Requirement of sphingolipid alpha-hydroxylation for fungicidal action of syringomycin E

Syringomycin E is an antifungal cyclic lipodepsinonapeptide produced by Pse udomonas syringae pv. syringae. To understand the mechanism of action of sy ringomycin E, a novel resistant Saccharomyces cerevisiae strain, BW7, was i solated and characterized. Lipid analyses revealed that BW7 contained only the hydrophobic subspecies of sphingolipids that are normally minor compone nts in wild type strains. This aberrant sphingolipid composition was the re sult of lack of alpha-hydroxylation of the amide-linked very long chain fat ty acids, suggesting a defective sphingolipid alpha-hydroxylase encoded by the FAH1 gene. A yeast strain that lacks the FAH1 gene was resistant to syr ingomycin E, and failed to complement BW7. These results demonstrate that B W7 carries a mutation in the FAH1 gene, and that the Lack of alpha-hydroxyl ated very long chain fatty acids in yeast sphingolipids confers resistance to syringomycin E, (C) 2000 Federation of European Biochemical Societies. P ublished by Elsevier Science B.V. All rights reserved.