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

Filippo Fiorentini, Martina Geier, Claudia Binda, Margit Winkler, Kurt Faber, Mélanie Hall*, Andrea Matteiv*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Pages (from-to)1039-1048
JournalACS Chemical Biology
Issue number4
Publication statusPublished - 2016

Fields of Expertise

  • Human- & Biotechnology

Treatment code (Nähere Zuordnung)

  • Experimental
  • Basic - Fundamental (Grundlagenforschung)

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