Fungal β-1,3-glucan synthase

Fungal β-1,3-glucan synthase is a multisubunit enzyme complex located in the plasma membrane of fungal cells, essential for the biosynthesis of β-1,3-glucan, a major polysaccharide component of the fungal cell wall. The core catalytic subunit, known as Fks1 (and its homolog Fks2), utilizes UDP-glucose to elongate β-1,3-glucan chains that provide structural integrity to the fungal cell wall. Its activity is tightly regulated by small GTPases of the Rho family, essential for enzyme activation and cell wall homeostasis. Owing to the absence of β-1,3-glucan synthase in humans and its crucial role in fungal survival, this enzyme is an established, validated therapeutic target for antifungal drugs, mainly the echinocandin class (e.g., caspofungin, micafungin, anidulafungin) and the newer triterpenoid ibrexafungerp, both of which exert fungicidal or fungistatic effects by inhibiting cell wall glucan synthesis. Resistance can emerge due to mutations in FKS1 and FKS2, and the detection of β-1,3-glucan in bodily fluids serves as a biomarker for fungal infection and drug efficacy monitoring.

Other names

β-1,3-glucan synthase1,3-β-D-glucan synthaseFks1 (main catalytic subunit)Fks2 (paralog)GS

Inhibition of β-1,3-glucan synthase activity, leading to loss of cell wall integrity, cell wall stress, and fungal cell death. Noncompetitive inhibition (for some agents) of enzyme activity, resulting in cell wall disruption. Echinocandins and ibrexafungerp bind to the Fks1 subunit and inhibit glucan polymerization essential for cell wall biosynthesis.