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

ACS Chemical Biology
Filippo FiorentiniAndrea Mattevi

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.

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Citations

Jul 1, 2016·Drug Metabolism Reviews·Thomas A BaillieS Cyrus Khojasteh
Sep 30, 2016·Expert Opinion on Drug Metabolism & Toxicology·Ian R Phillips, Elizabeth A Shephard
May 19, 2017·The Journal of Biological Chemistry·Ryan RossnerScott F Leiser
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Jun 7, 2020·Applied Microbiology and Biotechnology·Carolin MüggeDirk Tischler
Oct 4, 2019·Free Radical Biology & Medicine·Gianluca CatucciSheila J Sadeghi
Mar 18, 2020·Journal of Medicinal Chemistry·Benjamin M JohnsonNicholas A Meanwell
May 5, 2021·Drug Metabolism Reviews·Nikhilesh V DhuriaJasleen K Sodhi
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Jan 13, 2018·Chemical Reviews·Elvira RomeroAndrea Mattevi
Aug 8, 2017·ACS Chemical Biology·Filippo FiorentiniAndrea Mattevi

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