The Saccharomyces cerevisiae YBR159w gene encodes the 3-ketoreductase of the microsomal fatty acid elongase

被引:87
作者
Han, GS
Gable, K
Kohlwein, SD
Beaudoin, F
Napier, JA
Dunn, TM
机构
[1] Uniformed Serv Univ Hlth Sci, Dept Biochem & Mol Biol, Bethesda, MD 20184 USA
[2] Inst Arable Crops Res, Long Ashton Res Stn, Bristol BS41 9AF, Avon, England
[3] Graz Univ, SFB Biomembrane Res Ctr, Dept Mol Biol Biochem & Microbiol, A-8010 Graz, Austria
基金
英国生物技术与生命科学研究理事会;
关键词
D O I
10.1074/jbc.M205620200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 Ybrl59p co-localizes and co-immunoprecipitates with other elongating enzymes, Elo3p and Tsc13p. Whereas V-LCFA 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.
引用
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页码:35440 / 35449
页数:10
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