Squalene epoxidase (Trichophyton tonsurans) (SQLE)

Squalene epoxidase is a critical rate-limiting enzyme in the ergosterol biosynthetic pathway of fungi, including the dermatophyte Trichophyton tonsurans. It catalyzes the epoxidation of squalene to 2,3-oxidosqualene, a precursor for ergosterol, which is essential for maintaining fungal cell membrane integrity and fluidity (PubMed: 29437741). This enzyme is the primary therapeutic target for allylamine antifungal drugs like terbinafine. Inhibition of squalene epoxidase leads to a fungicidal effect through two mechanisms: the deficiency of ergosterol and the intracellular accumulation of squalene, which is toxic to the fungus (StatPearls: NBK545218). In recent years, specific point mutations in the SQLE gene of Trichophyton species have been identified as the molecular basis for clinical resistance to terbinafine, posing a significant challenge in treating common skin and scalp infections (PubMed: 32665311).

Other names

Squalene monooxygenaseERG1SE

Non-competitive inhibition of squalene epoxidase, leading to depletion of ergosterol and toxic accumulation of squalene within the fungal cell.