title: Biocatalytic Characterization of Human FMO5: Unearthing Baeyer-Villiger Reactions in Humans.
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 FMO5 (along its physiological role) has long remained unexplored. In this study, we demonstrate the atypical in vitro activity of human FMO5 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 FMO5 apart from all characterized Baeyer-Villiger mono-oxygenases so far. These findings open new perspectives in human oxidative metabolism.
authors.affiliation: Department of Biology and Biotechnology, University of Pavia , via Ferrata 9, 27100 Pavia, Italy.|Austrian Centre of Industrial Biotechnology, c/o Institute of Molecular Biotechnology, Graz University of Technology , Petersgasse 14, 8010 Graz, Austria.
authors.forename: Filippo
authors.initials: F
authors.lastname: Fiorentini
authors.affiliation: Austrian Centre of Industrial Biotechnology, c/o Institute of Molecular Biotechnology, Graz University of Technology , Petersgasse 14, 8010 Graz, Austria.
authors.forename: Martina
authors.initials: M
authors.lastname: Geier
authors.affiliation: Department of Biology and Biotechnology, University of Pavia , via Ferrata 9, 27100 Pavia, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Binda
authors.affiliation: Austrian Centre of Industrial Biotechnology, c/o Institute of Molecular Biotechnology, Graz University of Technology , Petersgasse 14, 8010 Graz, Austria.
authors.forename: Margit
authors.initials: M
authors.lastname: Winkler
authors.affiliation: Department of Chemistry, University of Graz , Heinrichstrasse 28, 8010 Graz, Austria.
authors.forename: Kurt
authors.initials: K
authors.lastname: Faber
authors.affiliation: Department of Chemistry, University of Graz , Heinrichstrasse 28, 8010 Graz, Austria.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Hall
authors.affiliation: Department of Biology and Biotechnology, University of Pavia , via Ferrata 9, 27100 Pavia, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Mattevi
mesh_terms: D055162:Biocatalysis; D006801:Humans; D010105:Oxygenases / Q000378:metabolism*
chemical_list: D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming)