Squalene monooxygenase (Trichophyton rubrum) (SQLE)

Squalene monooxygenase (also known as squalene epoxidase) is a critical rate-limiting enzyme in the ergosterol biosynthetic pathway of the dermatophyte fungus Trichophyton rubrum [1, 2]. It catalyzes the stereospecific conversion of squalene to 2,3-oxidosqualene, a process requiring NADPH and FAD as cofactors [1, 2]. This enzyme serves as the primary therapeutic target for the allylamine class of antifungal agents, including terbinafine and naftifine, which are standard treatments for superficial fungal infections such as tinea pedis (athlete's foot) and onychomycosis (nail fungus) [3, 4]. The inhibition of squalene monooxygenase results in a dual antifungal effect: the depletion of ergosterol, which is essential for maintaining fungal cell membrane integrity and fluidity, and the intracellular accumulation of squalene, which is toxic to the fungus and leads to cell death [3, 6]. Although resistance was historically rare, emerging clinical evidence has identified specific point mutations in the T. rubrum SQLE gene, such as L393F and F397L, that significantly reduce drug binding affinity and lead to treatment failure [7, 9]. Understanding the structural and functional characteristics of this enzyme is vital for developing next-generation antifungals that can overcome these resistance mechanisms [3, 10].

Other names

Squalene epoxidaseErg1SESQLE

Non-competitive inhibition of squalene epoxidase leading to ergosterol depletion and toxic squalene accumulation [1, 3, 6].