Enhancing ferryl accumulation in H 2 O 2 -dependent cytochrome P450s

A facile strategy is presented to enhance the accumulation of ferryl (iron(IV)-oxo) species in H O dependent cytochrome P450s (CYPs) of the CYP152 family. We report the characterization of a highly chemoselective CYP decarboxylase from Staphylococcus aureus (OleT ) that is soluble at high concentrat...

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Bibliographic Details
Published in:Journal of inorganic biochemistry 2024-03, Vol.252, p.112458
Main Authors: Amaya, Jose A, Manley, Olivia M, Bian, Julia C, Rutland, Cooper D, Leschinsky, Nicholas, Ratigan, Steven C, Makris, Thomas M
Format: Article
Language:English
Subjects:
Cytochrome P-450 Enzyme System - chemistry
Fatty Acids - chemistry
Hydrogen Peroxide
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Summary:A facile strategy is presented to enhance the accumulation of ferryl (iron(IV)-oxo) species in H O dependent cytochrome P450s (CYPs) of the CYP152 family. We report the characterization of a highly chemoselective CYP decarboxylase from Staphylococcus aureus (OleT ) that is soluble at high concentrations. Examination of OleT Compound I (CpdI) accumulation with a variety of fatty acid substrates reveals a dependence on resting spin-state equilibrium. Alteration of this equilibrium through targeted mutagenesis of the proximal pocket favors the high-spin form, and as a result, enhances Cpd-I accumulation to nearly stoichiometric yields.
ISSN:1873-3344
DOI:10.1016/j.jinorgbio.2023.112458