title: A linoleic acid (8R)-dioxygenase and hydroperoxide isomerase of the fungus Gaeumannomyces graminis. Biosynthesis of (8R)-hydroxylinoleic acid and (7S,8S)-dihydroxylinoleic acid from (8R)-hydroperoxylinoleic acid.
abstract: The fungus Gaeumannomyces graminis metabolized linoleic acid extensively to (8R)-hydroperoxylinoleic acid, (8R)-hydroxylinoleic acid, and threo-(7S,8S)-dihydroxylinoleic acid. When G. graminis was incubated with linoleic acid under an atmosphere of oxygen-18, the isotope was incorporated into (8R)-hydroxylinoleic acid and 7,8-dihydroxylinoleic acid. The two hydroxyls of the latter contained either two oxygen-18 or two oxygen-16 atoms, whereas a molecular species that contained both oxygen isotopes was formed in negligible amounts. Glutathione peroxidase inhibited the biosynthesis of 7,8-dihydroxylinoleic acid. These findings demonstrated that the diol was formed from (8R)-hydroperoxylinoleic acid by intramolecular hydroxylation at carbon 7, catalyzed by a hydroperoxide isomerase. The (8R)-dioxygenase appeared to metabolize substrates with a saturated carboxylic side chain and a 9Z-double bond. G. graminis also formed omega 2- and omega 3-hydroxy metabolites of the fatty acids. In addition, linoleic acid was converted to small amounts of nearly (65% R) racemic 10-hydroxy-8,12-octadecadienoic acid by incorporation of atmospheric oxygen. An unstable metabolite, 11-hydroxylinoleic acid, could also be isolated as well as (13R,13S)-hydroxy-(9E,9Z), (11E)-octadecadienoic acids and (9R,9S)-hydroxy-(10E), (12E,12Z)-octadecadienoic acids. In summary, G. graminis contains a prominent linoleic acid (8R)-dioxygenase, which differs from the lipoxygenase family of dioxygenases by catalyzing the formation of a hydroperoxide without affecting the double bonds of the substrate.
authors.affiliation: Department of Pharmaceutical Pharmacology, Uppsala University Biomedical Center, Sweden.
authors.forename: I D
authors.initials: ID
authors.lastname: Brodowsky
authors.forename: M
authors.initials: M
authors.lastname: Hamberg
authors.forename: E H
authors.initials: EH
authors.lastname: Oliw
mesh_terms: D001203:Ascomycota / Q000201:enzymology*; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D008401:Gas Chromatography-Mass Spectrometry; D019746:Intramolecular Oxidoreductases; D007535:Isomerases / Q000378:metabolism*; D008041:Linoleic Acids / Q000096:biosynthesis* / Q000378:metabolism*
chemical_list: D008041:Linoleic Acids; C075806:8-hydroxylinoleic acid; C075808:7,8-dihydroxylinoleic acid; C075807:8-hydroperoxylinoleic acid; D007535:Isomerases; D019746:Intramolecular Oxidoreductases; C021377:hydroperoxide isomerase