title: Drosophila melanogaster CYP6A8, an insect P450 that catalyzes lauric acid (omega-1)-hydroxylation.
abstract: Only a handful of P450 genes have been functionally characterized from the approximately 90 recently identified in the genome of Drosophila melanogaster. Cyp6a8 encodes a 506-amino acid protein with 53.6% amino acid identity with CYP6A2. CYP6A2 has been shown to catalyze the metabolism of several insecticides including aldrin and heptachlor. CYP6A8 is expressed at many developmental stages as well as in adult life. CYP6A8 was produced in Saccharomyces cerevisiae and enzymatically characterized after catalytic activity was reconstituted with D. melanogaster P450 reductase and NADPH. Although several saturated or non-saturated fatty acids were not metabolized by CYP6A8, lauric acid (C12:0), a short-chain unsaturated fatty acid, was oxidized by CYP6A8 to produce 11-hydroxylauric acid with an apparent V(max) of 25 nmol/min/nmol P450. This is the first report showing that a member of the CYP6 family catalyzes the hydroxylation of lauric acid. Our data open new prospects for the CYP6 P450 enzymes, which could be involved in important physiological functions through fatty acid metabolism.
authors.affiliation: Department of Chemistry, The University of Arizona, Tucson, AZ 85721, USA. christian@cytochroma.com
authors.forename: Christian
authors.initials: C
authors.lastname: Helvig
authors.forename: Nathalie
authors.initials: N
authors.lastname: Tijet
authors.forename: René
authors.initials: R
authors.lastname: Feyereisen
authors.forename: F Ann
authors.initials: FA
authors.lastname: Walker
authors.forename: Linda L
authors.initials: LL
authors.lastname: Restifo
mesh_terms: D000452:Aldrin / Q000737:chemistry*; D000818:Animals; D002384:Catalysis; D042926:Cytochrome P-450 CYP4A / Q000737:chemistry / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry* / Q000378:metabolism*; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000201:enzymology*; D007850:Lauric Acids / Q000737:chemistry* / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D007850:Lauric Acids; C030358:lauric acid; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C495067:CYP6A8 protein, Drosophila; D042926:Cytochrome P-450 CYP4A; D000452:Aldrin