1,3-beta-D-glucan synthase (GS)

Fungal 1,3-beta-D-glucan synthase is a membrane-bound enzyme complex essential for the biosynthesis of 1,3-beta-D-glucan, the primary structural component of the fungal cell wall (1.3.1, 1.3.5). The complex typically consists of a catalytic subunit, encoded by the FKS gene family (e.g., Fks1p, Fks2p), and a regulatory subunit, the Rho1 GTPase (1.3.1). By polymerizing UDP-glucose into long glucan chains, the enzyme provides the mechanical strength and osmotic stability required for fungal cell integrity and growth (1.1.1, 1.4.1). Because 1,3-beta-D-glucan is absent in mammalian cells, this enzyme serves as a highly selective target for antifungal therapy (1.4.1, 1.5.3). Clinically used inhibitors include the echinocandin class, such as caspofungin and micafungin, and the triterpenoid ibrexafungerp (1.4.2, 1.5.1). Inhibition of the enzyme leads to a weakened cell wall, resulting in osmotic lysis and fungal death, particularly in Candida species (1.1.1, 1.4.3). Resistance to these drugs often arises through specific point mutations in the "hot spot" regions of the FKS subunits, which decrease the enzyme's sensitivity to the inhibitors (1.2.1, 1.4.2).

Other names

Fungal-beta-D-glucan synthase1,3-beta-glucan synthaseFks1pFks2pFks3pUDP-glucose beta(1,3)-D-glucan beta(3)-D-glucosyltransferaseCallose synthaseParamylon synthetase

Non-competitive inhibition of the catalytic subunit (Fks) of the 1,3-beta-D-glucan synthase complex, preventing the polymerization of UDP-glucose into 1,3-beta-D-glucan chains and leading to fungal cell wall disruption and osmotic lysis.