The yeast Saccharomyces cerevisiae is a powerful experimental system to study biochemical, cell biological and molecular biological aspects of lipid synthesis. Most but not all genes encoding enzymes involved in fatty acid, phospholipid, sterol or sphingolipid biosynthesis of this unicellular eukaryote have been cloned, and many gene products have been functionally characterized. Less information is available about genes and gene products governing the transport of lipids between organelles and within membranes, turnover and degradation of complex lipids, regulation of lipid biosynthesis, and linkage of lipid metabolism to other cellular processes. Here we summarize current knowledge about lipid biosynthetic pathways in S. cerevisiae and describe the characteristic features of the gene products involved. We focus on recent discoveries in these fields and address questions on the regulation of lipid synthesis, subcellular localization of lipid biosynthetic steps, cross-talk between organelles during lipid synthesis and subcellular distribution of lipids. Finally, we discuss distinct functions of certain key lipids and their possible roles in cellular processes.

Biochemistry, Cell Biology and Molecular Biology of Lipids of Saccharomyces cerevisiae

Cholesterol and its relatives possessing the 1,2-cyclopentanoperhydrophenanthrene ring system (Figure ​(Figure1)1) form the sterolome, which comprises a chemical library of more than 1000 natural products found in all forms of eukaryotes and some prokaryotes that serve a myriad of biological functions.1,2 The structural and stereochemical commonality of these compounds derive in large part from the action of oxidosqualene synthases (formerly cyclases) that generate the parent sterol frame. In their 1985 Nobel lecture, Brown and Goldstein stated that “cholesterol is the most highly decorated small molecule in biology”, a comment supported by the many Nobel prizes awarded to individuals who devoted a large part of their lives to research one or more aspects of the chemistry and chemical biology of sterols, their metabolites, or other isoprenoids.2,3



Figure 1

Common tetracyclic steroid frame containing the 1,2-cyclopentanoperhydrophenanthrene ring skeleton.

Biosynthesis of cholesterol and other sterols.

When considering the evolution of desaturases, several different aspects come into focus, the most obvious ones being phylogenetic origins and differentiation of regioselectivities of these enzymes. In this general context the term desaturase includes all enzymes able to activate oxygen and to use this reagent for a subsequent modification of C–H bonds at saturated or monounsaturated carbons in substrates as diverse as alkyl groups, acyl residues in thio-, amideor oxygen-ester linkage, carotenoids, sphingolipids, aldehydes and sterols [1,2]. The presently known oxygen-dependent modifications do not only include the formation of cisand transdouble bonds, they also result in the production of acetylenic bonds, insertion of hydroxy or epoxy groups, and even the postulated decarbonylation of aldehydes or dehydrogenation of ubiquinols [3]. This wide spectrum of reactions is catalysed by proteins which all (as extrapolated from the few examples actually studied in detail) may house a di-iron complex held in place by the side chains of suitable amino acids (histidine, aspartate, glutamate and glutamine), although some similar reactions are catalysed by the heme iron of cytochrome P450 isoforms [4]. It should also be pointed out that the mitochondrial dehydrogenation of ubiquinol by the alternative oxidase [3] does not attack a C–H–, but an O–H bond. If the activity of this enzyme does in fact rely on a di-iron centre, it seems to make use of an overpowered reagent for a reaction which normally involves the completely different di-iron–sulphur cluster of the Rieske protein.

The evolution of desaturases.

Fungi are primitive eukaryotes and have adapted to a variety of niches during evolution. Some fungal species may interact with other life forms (plants, insects, mammals), but are considered as pathogens when they cause mild to severe diseases. Chemical control strategies have emerged with the development of several drugs with antifungal activity against pathogenic fungi. Antifungal agents have demonstrated their efficacy by improving patient health in medicine. However, fungi have counteracted antifungal agents in several cases by developing resistance mechanisms. These mechanisms rely on drug resistance genes including multidrug transporters and drug targets. Their regulation is crucial for the development of antifungal drug resistance and therefore transcriptional factors critical for their regulation are being characterized. Recent genome-wide studies have revealed complex regulatory circuits involving these genetic and transcriptional regulators. Here, we review the current understanding of the transcriptional regulation of drug resistance genes from several fungal pathogens including Candida and Aspergillus species.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1567-1364.2009.00578.x

Antifungal drug resistance mechanisms in fungal pathogens from the perspective of transcriptional gene regulation

One stop mycology

Cloning and characterization of the Saccharomyces cerevisiae C-22 sterol desaturase gene, encoding a second cytochrome P-450 involved in ergosterol biosynthesis

B.A. Skaggs

Papers

Cloning and characterization of the Saccharomyces cerevisiae C-22 sterol desaturase gene, encoding a second cytochrome P-450 involved in ergosterol biosynthesis