Squalene monooxygenase (Candida spp.) (ERG1)

Squalene monooxygenase, also known as squalene epoxidase, is a vital enzyme in the ergosterol biosynthetic pathway of fungi, including various Candida species (UniProt: P14764). It catalyzes the conversion of squalene into 2,3-oxidosqualene, which is a prerequisite for the formation of ergosterol, the primary sterol in fungal cell membranes (PubMed: 25118326). In Candida species, this enzyme is encoded by the ERG1 gene and serves as a primary target for the allylamine class of antifungal drugs, such as terbinafine and naftifine (StatPearls: NBK545218). The inhibition of squalene monooxygenase leads to a deficiency in ergosterol, compromising membrane integrity, and a concomitant accumulation of squalene, which is toxic to the fungal cell (PubMed: 17075250). This dual mechanism provides a fungicidal effect against many pathogens. Although a human homolog exists, therapeutic agents are significantly more potent against the fungal version, though monitoring for potential side effects like hepatotoxicity remains important in clinical practice (PubChem: CID 154909). Resistance in Candida species can emerge through specific point mutations in the ERG1 gene that reduce drug binding affinity (PubMed: 30139808).

Other names

Squalene epoxidaseSqualene 2,3-epoxidaseSEERG1p

Non-competitive inhibition of squalene monooxygenase, resulting in the depletion of ergosterol and the toxic accumulation of squalene within the fungal cell (PubMed: 17075250).