antifungal-resistant cytochrome P450 enzyme antifungal resistant fungal C-5 sterol desaturase C-5 sterol desaturase is encoded by ERG3 and is an ER-membrane localized enzyme that catalyzes the introduction of a C-5,6 double bond into episterol, as part of the late ergosterol biosynthesis pathway in fungi. Under normal physiological conditions, Erg3 plays an essential role in channeling sterol intermediates toward ergosterol, the primary sterol of fungal membranes that maintains membrane fluidity, integrity, and the function of membrane-associated proteins. When azoles inhibit Erg11, toxic 14-alpha-methylated sterol intermediates accumulate, and Erg3 acts on these intermediates to produce the species that are directly membrane-toxic to the cell. Loss-of-function mutations in ERG3 therefore confer azole tolerance by compromising this toxic conversion, allowing the cell to persist under drug pressure despite being unable to synthesize ergosterol normally. antibiotic_resistance ARO:3009623