Fungal 1,3-β-D-glucan synthase

Fungal 1,3-β-D-glucan synthase is a membrane-bound glycosyltransferase complex that catalyzes the synthesis of β-1,3-glucan, the principal structural polysaccharide of the fungal cell wall[1][3][5]. This enzyme is absent from mammalian cells, making it an attractive target for antifungal drug development. The core catalytic subunit, typically referred to as Fks1 in yeast, assembles into a large multi-transmembrane complex responsible for polymerizing UDP-glucose into linear β-1,3-glucans and translocating the product across the plasma membrane[1][3][4][5][6]. Its activity is regulated by the small GTPase Rho1 and supporting subunits; loss of function is lethal to most fungi due to cell wall destabilization[3]. Fungal 1,3-β-D-glucan synthase is the established clinical target of echinocandin-class antifungals and triterpenoid agents such as ibrexafungerp, which inhibit polymerization and lead to cell wall disruption and cell death[1][3][5]. The medically relevant mechanism of resistance is via point mutations in the Fks subunits, which reduce drug binding but often come at a fitness cost. β-1,3-D-glucan is also a clinical biomarker for the diagnosis and monitoring of invasive fungal infections[3].

Other names

β-1,3-glucan synthase1,3-β-glucan synthaseGlucan synthaseGSFks1 (catalytic subunit, especially in yeast[1][3])FK506 supersensitive protein 1 (gene name FKS1[3])FKS2 and FKS3 (paralogs in some fungal species[3])

Inhibition of β-1,3-glucan synthesis leading to weakened and osmotically fragile fungal cell wall[1][3][5] Non-competitive or competitive inhibition of the glucan synthase enzyme complex