Cytochrome P450 lanosterol 14α-demethylase (CYP51)

Cytochrome P450 lanosterol 14α-demethylase (CYP51) is a highly conserved enzyme found in eukaryotes and is essential for the biosynthesis of sterols—specifically, it catalyzes the oxidative removal of the 14α-methyl group from lanosterol in animals and fungi, and other related sterol precursors in plants[1][3][6]. This three-step monooxygenase reaction requires molecular oxygen and NADPH and is crucial for producing ergosterol in fungi and cholesterol in mammals[1][4][6][7]. CYP51 enzymes are the sole P450 family members with a conserved catalytic function across kingdoms. In fungi, CYP51 (encoded by ERG11) is the molecular target of azole antifungal agents; its inhibition disrupts membrane integrity, inhibiting fungal growth and viability[2][3][6]. Resistance can arise through gene mutation or overexpression. In mammals, the enzyme is also involved in reproductive development and cell signalling, with distinct cellular localization patterns in specific tissues (e.g., acrosomal membranes in germ cells)[4]. Proximal inhibition in mammals risks interfering with cholesterol biosynthesis, making selectivity important for drug design.

Other names

Lanosterol 14α-demethylaseSterol 14α-demethylaseP45014DMErg11 (in fungi)CYP51A1 (human gene)

Inhibition of enzyme activity by azole drugs, blocking ergosterol or cholesterol biosynthesis by binding to the heme iron and preventing demethylation of lanosterol, leading to accumulation of toxic sterol intermediates and membrane disruption