Disruption of the Saccharomyces Cerevlsiae gene for NADPH-cytochrome P450 reductase causes increased sensitivity to ketoconazole


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 14α-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. © 1989 Academic Press, Inc.

Publication Title

Biochemical and Biophysical Research Communications