Squalene monooxygenase (Candida albicans) (ERG1)

Squalene monooxygenase, also known as squalene epoxidase and encoded by the ERG1 gene in Candida albicans, is a critical enzyme in the ergosterol biosynthetic pathway. It catalyzes the stereospecific epoxidation of squalene to 2,3-oxidosqualene, which is a rate-limiting step in the production of ergosterol. Ergosterol is a primary component of the fungal cell membrane, essential for maintaining its fluidity, permeability, and structural integrity. Because humans synthesize cholesterol instead of ergosterol, this enzyme serves as a highly selective target for antifungal therapy. Drugs such as allylamines (e.g., terbinafine and naftifine) inhibit this enzyme, leading to a dual mechanism of action: the depletion of ergosterol weakens the cell membrane, while the resulting accumulation of squalene is toxic to the fungal cell. Beyond its role in membrane synthesis, squalene monooxygenase is also involved in fungal morphogenesis, specifically the transition from yeast to hyphal forms, which is a key virulence factor in Candida infections.

Other names

Squalene epoxidaseERG1Ergosterol biosynthesis protein 1Squalene monooxygenase ERG1

Inhibition of squalene monooxygenase leads to the depletion of ergosterol and the toxic accumulation of squalene within the fungal cell.