Control of Ergosterol Biosynthesis in Yeast*

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Abstract
It was demonstrated that the incorporation of radioactivity from 1-14C-acetate into the nonsaponifiable fraction in S. cerevisiae was depressed by the addition of ergosterol to the growth medium under strictly anaerobic conditions. These results suggested that ergosterol in the culture medium might control its own synthesis. Unexpectedly, with cell-free extracts of this organism, ergosterol had no effect on the incorporation of radioactivity from 1-14C-acetate into the nonsaponifiable fraction. However, the acidic lipids extracted from this organism were found to inhibit 14C-incorporation into the nonsaponifiable fraction from 1-14C-acetate as well as from 3-14C-3-hydroxy-3-methyl-glutaryl-CoA, but not from 2-14C-mevalonate. The results suggested that acidic lipids inhibited the reduction of 3-hydroxy-3-methylglutatyl-CoA to mevalonate. The inhibitors were purified by column chromatography followed by thin-layer chromatography. Four compounds which had inhibitory activities were found on the thin-layer plate. One of the inhibitors was purified 1, 000 fold on the basis of its inhibitory activity. The possible role of these inhibitors in the control of ergosterol synthesis in yeast is discussed.

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