1,3-β-Glucan synthase enzyme complex (GS)

The 1,3-β-glucan synthase enzyme complex is a multi-protein, membrane-embedded enzyme found in fungi, responsible for the biosynthesis of β-1,3-glucan, the principal structural polysaccharide of the fungal cell wall. Its core consists of a catalytic glycosyltransferase subunit (FKS1, FKS2, or FKS3 in yeast) that uses UDP-glucose as substrate to elongate β-1,3-glucan chains, and a regulatory subunit (Rho1, a small GTPase). This enzyme is essential for fungal viability, as it provides cell wall rigidity and resistance to environmental stresses. Because humans do not have β-1,3-glucan in their cells, this enzyme is a prime target for antifungal drugs—most notably, echinocandin-class antifungals and ibrexafungerp—which inhibit the synthase and disrupt fungal cell wall integrity, leading to cell lysis. The complex’s catalytic mechanisms, structure (recently elucidated by cryo-EM), and the emergence of resistance due to FKS1 mutations are intensively studied in antifungal research.

Other names

1,3-β-glucan synthaseβ-glucan synthaseFKS complexFks1/2/3 complexβ-1,3-glucan synthase complexGS complexFungal glucan synthaseβ-d-glucan synthaseFks1-Rho1 complex

Inhibition of β-1,3-glucan synthesis: Echinocandins and ibrexafungerp bind GS, preventing β-1,3-glucan formation and resulting in defective fungal cell walls and cell death