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

Fungal 1,3-beta-glucan synthase is a multi-subunit enzyme complex located in the plasma membrane that is essential for the synthesis of 1,3-beta-D-glucan, the primary structural polysaccharide of the fungal cell wall [8, 13]. The complex typically consists of a catalytic subunit, encoded by the FKS gene family (e.g., Fks1p, Fks2p), and a regulatory subunit, the small GTPase Rho1p [8, 16]. By utilizing UDP-glucose as a substrate, the enzyme polymerizes glucose units into linear chains that provide mechanical strength and osmotic protection to the fungal cell [2, 14]. Because mammalian cells lack a cell wall and this specific enzyme, it serves as a highly selective target for antifungal therapy [9]. Drugs such as echinocandins (e.g., caspofungin) and triterpenoids (e.g., ibrexafungerp) inhibit this enzyme non-competitively, leading to cell wall depletion, osmotic instability, and eventual cell lysis [1, 3, 17]. This target is clinically significant for treating invasive fungal infections like candidiasis and aspergillosis [1, 9]. However, resistance can emerge through mutations in hotspot regions of the FKS subunits, which reduce drug affinity [1, 4]. Monitoring of (1,3)-beta-D-glucan levels in the blood is a common biomarker used to diagnose infections and assess the efficacy of drugs targeting this enzyme [19, 20].

Other names

1,3-beta-D-glucan synthaseUDP-glucose 1,3-beta-D-glucan beta-D-glucosyltransferaseFungal glucan synthaseFks1pFks2pFks3pCallose synthase

Non-competitive inhibition of the catalytic subunit (Fks) of the 1,3-beta-D-glucan synthase complex, disrupting the synthesis of beta-1,3-glucan polymers in the fungal cell wall.