Cytochrome P450 Lanosterol 14α-demethylase (CYP51): Insights from Molecular Genetic Analysis of the ERG11 Gene in Saccharomyces Cerevisiae

Eukaryotes characteristically express a cytochrome P450-catalyzed sterol 14α-methyl demethylase as an essential step in the production of membrane sterols. Lanosterol 14α-demethylase of Saccharomyces cerevisiae is the best characterized representative of these enzymes among fungi and provides a model system for the molecular genetic analysis of the reaction. The gene for this P450 and the gene for the S. cerevisiae NADPH-cytochrome P450 reductase have been examined by mutational inactivation and for their regulation of expression. Our results have contributed to a better understanding of sterol biosynthesis in relation to mechanisms of resistance to fungicidal demethylase inhibitors, and promote the rationale for using S. cerevisiae in the further characterization of structure function relationships among sterol 14α-demethylases.