Lanosterol 14-alpha demethylase (ERG11) (ERG11)

Lanosterol 14-alpha demethylase, commonly referred to as ERG11 in fungi like Candida albicans, is a critical enzyme in the ergosterol biosynthetic pathway (UniProt, 2024). It belongs to the cytochrome P450 superfamily and catalyzes the oxidative removal of the 14-alpha-methyl group from lanosterol or eburicol (PubMed, PMID: 10896671). Because ergosterol is a vital component of fungal cell membranes—analogous to cholesterol in humans—this enzyme is essential for maintaining membrane integrity, fluidity, and the function of membrane-bound proteins (StatPearls, 2023). In the context of human health, it serves as the primary target for the azole class of antifungal medications used to treat a wide range of systemic and mucosal fungal infections, such as candidiasis and aspergillosis (NIH, 2023). Azole drugs bind to the heme iron within the enzyme's active site, effectively blocking its catalytic activity (PubChem, 2024). This inhibition leads to a lethal depletion of ergosterol and the accumulation of toxic methylated sterol intermediates, which ultimately results in fungal growth inhibition or cell death (Journal of Fungi, 2021). However, the clinical utility of targeting ERG11 is often challenged by the development of drug resistance through genetic mutations and the potential for off-target inhibition of human cytochrome P450 enzymes (Nature Communications, 2022).

Other names

CYP51Lanosterol 14-alpha-demethylaseErgosterol biosynthesis protein 11P45014DMCytochrome P450 5114-alpha-demethylase

Inhibition of the enzyme by binding to the heme iron within the active site, preventing the demethylation of lanosterol, which leads to ergosterol depletion and the accumulation of toxic 14-alpha-methyl sterols (StatPearls, 2023).