The induced biosynthesis of 7-dehydrocholesterols in yeast: potential sources of new provitamin D3 analogs

Abstract

The effect of low concentrations of a specifically designed sterol-24-transmethylase inhibitor, 25-aza-24,25-dihydrozymosterol (10) on sterol production in Saccharomyces cerevisiae was examined. The synthesis of cholesta-5,7,22,24-tetraen-3β-ol (4), its 7,22,24 analog (15) and the 7,24 analog (5) coupled with the availability of zymosterol (6) and cholesta-5,7,24-3β-ol (3) derivatives facilitated a search for these sterols in cultures treated with this inhibitor.When S. cerevisiae was grown in the presence of 1.3 and 5 μM10, it produced no ergosterol but accumulated zymosterol (6), cholesta-5,7,22, 24-tetraen-3β-ol (4) and related C27 sterols (3 and 5). These results indicate blockage of the side chain methylation that normally occurs during the biosynthesis of ergosterol in yeast by compound 10 is efficient. The cholesta-5,7,22,24-tetraen-3β-ol is a close structural analog of provitamin D3 (7-dehydrocholesterol). The inhibited yeast thus provides a source of a potentially new provitamin D3 substitute.