Sterol delta-8,delta-7-isomerase (ERG2)

Sterol delta-8,delta-7-isomerase, also known as ERG2, is a membrane-bound enzyme essential for the biosynthesis of ergosterol in fungi [1, 3]. It catalyzes the isomerization of fecosterol to episterol by transposing the double bond from the C8 to the C7 position in the sterol B-ring [4, 12]. Ergosterol is the primary sterol in fungal cell membranes, maintaining fluidity and integrity, much like cholesterol in mammalian cells [5, 8]. This enzyme is a major target for morpholine antifungals such as amorolfine and fenpropimorph [1, 2]. Inhibition of the enzyme leads to ergosterol depletion and the accumulation of abnormal sterols, which disrupts membrane function and inhibits fungal growth [3, 4]. Although it has a human homolog called emopamil-binding protein (EBP), the fungal enzyme is a validated target for topical antifungal therapy [4, 6]. Mutations in the human homolog are associated with X-linked chondrodysplasia punctata, highlighting the importance of selectivity in drug design [10, 12].

Other names

Fungal Cholestenol Δ8-Δ7 isomeraseCholestenol delta-isomeraseC8-C7 sterol isomerase3-beta-hydroxysteroid-Delta(8),Delta(7)-isomeraseErg2pDelta8-Delta7 sterol isomerase

Inhibition of the sterol delta-8,delta-7-isomerase enzyme, which prevents the conversion of fecosterol to episterol, leading to ergosterol depletion and accumulation of atypical sterol intermediates [1, 3, 4].