Mutations in erg4 affect the sensitivity of Saccharomyces cerevisiae to medium-chain fatty acids

We have found that the medium-chain fatty acids (MCFAs) undecanoic acid (11:0), 10-undecenoic acid (11:1Delta10), and lautic acid (12:0) can affect the growth of Saccharomyces cerevisiae in a dose-dependent manner. The principal effect was a longer lag phase in MCFA-containing medium, although higher concentrations of 11:1Delta10 inhibited growth. Their relative order of inhibitory action was 11:1Delta10>11:0>12:0. Cellular content with MCFA supplementation A as dependent on the concentration and the particular species of fatty acid, with 12:0 showing the highest relative accumulation and 11:1Delta10 the lowest at all concentrations, We have isolated and characterized a mutant that is hypersensitive to MCFA supplementation and is unable to grow at the normally permissive condition of 1 mM 11:1Delta10. However, it does not appear to accumulate higher relative levels of the fed MCFA compared to wild-type cells. Complementation of the mutant revealed that the ERG4 gene, encoding the enzyme that catalyzes the last step in ergosterol biosynthesis, had been mutated. The fatty acid composition of the erg4Delta mutant differs only slightly from wild-type cells, mainly involving an increase in the relative amount of 12:0. These results indicate that yeast require ergosterol for optimal growth on certain MCFAs. We discuss the role ergosterol may have in cells responding to exogenous MCFAs and in supporting optimal cell growth. (C) 2002 Elsevier Science B.V. All rights reserved.