Lanosterol 14α-demethylase (CYP51) (CYP51)

Fungal lanosterol 14α-demethylase, commonly referred to as CYP51 or Erg11, is a vital cytochrome P450 enzyme essential for the biosynthesis of ergosterol, the primary sterol component of fungal cell membranes [1, 2]. It catalyzes the oxidative removal of the 14α-methyl group from lanosterol through three successive monooxygenation steps, a process required to maintain membrane integrity, fluidity, and the function of membrane-bound proteins [6, 13, 17]. This enzyme serves as the primary molecular target for the azole class of antifungal drugs, including fluconazole, voriconazole, and posaconazole [2, 8]. These inhibitors bind to the heme iron within the enzyme's active site, blocking the conversion of lanosterol and leading to the accumulation of toxic 14α-methylated sterol intermediates [1, 4, 10]. The resulting depletion of ergosterol disrupts the fungal cell membrane, leading to inhibited growth and eventual cell death [5, 13]. While CYP51 is highly conserved across biological kingdoms, structural differences between the fungal and human versions allow for therapeutic selectivity, although cross-reactivity with human P450 enzymes remains a key clinical concern regarding drug-drug interactions and toxicity [7, 15].

Other names

Erg11P45014DMLDMSterol 14α-demethylaseCytochrome P450 51CYP51A1

Inhibits the 14α-demethylation of lanosterol by coordinating with the heme iron in the enzyme's active site, leading to ergosterol depletion and accumulation of toxic 14α-methylated sterols, which disrupts fungal cell membrane integrity [1, 4, 8].