Flavin-containing mono-oxygenases are known as potent drug metabolizing enzymes, providing complementary functions to the well-investigated cytochrome P450 mono-oxygenases. While human FMO isoforms are typically involved in the oxidation of soft nucleophiles, the biocatalytic activity of human FMOS (along its physiological role) has long remained unexplored. In this study, we demonstrate the atypical in vitro activity of human FMOS as a Baeyer-Villiger mono-oxygenase on a broad range of substrates, revealing the first example to date of a human protein catalyzing such reactions. The isolated and purified protein was active on diverse carbonyl compounds, whereas soft nucleophiles were mostly non- or poorly reactive. The absence of the typical characteristic sequence motifs sets human FMOS apart from all characterized Baeyer-Villiger mono-oxygenases so far. These findings open new perspectives in human oxidative metabolism.

Biocatalytic Characterization of Human FMO5: Unearthing Baeyer-Villiger Reactions in Humans

FIORENTINI, FILIPPO
Methodology
;
BINDA, CLAUDIA
Methodology
;
MATTEVI, ANDREA
Conceptualization
2016-01-01

Abstract

Flavin-containing mono-oxygenases are known as potent drug metabolizing enzymes, providing complementary functions to the well-investigated cytochrome P450 mono-oxygenases. While human FMO isoforms are typically involved in the oxidation of soft nucleophiles, the biocatalytic activity of human FMOS (along its physiological role) has long remained unexplored. In this study, we demonstrate the atypical in vitro activity of human FMOS as a Baeyer-Villiger mono-oxygenase on a broad range of substrates, revealing the first example to date of a human protein catalyzing such reactions. The isolated and purified protein was active on diverse carbonyl compounds, whereas soft nucleophiles were mostly non- or poorly reactive. The absence of the typical characteristic sequence motifs sets human FMOS apart from all characterized Baeyer-Villiger mono-oxygenases so far. These findings open new perspectives in human oxidative metabolism.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11571/1122442
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