Squalene monooxygenase (Candida parapsilosis) (ERG1)

Squalene monooxygenase, encoded by the ERG1 gene, is a critical enzyme in the ergosterol biosynthetic pathway of the opportunistic pathogen Candida parapsilosis. It catalyzes the conversion of squalene to 2,3-oxidosqualene, a rate-limiting step in the production of ergosterol, which is essential for maintaining fungal cell membrane integrity and fluidity (UniProt: A0A0L0NSR5). Inhibition of this enzyme by antifungal agents, particularly allylamines like terbinafine, leads to a dual fungicidal effect: the depletion of ergosterol and the toxic accumulation of squalene within the fungal cell (PubMed: 31659067). While Candida parapsilosis is a common cause of candidemia and hospital-acquired infections, it often exhibits higher minimum inhibitory concentrations (MICs) for certain antifungals compared to other Candida species, making the study of its specific ERG1 enzyme vital for addressing drug resistance (PubMed: 28848236). Mutations in the ERG1 gene have been identified as a primary mechanism of clinical resistance to allylamines in various fungi, highlighting its importance as a therapeutic target (PubMed: 30635408). Understanding the structural and functional nuances of this enzyme in Candida parapsilosis is essential for the development of more effective antifungal strategies.

Other names

Squalene epoxidaseERG1SESqualene,hydrogen-donor:oxygen oxidoreductase (2,3-epoxidizing)

Non-competitive inhibition of squalene monooxygenase, leading to ergosterol depletion and squalene accumulation.