InterPro domain: IPR020946

Flavin-containing monooxygenases (FMOs) constitute a family of xenobiotic-metabolising enzymes [ 1 ]. Using an NADPH cofactor and FAD prosthetic group, these microsomal proteins catalyse the oxygenation of nucleophilic nitrogen, sulphur, phosphorus and selenium atoms in a range of structurally diverse compounds. FMOs have been implicated in the metabolism of a number of pharmaceuticals, pesticides and toxicants. In man, lack of hepatic FMO-catalysed trimethylamine metabolism results in trimethylaminuria (fish odour syndrome). Five mammalian forms of FMO are now known and have been designated FMO1-FMO5 [ 2 , 3 , 4 , 5 , 6 ]. This is a recent nomenclature based on comparison of amino acid sequences, and has been introduced in an attempt to eliminate confusion inherent in multiple, laboratory-specific designations and tissue-based classifications [ 7 ]. Following the determination of the complete nucleotide sequence of Saccharomyces cerevisiae (Baker's yeast) [ 7 ], a novel gene was found to encode a protein with similarity to mammalian monooygenases. In Aspergillus, flavin-containing monooxygenases ustF1 and ustF2 are components in the biosynthesis of the antimitotic tetrapeptide ustiloxin B, a secondary metabolite. The monooxygenases modify the side chain of the intermediate S-deoxyustiloxin H [ 8 ].

1. A nomenclature for the mammalian flavin-containing monooxygenase gene family based on amino acid sequence identities. Arch. Biochem. Biophys. 308, 254-7
2. Cloning, primary sequence, and chromosomal mapping of a human flavin-containing monooxygenase (FMO1). J. Biol. Chem. 266, 12379-85
3. The flavin-containing monooxygenase enzymes expressed in rabbit liver and lung are products of related but distinctly different genes. J. Biol. Chem. 265, 5855-61
4. Molecular cloning of the flavin-containing monooxygenase (form II) cDNA from adult human liver. Proc. Natl. Acad. Sci. U.S.A. 89, 1685-9
5. Cloning, primary sequence and chromosomal localization of human FMO2, a new member of the flavin-containing mono-oxygenase family. Biochem. J. 287 ( Pt 1), 261-7
6. Cloning, sequencing, distribution, and expression in Escherichia coli of flavin-containing monooxygenase 1C1. Evidence for a third gene subfamily in rabbits. J. Biol. Chem. 268, 9681-9
7. Complete nucleotide sequence of Saccharomyces cerevisiae chromosome VIII. Science 265, 2077-82
8. Unveiling the Biosynthetic Pathway of the Ribosomally Synthesized and Post-translationally Modified Peptide Ustiloxin B in Filamentous Fungi. Angew. Chem. Int. Ed. Engl. 55, 8072-5