Sterol 24-C-methyltransferase (Erg6p) (Erg6p)

Erg6p, also known as Sterol 24-C-methyltransferase, is a fungal-specific enzyme essential for the biosynthesis of ergosterol, the primary sterol in fungal cell membranes [1, 3]. It catalyzes the transfer of a methyl group from S-adenosyl-L-methionine (SAM) to the C-24 position of sterol precursors such as zymosterol or lanosterol, a biochemical step that is absent in the human cholesterol biosynthetic pathway [10, 11]. This specificity makes Erg6p an attractive therapeutic target for novel antifungal development, as its inhibition disrupts membrane integrity and reduces fungal virulence [1, 7]. In filamentous fungi like Aspergillus fumigatus, the enzyme is essential for viability, while in Candida species, its inhibition or deletion significantly impairs hyphal formation and biofilm development [7, 10]. Although no FDA-approved drugs currently target Erg6p as their primary mechanism, experimental inhibitors like the allosteric compound H55 and various azasterols have shown efficacy in preclinical models [1, 11]. Notably, mutations in the ERG6 gene are associated with clinical resistance to polyene antifungals like amphotericin B, as the resulting loss of ergosterol removes the drug's primary binding target [2, 15].

Other names

Sterol C-24 methyltransferaseDelta(24)-sterol C-methyltransferaseS-adenosylmethionine:delta24-sterol C-methyltransferaseErgosterol biosynthetic protein 6SAM:SMTSCMT

Inhibition of the sterol 24-C-methyltransferase enzyme activity, which prevents the C-24 methylation of sterol precursors (e.g., zymosterol or lanosterol), thereby disrupting the ergosterol biosynthetic pathway and destabilizing the fungal cell membrane.