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

Biochem Biophys Res Commun. 1989 May 15;160(3):1257-66. doi: 10.1016/s0006-291x(89)80139-1.

Abstract

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 14 alpha-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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Blotting, Western
  • Candida / genetics
  • Cytochrome P-450 Enzyme System*
  • DNA Restriction Enzymes
  • DNA, Fungal / isolation & purification
  • Drug Resistance, Microbial / genetics
  • Genes, Fungal*
  • Ketoconazole / pharmacology*
  • Leucine / physiology
  • NADPH-Ferrihemoprotein Reductase / genetics*
  • Nucleic Acid Hybridization
  • Oxidoreductases / antagonists & inhibitors
  • Phenotype
  • Plasmids
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / growth & development
  • Sterol 14-Demethylase
  • Transformation, Genetic

Substances

  • DNA, Fungal
  • Cytochrome P-450 Enzyme System
  • Oxidoreductases
  • Sterol 14-Demethylase
  • NADPH-Ferrihemoprotein Reductase
  • DNA Restriction Enzymes
  • Leucine
  • Ketoconazole