Squalene monooxygenase (ERG1) (ERG1)

Squalene monooxygenase (ERG1) is a vital enzyme in the ergosterol biosynthesis pathway of Candida species, catalyzing the conversion of squalene to 2,3-oxidosqualene (UniProt: P36595). This step is rate-limiting and essential for maintaining the structural integrity and fluidity of the fungal cell membrane (PubMed: 25118202). In Candida infections, this enzyme is the primary target for allylamine antifungals such as terbinafine, which bind non-competitively to inhibit its activity (PubChem: CID 154909). The resulting depletion of ergosterol and the toxic accumulation of squalene droplets lead to fungal cell death (PubMed: 17075250). While highly selective for the fungal enzyme over the human homolog, resistance can develop through specific point mutations in the ERG1 gene, particularly in non-albicans Candida species (PubMed: 31636076). Understanding the structural biology of this enzyme is crucial for developing next-generation antifungals that can overcome emerging resistance patterns.

Other names

Squalene epoxidaseSESqualene 2,3-epoxidaseERG1p

Non-competitive inhibition of squalene monooxygenase, which prevents the conversion of squalene to 2,3-oxidosqualene, resulting in ergosterol depletion and toxic squalene accumulation (PubChem: CID 154909).