Disruption of the 'Saccharomyces cerevisiae' Gene for NADPH-Cytochrome P450 Reductase Causes Increased Sensitivity to Ketoconazole

摘要

Strains of Saccharomyces cerevisiae deleted in the NADPH-cytochrome P450 reductase gene by transplacement are 200-fold more sensitive to ketoconazole, an inhibitor of the cytochrome P450 lanosterol 14alpha-demethylase. Resistance is restored through complementation by the plasmid-borne wild type gene from either S. cerevisiae or Candida tropicalis. Neither Southern hybridization nor Western immunoblot techniques provided evidence for a second NADPH-cytochrome P450 reductase gene, suggesting that an alternate pathway may provide for the functions of this reductase in S. cerevisiae. (Copyright (c) 1989 Academic Press, Inc.)