Biosynthesis of the Fungal Cell Wall Polysaccharide Galactomannan Requires Intraluminal GDP-mannose

• Published in: The Journal of biological chemistry Vol. 287; no. 53; pp. 44418 - 44424
• Main Authors: Engel, Jakob, Schmalhorst, Philipp S., Routier, Françoise H.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 28.12.2012; American Society for Biochemistry and Molecular Biology
• Subjects: Aspergillus fumigatus - chemistry; Aspergillus fumigatus - genetics; Aspergillus fumigatus - metabolism; Carbohydrate Biosynthesis; Carrier Proteins - genetics; Cell Wall; Cell Wall - chemistry; Cell Wall - genetics; Cell Wall - metabolism; Fungal Proteins - genetics; Fungal Proteins - metabolism; Fungi; Glycobiology; Glycobiology and Extracellular Matrices; Glycosyl Phosphatidylinositol Anchors; Guanosine Diphosphate Mannose - metabolism; Mannans - biosynthesis; Mannans - chemistry; Molecular Structure; Nucleotide Sugar Transporters; Polysaccharide; Cell Wall; Fungi; Glycobiology; Glycosyl Phosphatidylinositol Anchors; Carbohydrate Biosynthesis; Polysaccharide; Nucleotide Sugar Transporters
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M112.398321

Fungal cell walls frequently contain a polymer of mannose and galactose called galactomannan. In the pathogenic filamentous fungus Aspergillus fumigatus, this polysaccharide is made of a linear mannan backbone with side chains of galactofuran and is anchored to the plasma membrane via a glycosylphosphatidylinositol or is covalently linked to the cell wall. To date, the biosynthesis and significance of this polysaccharide are unknown. The present data demonstrate that deletion of the Golgi UDP-galactofuranose transporter GlfB or the GDP-mannose transporter GmtA leads to the absence of galactofuran or galactomannan, respectively. This indicates that the biosynthesis of galactomannan probably occurs in the lumen of the Golgi apparatus and thus contrasts with the biosynthesis of other fungal cell wall polysaccharides studied to date that takes place at the plasma membrane. Transglycosylation of galactomannan from the membrane to the cell wall is hypothesized because both the cell wall-bound and membrane-bound polysaccharide forms are affected in the generated mutants. Considering the severe growth defect of the A. fumigatus GmtA-deficient mutant, proving this paradigm might provide new targets for antifungal therapy. Understanding the mechanisms of cell wall biogenesis is important for development of antifungal strategies. Biosynthesis of the fungal polysaccharide galactomannan requires import of GDP-mannose into the Golgi apparatus. It differs from the biosynthesis of other fungal cell wall polysaccharides. This provides a new paradigm for cell wall polysaccharide biosynthesis.