Structure and biosynthetic mechanisms of galactomannans in filamentous fungi

The cell wall of filamentous fungi is crucial for the physical protection of the cell, the sensing environmental cues, and the expression of virulence. The fungal cell wall consists of a rigid yet flexible three-dimensional network in which structural polysaccharides, such as β-(1 → 3)-glucan and chitin, are intricately intertwined with α-(1 → 3)-glucan, galactosaminogalactan, and galactomannan. Galactomannan is a glycan containing mannose and galactofuranose, the latter of which is a sugar residue absent in humans, and it serves as an important indicator in the clinical diagnosis of invasive pulmonary aspergillosis. Moreover, the biosynthetic pathway of galactomannan is a potential target for novel antifungal drugs. The term galactomannan does not refer to a single molecule but is rather a collective term for structurally distinct fungal-type and O-mannose-type galactomannans. The specific enzymes and precise pathways responsible for the biosynthesis of these glycans have long remained elusive. In this review, we present the current understanding of the supply and transport pathways of sugar nucleotides that are the foundation of galactomannan biosynthesis and describe the functions and three-dimensional protein structures of the key glycosyltransferases responsible for synthesizing fungal-type and O-mannose-type galactomannans, with a focus on our recent discoveries. We also introduce recent findings regarding newly discovered conidia-specific mannan structures and mycelial N-glycan outer chain-like mannan structures. Together, these insights provide future perspectives regarding the development of novel antifungal agents.