Selective Inhibition of the Demethylation at C-14 in Ergosterol Biosynthesis by the Fungicide, Denmert (S-1358)

Abstract

In cell-free homogenates of Saccharomyces cerevisiae, Denmert (S-1358) inhibited the incorporation of radioactivity from dl-mevalonate-2-¹⁴C into 14-desmethyl-lanosterol, 4α-methyl-cholesta-8,24-dien-3-one, 4α-methyl-zymosterol and 4-desmethyl sterols (zymosterol and episterol) at a concentration of 10⁻⁴ m. Concomitantly, a large accumulation of radioactivity was observed in the Ianosterol fraction. In good agreement with the results described above, Denmert inhibited the conversion of ¹⁴C-labeled lanosterol to 4-desmethyl sterols, while the conversion of ¹⁴C-labeled 14-desmethyl-lanosterol to 4-desmethyl sterols was hardly affected by the fungicide. It is therefore evident that Denmert is a potent selective inhibitor of the demethylation at the C–14 position in ergosterol biosynthesis. The fungicide, triarimol, was also found to exhibit the same effect on sterol biosynthesis as Denmert.