Sterol Delta(8)-Delta(7)-isomerase (ERG2) (ERG2)

Sterol Delta(8)-Delta(7)-isomerase (ERG2) is a vital enzyme in the fungal ergosterol biosynthetic pathway, responsible for the conversion of fecosterol to episterol by shifting the double bond from the C8 to the C7 position (UniProt P32352). Ergosterol is the fungal equivalent of cholesterol and is essential for maintaining the structural integrity, fluidity, and function of the fungal cell membrane (PubMed: 10.1128/AAC.44.5.1154-1160.2000). This enzyme is a primary target for the morpholine class of antifungal drugs, such as amorolfine and fenpropimorph, which are used to treat various fungal infections including onychomycosis and cutaneous candidiasis (DrugBank DB09055). Inhibition of the isomerase leads to a depletion of ergosterol and an accumulation of abnormal sterols like ignosterol, which disrupts membrane permeability and inhibits fungal growth (PubMed: 10.1016/S0168-6445(03)00049-X). While the enzyme has a human ortholog known as the emopamil binding protein (EBP), the specificity of certain inhibitors for the fungal form allows for therapeutic use, primarily in topical applications to minimize systemic toxicity (PubMed: 10.1074/jbc.271.38.23250). The enzyme is localized to the endoplasmic reticulum and is highly conserved across various fungal species, including Saccharomyces cerevisiae and Candida albicans. Resistance to drugs targeting this enzyme can occur through mutations in the ERG2 gene or upregulation of alternative sterol pathways.

Other names

Delta(8)-Delta(7)-isomeraseErg2pCholestenol Delta-isomeraseFungal Delta 7,8-isomerase

Inhibition of the sterol Delta(8)-Delta(7)-isomerase enzyme, which prevents the conversion of fecosterol to episterol, leading to the depletion of ergosterol and the accumulation of toxic sterol intermediates like ignosterol, thereby disrupting fungal cell membrane integrity and function.