Fungal pathogens present a challenge in medicine and agriculture. They also harm ecosystems and threaten biodiversity. The allylamine class of antimycotics targets the enzyme squalene monooxygenase. This enzyme occupies a key position in the sterol biosynthesis pathway in eukaryotes, catalyzing the rate-limiting reaction by introducing an oxygen atom to the squalene substrate converting it to 2,3-oxidosqualene. Currently, terbinafine-the most widely used allylamine-is mostly used for treating superficial fungal infections. The ability to better target this enzyme will have significant implications for human health in the treatment of fungal infections. The human orthologue can also be targeted for cholesterol-lowering therapeutics and in cancer therapies. This review will focus on the structural basis for improving the current therapeutics for fungal squalene monooxygenase.
Keywords: 2,3-oxidosqualene; NB-598; X-ray crystal structures; antifungals; antimycotics; dermatophytes; ergosterol; ergosterol biosynthesis pathway; fungal infections; resistance mutations; squalene; squalene monooxygenase; terbinafine.