title: 8R-Lipoxygenase-catalyzed synthesis of a prominent cis-epoxyalcohol from dihomo-γ-linolenic acid: a distinctive transformation compared with S-lipoxygenases.
abstract: Conversion of fatty acid hydroperoxides to epoxyalcohols is a well known secondary reaction of lipoxygenases, described for S-specific lipoxygenases forming epoxyalcohols with a trans-epoxide configuration. Here we report on R-specific lipoxygenase synthesis of a cis-epoxyalcohol. Although arachidonic and dihomo-γ-linolenic acids are metabolized by extracts of the Caribbean coral Plexaura homomalla via 8R-lipoxygenase and allene oxide synthase activities, 20:3ω6 forms an additional prominent product, identified using UV, GC-MS, and NMR in comparison to synthetic standards as 8R,9S-cis-epoxy-10S-erythro-hydroxy-eicosa-11Z,14Z-dienoic acid. Both oxygens of (18)O-labeled 8R-hydroperoxide are retained in the product, indicating a hydroperoxide isomerase activity. Recombinant allene oxide synthase formed only allene epoxide from 8R-hydroperoxy-20:3ω6, whereas two different 8R-lipoxygenases selectively produced the epoxyalcohol.A biosynthetic scheme is proposed in which a partial rotation of the reacting intermediate is required to give the observed erythro epoxyalcohol product. This characteristic and the synthesis of cis-epoxy epoxyalcohol may be a feature of R-specific lipoxygenases.
authors.affiliation: Department of Pharmacology, and the Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, TN, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Jin
authors.forename: William E
authors.initials: WE
authors.lastname: Boeglin
authors.forename: Jin K
authors.initials: JK
authors.lastname: Cha
authors.forename: Alan R
authors.initials: AR
authors.lastname: Brash
mesh_terms: D015126:8,11,14-Eicosatrienoic Acid / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D037421:Anthozoa / Q000201:enzymology; D001091:Arachidonate Lipoxygenases / Q000378:metabolism*; D004852:Epoxy Compounds / Q000737:chemistry / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D008084:Lipoxygenase / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D013379:Substrate Specificity
chemical_list: D004852:Epoxy Compounds; D001091:Arachidonate Lipoxygenases; D008084:Lipoxygenase; C054192:arachidonate 8-lipoxygenase; D019746:Intramolecular Oxidoreductases; C021377:hydroperoxide isomerase; D015126:8,11,14-Eicosatrienoic Acid