara, Eerappahttps://orcid.org/0000-0002-9341-0070
Giri, Jyotsnenduhttps://orcid.org/0000-0002-2313-4912
Item Type: Article
Uncontrolled Keywords: asymmetric synthesis; biocatalysis; cytochrome P450; enzyme engineering; prosthetic group; regioselectivity; stereoselectivity
Subjects: Biomedical Engineering > Molecular imaging
Divisions: Department of Biomedical Engineering
Department of Biotechnology
Depositing User: Mr Nigam Prasad Bisoyi
Date Deposited: 14 Aug 2023 11:27
Last Modified: 14 Aug 2023 11:27
URI: http://raiith.iith.ac.in/id/eprint/11532
Publisher URL: https://doi.org/10.3390/ijms24010214
OA policy: https://www.sherpa.ac.uk/id/publication/17518
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