title: The Saccharomyces cerevisiae YBR159w gene encodes the 3-ketoreductase of the microsomal fatty acid elongase.
abstract: The YBR159w gene encodes the major 3-ketoreductase activity of the elongase system of enzymes required for very long-chain fatty acid (VLCFA) synthesis. Mutants lacking the YBR159w gene display many of the phenotypes that have previously been described for mutants with defects in fatty acid elongation. These phenotypes include reduced VLCFA synthesis, accumulation of high levels of dihydrosphingosine and phytosphingosine, and accumulation of medium-chain ceramides. In vitro elongation assays confirm that the ybr159Delta mutant is deficient in the reduction of the 3-ketoacyl intermediates of fatty acid elongation. The ybr159Delta mutant also displays reduced dehydration of the 3-OH acyl intermediates of fatty acid elongation, suggesting that Ybr159p is required for the stability or function of the dehydratase activity of the elongase system. Green fluorescent protein-tagged Ybr159p co-localizes and co-immunoprecipitates with other elongating enzymes, Elo3p and Tsc13p. Whereas VLCFA synthesis is essential for viability, the ybr159Delta mutant cells are viable (albeit very slowly growing) and do synthesize some VLCFA. This suggested that a functional ortholog of Ybr159p exists that is responsible for the residual 3-ketoreductase activity. By disrupting the orthologs of Ybr159w in the ybr159Delta mutant we found that the ybr159Deltaayr1Delta double mutant was inviable, suggesting that Ayr1p is responsible for the residual 3-ketoreductase activity.
authors.affiliation: Department of Biochemistry and Molecular Biology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20184, USA.
authors.forename: Gongshe
authors.initials: G
authors.lastname: Han
authors.forename: Ken
authors.initials: K
authors.lastname: Gable
authors.forename: Sepp D
authors.initials: SD
authors.lastname: Kohlwein
authors.forename: Frédéric
authors.initials: F
authors.lastname: Beaudoin
authors.forename: Johnathan A
authors.initials: JA
authors.lastname: Napier
authors.forename: Teresa M
authors.initials: TM
authors.lastname: Dunn
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000235:genetics* / Q000378:metabolism; D000123:Acetyltransferases / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism; D002518:Ceramides / Q000378:metabolism; D015825:Chromosomes, Fungal; D017931:DNA Primers; D000081031:Fatty Acid Elongases; D005800:Genes, Fungal; D005804:Genes, Lethal; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins / Q000235:genetics; D008856:Microscopy, Fluorescence; D008861:Microsomes / Q000201:enzymology*; D010641:Phenotype; D011993:Recombinant Fusion Proteins / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D002518:Ceramides; D017931:DNA Primers; D008164:Luminescent Proteins; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D049452:Green Fluorescent Proteins; D015094:3-Hydroxyacyl CoA Dehydrogenases; C579561:YBR159W protein, S cerevisiae; D000123:Acetyltransferases; D000081031:Fatty Acid Elongases; D002118:Calcium