Active Site Substitution A82W Improves the Regioselectivity of Steroid Hydroxylation by Cytochrome P450 BM3 Mutants As Rationalized by Spin Relaxation Nuclear Magnetic Resonance Studies

V. Rea, A.J. Kolkman, E.R. Vottero, E.J. Stronks, K.A. Ampt, M. Honing, N.P.E. Vermeulen, S.S. Wijmenga, J.N.M. Commandeur

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Cytochrome P450 BM3 from Bacillus megaterium is a monooxygenase with great potential for biotechnological applications. In this paper, we present engineered drug-metabolizing P450 BM3 mutants as a novel tool for regioselective hydroxylation of steroids at position 16β. In particular, we show that by replacing alanine at position 82 with a tryptophan in P450 BM3 mutants M01 and M11, the selectivity toward 16β-hydroxylation for both testosterone and norethisterone was strongly increased. The A82W mutation led to a ≤42-fold increase in V
Original languageEnglish
Pages (from-to)750-760
JournalBiochemistry
Volume51
Issue number3
DOIs
Publication statusPublished - 2012

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