Role of residue 87 in substrate selectivity and regioselectivity of drug-metabolizing cytochrome P450 CYP102A1 M11

E.R. Vottero, V. Rea, J. Lastdrager, M. Honing, N.P.E. Vermeulen, J.N.M. Commandeur

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

CYP102A1, originating from Bacillus megaterium, is a highly active enzyme which has attracted much attention because of its potential applicability as a biocatalyst for oxidative reactions. Previously we developed drug-metabolizing mutant CYP102A1 M11 by a combination of site-directed and random mutagenesis. CYP102A1 M11 contains eight mutations, when compared with wild-type CYP102A1, and is able to produce human-relevant metabolites of several pharmaceuticals. In this study, active-site residue 87 of drug-metabolizing mutant CYP102A1 M11 was mutated to all possible natural amino acids to investigate its role in substrate selectivity and regioselectivity. With alkoxyresorufins as substrates, large differences in substrate selectivities and coupling efficiencies were found, dependent on the nature of residue 87. For all combinations of alkoxyresorufins and mutants, extremely fast rates of NADPH oxidation were observed (up to 6,000 min
Original languageEnglish
Pages (from-to)899-912
Number of pages13
JournalJournal of Biological Inorganic Chemistry - JBIC
Volume16
Issue number6
DOIs
Publication statusPublished - 2011

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