CYP51

CYP51, or cytochrome P450 family 51, is a gene encoding lanosterol 14-demethylase, a heme-containing monooxygenase that catalyzes the removal of a methyl group at carbon 14 from sterol precursors in the sterol biosynthesis pathway. This demethylation is a key step in the production of sterols, including ergosterol in fungi and cholesterol in animals and plants. The enzyme is typically located in the endoplasmic reticulum and functions with NADPH-cytochrome P450 reductase to introduce oxygen into the substrate.

Molecularly, CYP51 is a member of the cytochrome P450 superfamily and contains a heme-iron thiolate active site. Conserved motifs such as the cysteine-containing heme-binding signature FGxGxCxG, along with PERF and EXXR regions, support catalysis and substrate interaction. The enzyme’s activity is essential for maintaining proper membrane composition, as sterol content influences membrane fluidity and permeability.

Taxonomic distribution and nomenclature vary: CYP51 is present across eukaryotes. In fungi, the gene is commonly known as ERG11 and is essential for ergosterol synthesis; in animals and plants, CYP51A1 and homologs participate in cholesterol biosynthesis. Inhibitors of CYP51, particularly azole antifungals (for example, fluconazole, itraconazole) and agricultural azoles, bind the heme iron and block demethylation, causing defective membranes and inhibited growth. Resistance can arise through point mutations, gene amplification, or increased efflux.

Genetic and pharmaceutical relevance: CYP51 is a validated drug target for antifungal therapy and crop protection. Structural and kinetic studies of CYP51 inform substrate specificity and resistance mechanisms and aid in designing new inhibitors.