title: Stereoselective oxidation of regioisomeric octadecenoic acids by fatty acid dioxygenases.
abstract: Seven Z-octadecenoic acids having the double bond located in positions 6Z to 13Z were photooxidized. The resulting hydroperoxy-E-octadecenoic acids [HpOME(E)] were resolved by chiral phase-HPLC-MS, and the absolute configurations of the enantiomers were determined by gas chromatographic analysis of diastereoisomeric derivatives. The MS/MS/MS spectra showed characteristic fragments, which were influenced by the distance between the hydroperoxide and carboxyl groups. These fatty acids were then investigated as substrates of cyclooxygenase-1 (COX-1), manganese lipoxygenase (MnLOX), and the (8R)-dioxygenase (8R-DOX) activities of two linoleate diol synthases (LDS) and 10R-DOX. COX-1 and MnLOX abstracted hydrogen at C-11 of (12Z)-18:1 and C-12 of (13Z)-18:1. (11Z)-18:1 was subject to hydrogen abstraction at C-10 by MnLOX and at both allylic positions by COX-1. Both allylic hydrogens of (8Z)-18:1 were also abstracted by 8R-DOX activities of LDS and 10R-DOX, but only the allylic hydrogens close to the carboxyl groups of (11Z)-18:1 and (12Z)-18:1. 8R-DOX also oxidized monoenoic C(14)-C(20) fatty acids with double bonds at the (9Z) position, suggesting that the length of the omega end has little influence on positioning for oxygenation. We conclude that COX-1 and MnLOX can readily abstract allylic hydrogens of octadecenoic fatty acids from C-10 to C-12 and 8R-DOX from C-7 and C-12.
authors.affiliation: Department of Pharmaceutical Biosciences, Division of Biochemical Pharmacology, Uppsala Biomedical Center, SE-75124, Uppsala, Sweden. Ernst.Oliw@farmbio.uu.se
authors.forename: Ernst H
authors.initials: EH
authors.lastname: Oliw
authors.forename: Anneli
authors.initials: A
authors.lastname: Wennman
authors.forename: Inga
authors.initials: I
authors.lastname: Hoffmann
authors.forename: Ulrike
authors.initials: U
authors.lastname: Garscha
authors.forename: Mats
authors.initials: M
authors.lastname: Hamberg
authors.forename: Fredrik
authors.initials: F
authors.lastname: Jernerén
mesh_terms: D000818:Animals; D001203:Ascomycota / Q000201:enzymology; D001232:Aspergillus fumigatus / Q000201:enzymology; D055162:Biocatalysis; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D049308:Dioxygenases / Q000235:genetics / Q000378:metabolism*; D006418:Heme / Q000378:metabolism; D013058:Mass Spectrometry; D010084:Oxidation-Reduction; D055668:Photochemical Processes; D017354:Point Mutation; D017384:Sequence Deletion; D012756:Sheep; D013229:Stearic Acids / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D013237:Stereoisomerism; D013379:Substrate Specificity
chemical_list: C114874:5-octadecenoic acid; D013229:Stearic Acids; D006418:Heme; D049308:Dioxygenases