Expression, purification, reconstitution and inhibition of Ustilago maydis sterol 14 alpha-demethylase (CYP51; P450(14DM))

FEMS Microbiol Lett. 1998 Dec 15;169(2):369-73. doi: 10.1111/j.1574-6968.1998.tb13342.x.

Abstract

Triadimenol and tebuconazole are potent inhibitors of the sterol 14 alpha-demethylation reaction in fungi which is catalysed by CYP51, a haem-thiolate containing enzyme belonging to the cytochrome P450 monooxygenase superfamily. Using CYP51 from the phytopathogen Ustilago maydis, a comparison of the sensitivity of the fungal enzyme to triadimenol and tebuconazole has been carried out. U. maydis CYP51 was purified to homogeneity as determined by SDS-PAGE and specific haem content. Catalytic activity was investigated following reconstitution with its respective NADPH cytochrome P450 reductase and proposed endogenous substrate, 24-methylenedihydrolanosterol. Addition of the triadimenol and tebuconazole induced type II spectral changes in the enzyme, with saturation occurring at equimolar azole concentrations. Inhibition of reconstituted activities showed a one-to-one sensitivity of the fungal CYP51 as judged by IC50 values. The implications for fungicide mode of action and treatment are discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Azoles / pharmacology
  • Cloning, Molecular
  • Cytochrome P-450 Enzyme Inhibitors
  • Cytochrome P-450 Enzyme System* / isolation & purification
  • Cytochrome P-450 Enzyme System* / physiology
  • Electrophoresis, Polyacrylamide Gel
  • Molecular Sequence Data
  • Oxidoreductases* / antagonists & inhibitors
  • Oxidoreductases* / isolation & purification
  • Oxidoreductases* / physiology
  • Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Spectrophotometry
  • Sterol 14-Demethylase
  • Triazoles / pharmacology
  • Ustilago / enzymology*

Substances

  • Azoles
  • Cytochrome P-450 Enzyme Inhibitors
  • Triazoles
  • triadimefon
  • tebuconazole
  • Cytochrome P-450 Enzyme System
  • Oxidoreductases
  • Sterol 14-Demethylase