(1→6)—β-Glucan Biosynthesis: Potential Targets for Antifungal Drugs

Abstract

The fungal cell wall is a complex dynamic organelle involved in a range of cellular processes including osmotic protection, uptake and secretion of macromolecules, vegetative growth, conjugation, and spore formation (see Peberdy, 1989, for a review). The wall of Saccharomyces cerevisiae determines the yeast cell shape, and is composed of a variety of polymers, including mannoprotein, chitin, and β-glucans. Because some polysaccharides in the fungal cell wall appear to be absent from mammalian cells, components involved in their biosynthesis have long been seen as potential targets for specific antifungal agents. Here we attempt to review the synthesis of one such polymer class, the (1→6)-β — D-glucans, and explore their potential value as a target for antifungals. In the yeast cell wall, β-glucan is an abundant polymer, with the (1→6)-β-glucan component comprising some 20% of the alkali insoluble glucan and some 3% of the dry weight of the yeast cell. The so-called (1→6)- β-D-glucan is a mixed-linked polymer of approximately 140 to 200 glucose residues that are principally joined through linear (1∙6)-β-linkages (Manners et al., 1973b; Boone et al., 1990), but also contain some linear (1→3)linked residues and some 14% (1→3)-branch points.