The Structure, Biosynthesis, and Function of β-1,6-Glucan in the Fungal Cell Wall.

β-1,6-Glucan is a functionally crucial polysaccharide of the fungal cell wall, although typically less abundant than β-1,3-glucan and chitin, its content, chain length, and branching vary considerably among species. Structurally, it serves as a covalent cross-linker tethering the external mannoprotein layer to the internal β-1,3-glucan-chitin network, contributing to cell wall integrity and plasticity. Biosynthetically, unlike chitin and β-1,3-glucan, which are synthesized by the plasma membrane-associated synthases, β-1,6-glucan biosynthesis depends on a multi-protein cooperative network spanning the endoplasmic reticulum (ER), Golgi, and cell surface, whose core catalytic machinery remains incompletely defined. Genetic and in vitro reconstitution studies have begun to delineate the contributions of ER-resident proteins (Kre5, Big1, Cwh41/Gls1, Rot2/Gls2, and Cne1), Golgi-localized Kre6/Skn1 family members, and cell-surface components (Kre9, Knh1, Kre1, and Kre11). Functionally, its biological roles are established by two complementary lines of evidence, namely enzymatic digestion by endogenous or exogenous β-1,6-glucanases and inactivation of the biosynthetic machinery. Collectively, these studies show that β-1,6-glucan is essential for cell wall architecture, GPI-anchored protein localization, fungal growth, morphogenesis, and virulence, and acts as a potent immunomodulatory molecule at the fungus-host interface. Elucidating its structure, biosynthesis, and function will advance fungal cell wall biology.