confers_resistance_to_antibiotic derives_from confers_resistance_to_antibiotic voriconazole Candida parapsilosis Erg3 C-5 sterol desaturase with mutations conferring resistance to voriconazole ARO:3009245 Erg3 is a distinct member of the P450 class of enzymes that encodes C-5 sterol desaturase that functions in the late ergosterol biosynthesis pathway in fungi. It catalyzes the introduction of a C-5,6 double bond into episterol and is localized to the ER membrane. Azole-mediated inhibition of Erg11 causes accumulation of toxic 14-alpha-methylated sterol intermediates and Erg3 acts on these intermediates to produce the species that are toxic to the cell. Loss-of-function mutations in ERG3 therefore confer azole tolerance by preventing the conversion of these intermediates into their toxic form, allowing the cell to survive drug exposure despite compromised ergosterol synthesis. There may be a fitness cost due to simultaneous compromises to membrane composition. antibiotic_resistance azole resistant fungal C-5 sterol desaturase antifungal susceptible ERG3 C-5 sterol desaturase