||Disruption of the 'Saccharomyces cerevisiae' Gene for NADPH-Cytochrome P450 Reductase Causes Increased Sensitivity to Ketoconazole.
Sutter, T. R. ;
Loper, J. C. ;
||Cincinnati Univ., OH. Coll. of Medicine.;Environmental Protection Agency, Cincinnati, OH. Risk Reduction Engineering Lab.
Fungal genes ;
NADH dehydrogenase ;
Saccharomyces cerevisiae ;
Microbial sensitivity tests ;
Genetic complementation tests ;
Southern blotting ;
Western blotting ;
||Some EPA libraries have a fiche copy filed under the call number shown.
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.)