Squalene epoxidase (Trichophyton rubrum) (SE)

Squalene epoxidase (SE) from Trichophyton rubrum is a critical enzyme in the ergosterol biosynthesis pathway, responsible for the conversion of squalene to 2,3-oxidosqualene [1, 5]. As ergosterol is a vital component of the fungal cell membrane, SE serves as a primary target for several classes of antifungal agents, most notably the allylamines such as terbinafine and naftifine, and thiocarbamates like tolnaftate [1, 2, 3]. Inhibition of this enzyme results in a fungicidal effect through two distinct mechanisms: the depletion of ergosterol, which compromises membrane integrity, and the intracellular accumulation of squalene, which exerts direct toxic effects on the fungal cell [3, 6, 9]. Trichophyton rubrum is the most prevalent dermatophyte causing superficial fungal infections, including tinea pedis (athlete's foot) and onychomycosis (nail fungus) [6, 13]. In recent years, the emergence of terbinafine resistance has been increasingly reported, primarily driven by specific point mutations in the SE gene (e.g., L393F, F397L) that reduce drug binding affinity [6, 10, 12]. This resistance poses a significant therapeutic challenge, necessitating the development of alternative treatments or combination therapies [15, 16].

Other names

Squalene monooxygenaseSQLEERG1Squalene 2,3-epoxidase

Non-competitive inhibition of squalene epoxidase, leading to ergosterol depletion and toxic squalene accumulation [1, 3, 8].