Candida albicans Spt23p controls the expression of the Ole1p Δ9 fatty acid desaturase and regulates unsaturated fatty acid biosynthesis

Abstract

In Saccharomyces cerevisiae the endoplasmic reticulum membrane proteins scSpt23p and scMga2p control the formation of unsaturated fatty acids by a mechanism that involves their release from the membrane by ubiquitin-mediated proteolysis. The resulting soluble polypeptides act as transcription activators that specifically control the expression of scOLE1, a gene that encodes scOle1p, a Δ9 fatty acid desaturase that forms cis-monounsaturated fatty acids (9Z-16:1 and 9Z-18:1) from saturated fatty acyl-CoA precursors. ScOle1p is the only long chain fatty acid desaturase in Saccharomyces and its membrane and storage lipids contain only saturated fatty acids and the monounsaturated products of that enzyme. Most other fungi, however, express multiple endoplasmic reticulum desaturases, including enzymes that form both mono- and polyunsaturated fatty acids. These typically include Δ12 and Δ15 enzymes that form the polyunsaturated species, 9Z,12Z-18:2, and 9Z,12Z,15Z-18:3, which are the most abundant fatty acids in membrane and storage lipids. An analysis of genomic DNA sequences shows that Candida albicans has a single homologue of the Saccharomyces scSPT23 and scMGA2 genes that we designate here as caSPT23. This study describes the characterization of the caSPT23 gene product and shows that it can repair the unsaturated fatty acid auxotrophy when it is expressed in a Saccharomyces scspt23Δ;scmga2 Δ strain. In addition we show caSPT23 is essential for the expression of one of the two Δ9 desaturase homologues in Candida and potentially other functions associated with fatty acid metabolism. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.