Isolation and analysis of ketoconazole resistant mutants of Saccharomyces cerevisiae.
Nine mutants of Saccharomyces cerevisiae which are resistant to ketoconazole, have been isolated and characterized. In each case the mutation is nuclear in origin and allelic to a previously described mutation, erg3, which gives rise to a block in the delta 5-6 desaturation step of ergosterol biosynthesis. The significance of this second site mutation to the point of inhibitory action of ketoconazole, that is the P-450-mediated C-14 demethylation of lanosterol, is discussed.
D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004352:Drug Resistance, Microbial / Q000235:genetics; D004875:Ergosterol / Q000096:biosynthesis; D008401:Gas Chromatography-Mass Spectrometry; D005816:Genetic Complementation Test; D007654:Ketoconazole / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D013056:Spectrophotometry, Ultraviolet
D003577:Cytochrome P-450 Enzyme System; D007654:Ketoconazole; D004875:Ergosterol