Overexpression of genes of the fatty acid biosynthetic pathway leads to accumulation of sterols in Saccharomyces cerevisiae.

Saccharomyces cerevisiae strains with deregulated sterol and fatty acid biosynthesis pathways were analysed for sterol and fatty acid content and mRNA profiles, with the aim of identifying interactions between lipid biosynthesis pathways. carboxylase ACC1 and fatty acid synthases FAS1/FAS2 were overexpressed in wild-type and squalene-overproducing strains. ACC1 overexpression led to decreased fatty acid content in the squalene-overproducing strain (factor of 0.7), while sterols and squalene were increased (factor of 1.5). In the wild-type strain, ACC1 overexpression led to increased levels of both fatty acids and squalene/sterols (factors of 4.0 and 1.7, respectively). This parallel activation of the two pathways seems to be due to transcriptional co-regulation of ACC1 and HMG1. While FAS1 and FAS2 overexpression had no effect in the wild-type strain, FAS2 overexpression induced significant increase of sterols and squalene (factors of 7.2 and 1.3, respectively) and a concomitant decrease of both saturated and unsaturated fatty acids in the squalene-overproducing strain (factor of 0.6). The microarray expression profiles showed that genes upregulated in ACC1-overexpressing strains are FAS1, ERG11, ERG28, ERG5, ERG2 and ERG20, supporting the observed increase of zymosterol and saturated fatty acids. The high ACC1 expression level due to overexpression correlated with increased transcript levels of sphingolipid and sterol biosynthesis genes. The relationship between was shown using the Pathway Studio program.

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