Sterol C-5 desaturase (ERG3) (ERG3)

Sterol C-5 desaturase, primarily known as ERG3 in fungal species, is a critical enzyme within the ergosterol biosynthesis pathway responsible for introducing a double bond at the C-5 position of the sterol nucleus (UniProt: P32353). Ergosterol is an essential component of fungal cell membranes, performing functions similar to cholesterol in humans by regulating membrane fluidity, permeability, and the function of membrane-bound proteins (NCBI Gene: 855700). This enzyme is a significant target in antifungal research because its inhibition or dysfunction disrupts the production of ergosterol, leading to compromised cell membrane integrity and inhibited fungal growth. Interestingly, ERG3 is also a major player in antifungal resistance; mutations that inactivate ERG3 allow fungi to bypass the lethal accumulation of toxic sterols typically caused by azole drugs, which target the upstream enzyme ERG11 (PMID: 21633012). In humans, the orthologous enzyme is Sterol-C5-desaturase (SC5D), and its deficiency is linked to the rare metabolic disorder lathosterolosis, highlighting the need for high selectivity in antifungal drug design (UniProt: Q15884; PMID: 10430571). Consequently, Sterol C-5 desaturase represents both a vulnerability in fungal pathogens and a complex factor in the evolution of clinical drug resistance.

Other names

C-5 sterol desaturaseErgosterol biosynthesis protein 3ERG3pSterol C-5(6) desaturaseSC5D

Inhibition of the C-5(6) desaturation of episterol to ergosta-5,7,24(28)-trien-3β-ol, leading to ergosterol depletion and accumulation of atypical sterols that disrupt membrane integrity.