The stereoselective oxidation of para-substituted benzenes by a cytochrome P450 biocatalyst
Date
2021
Authors
Chao, R.
Lau, I.
Coleman, T.
Churchman, L.R.
Child, S.A.
Lee, J.H.Z.
Bruning, J.B.
De Voss, J.J.
Bell, S.G.
Editors
Advisors
Journal Title
Journal ISSN
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Type:
Journal article
Citation
Chemistry - A European Journal, 2021; 27(59):14765-14777
Statement of Responsibility
Rebecca R. Chao, Ian C.-K. Lau, Tom Coleman, Luke R. Churchman, Stella A. Child, Joel H.Z. Lee, John B. Bruning, James J. De Voss, and Stephen G. Bell
Conference Name
Abstract
The serine 244 to aspartate (S244D) variant of the cytochrome P450 enzyme CYP199A4 was used to expand its substrate range beyond benzoic acids. Substrates, in which the carboxylate group of the benzoic acid moiety is replaced were oxidised with high activity by the S244D mutant (product formation rates >60 nmol.(nmol-CYP)⁻¹.min⁻¹) and with total turnover numbers of up to 20,000. Ethyl α-hydroxylation was more rapid than methyl oxidation, styrene epoxidation and S-oxidation. The S244D mutant catalysed the ethyl hydroxylation, epoxidation and sulfoxidation reactions with an excess of one stereoisomer (in some instances up to >98 %). The crystal structure of 4-methoxybenzoic acid-bound CYP199A4 S244D showed that the active site architecture and the substrate orientation were similar to that of the WT enzyme. Overall, this work demonstrates that CYP199A4 can catalyse the stereoselective hydroxylation, epoxidation or sulfoxidation of substituted benzene substrates under mild conditions resulting in more sustainable transformations using this heme monooxygenase enzyme.
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First published: 04 August 2021
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© 2021 Wiley-VCH GmbH