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A new class of fatty acid allene oxide formed by the DOX-P450 fusion proteins of human and plant pathogenic fungi, C. immitis and Z. tritici.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. (Oliw)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. (Oliw)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. (Oliw)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. (Oliw)
2016 (English)In: Journal of Lipid Research, ISSN 0022-2275, E-ISSN 1539-7262, Vol. 57, no 8, 1518-1528 p.Article in journal (Refereed) Published
Abstract [en]

Linoleate dioxygenase-cytochrome P450 (DOX-CYP) fusion enzymes are common in pathogenic fungi. The DOX domains form hydroperoxy metabolites of 18:2n-6, which can be transformed by the CYP domains to 1,2- or 1,4-diols, epoxy alcohols, or to allene oxides. We have characterized two novel allene oxide synthases (AOSs), namely, recombinant 8R-DOX-AOS of Coccidioides immitis (causing valley fever) and 8S-DOX-AOS of Zymoseptoria tritici (causing septoria tritici blotch of wheat). The 8R-DOX-AOS oxidized 18:2n-6 sequentially to 8R-hydroperoxy-9Z,12Z-octadecadienoic acid (8R-HPODE) and to an allene oxide, 8R(9)-epoxy-9,12Z-octadecadienoic acid, as judged from the accumulation of the α-ketol, 8S-hydroxy-9-oxo-12Z-octadecenoic acid. The 8S-DOX-AOS of Z. tritici transformed 18:2n-6 sequentially to 8S-HPODE and to an α-ketol, 8R-hydroxy-9-oxo-12Z-octadecenoic acid, likely formed by hydrolysis of 8S(9)-epoxy-9,12Z-octadecadienoic acid. The 8S-DOX-AOS oxidized [8R-(2)H]18:2n-6 to 8S-HPODE with retention of the (2)H-label, suggesting suprafacial hydrogen abstraction and oxygenation in contrast to 8R-DOX-AOS. Both enzymes oxidized 18:1n-9 and 18:3n-3 to α-ketols, but the catalysis of the 8R- and 8S-AOS domains differed. 8R-DOX-AOS transformed 9R-HPODE to epoxy alcohols, but 8S-DOX-AOS converted 9S-HPODE to an α-ketol (9-hydroxy-10-oxo-12Z-octadecenoic acid) and epoxy alcohols in a ratio of ∼1:2. Whereas all fatty acid allene oxides described so far have a conjugated diene impinging on the epoxide, the allene oxides formed by 8-DOX-AOS are unconjugated.

Place, publisher, year, edition, pages
2016. Vol. 57, no 8, 1518-1528 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-300963DOI: 10.1194/jlr.M068981ISI: 000380752300018PubMedID: 27282156OAI: oai:DiVA.org:uu-300963DiVA: diva2:953023
Funder
Swedish Research Council, K2013-67X-06523-31-3Knut and Alice Wallenberg Foundation, KAW 2004.0123
Available from: 2016-08-16 Created: 2016-08-16 Last updated: 2016-09-14Bibliographically approved

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Oliw, Ernst HChen, YangJernerén, Fredrik
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