Trichophyton rubrum squalene epoxidase (ERG1)

Trichophyton rubrum squalene epoxidase is a membrane-bound enzyme that plays a pivotal role in the ergosterol biosynthetic pathway of the dermatophyte fungus Trichophyton rubrum (PubMed: 28842465). It catalyzes the conversion of squalene into 2,3-oxidosqualene, which is a rate-limiting step in the production of ergosterol, a vital component of the fungal cell membrane (UniProt: A0A084IQC5). Because humans utilize a different pathway for cholesterol synthesis and have a distinct squalene epoxidase structure, this enzyme is a highly selective target for antifungal agents (StatPearls: NBK541032). Allylamine drugs, most notably terbinafine, act as non-competitive inhibitors of this enzyme, leading to a deficiency in ergosterol and a lethal accumulation of squalene within the fungal cell (PubChem CID: 154909). Clinically, this target is central to treating common fungal infections such as onychomycosis and tinea pedis, though its efficacy is increasingly threatened by specific point mutations in the ERG1 gene that confer drug resistance (PubMed: 31636071). These mutations, such as Leu393Phe, alter the drug-binding pocket, significantly reducing the binding affinity of allylamines (PubMed: 28842465). Understanding the structural and functional nuances of this enzyme is essential for developing next-generation antifungals that can overcome existing resistance mechanisms. The enzyme's dependence on FAD and NADPH as cofactors further characterizes its role as a monooxygenase within the fungal metabolic network (UniProt: A0A084IQC5).

Other names

Squalene monooxygenaseSqualene 2,3-epoxidaseERG1

Non-competitive inhibition of squalene epoxidase, leading to depletion of ergosterol and accumulation of squalene, which is toxic to the fungal cell (PubMed: 30115761).