Beta-1,3-D-glucan synthase catalytic subunit (Fks1)

The fungal beta-1,3-D-glucan synthase catalytic subunit is a critical enzyme complex component responsible for the synthesis of beta-1,3-glucan, the primary structural polysaccharide in the fungal cell wall (UniProt P38631). Encoded primarily by the FKS1 gene (and its paralogs FKS2 and FKS3), this large integral membrane protein catalyzes the transfer of glucose from UDP-glucose to a growing glucan chain and facilitates its translocation to the extracellular space (NIH, 1.4.4). Because mammalian cells lack a cell wall and do not produce beta-1,3-glucan, this enzyme is a highly selective and effective target for antifungal agents (Wikipedia). Echinocandins, such as caspofungin and micafungin, and the triterpenoid ibrexafungerp act as non-competitive inhibitors of this subunit, leading to weakened cell walls, osmotic lysis, and fungal death (NIH, 1.3.1). Clinical resistance to these drugs is often mediated by specific mutations in hotspot regions of the FKS1 or FKS2 genes, which decrease the enzyme's sensitivity to inhibition (NIH, 1.3.5).

Other names

Fks1p1,3-beta-glucan synthase component FKS11,3-beta-D-glucan-UDP glucosyltransferaseGls1Gsc1Cnd1Cwh53Etg1Pbr1

Non-competitive inhibition of the 1,3-beta-D-glucan synthase enzyme, which prevents the synthesis of beta-1,3-glucan, a vital structural component of the fungal cell wall, leading to osmotic instability and cell lysis (NIH, 1.3.1).