title: Overlapping and distinct roles of Aspergillus fumigatus UDP-glucose 4-epimerases in galactose metabolism and the synthesis of galactose-containing cell wall polysaccharides.
abstract: The cell wall of Aspergillus fumigatus contains two galactose-containing polysaccharides, galactomannan and galactosaminogalactan, whose biosynthetic pathways are not well understood. The A. fumigatus genome contains three genes encoding putative UDP-glucose 4-epimerases, uge3, uge4, and uge5. We undertook this study to elucidate the function of these epimerases. We found that uge4 is minimally expressed and is not required for the synthesis of galactose-containing exopolysaccharides or galactose metabolism. Uge5 is the dominant UDP-glucose 4-epimerase in A. fumigatus and is essential for normal growth in galactose-based medium. Uge5 is required for synthesis of the galactofuranose (Galf) component of galactomannan and contributes galactose to the synthesis of galactosaminogalactan. Uge3 can mediate production of both UDP-galactose and UDP-N-acetylgalactosamine (GalNAc) and is required for the production of galactosaminogalactan but not galactomannan. In the absence of Uge5, Uge3 activity is sufficient for growth on galactose and the synthesis of galactosaminogalactan containing lower levels of galactose but not the synthesis of Galf. A double deletion of uge5 and uge3 blocked growth on galactose and synthesis of both Galf and galactosaminogalactan. This study is the first survey of glucose epimerases in A. fumigatus and contributes to our understanding of the role of these enzymes in metabolism and cell wall synthesis.
authors.affiliation: From the Department of Microbiology and Immunology, McGill University, Montréal, Québec H3A 2B4, Canada.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Lee
authors.forename: Fabrice N
authors.initials: FN
authors.lastname: Gravelat
authors.forename: Robert P
authors.initials: RP
authors.lastname: Cerone
authors.forename: Stefanie D
authors.initials: SD
authors.lastname: Baptista
authors.forename: Paolo V
authors.initials: PV
authors.lastname: Campoli
authors.forename: Se-In
authors.initials: SI
authors.lastname: Choe
authors.forename: Ilia
authors.initials: I
authors.lastname: Kravtsov
authors.forename: Evgeny
authors.initials: E
authors.lastname: Vinogradov
authors.forename: Carole
authors.initials: C
authors.lastname: Creuzenet
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.forename: Albert M
authors.initials: AM
authors.lastname: Berghuis
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Latgé
authors.forename: Scott G
authors.initials: SG
authors.lastname: Filler
authors.forename: Thierry
authors.initials: T
authors.lastname: Fontaine
authors.forename: Donald C
authors.initials: DC
authors.lastname: Sheppard
mesh_terms: D001232:Aspergillus fumigatus / Q000235:genetics / Q000378:metabolism*; D002473:Cell Wall / Q000235:genetics / Q000378:metabolism*; D062610:Fungal Polysaccharides / Q000096:biosynthesis* / Q000235:genetics; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D005690:Galactose / Q000235:genetics / Q000378:metabolism*; D014534:UDPglucose 4-Epimerase / Q000235:genetics / Q000378:metabolism*
chemical_list: D062610:Fungal Polysaccharides; D005656:Fungal Proteins; D014534:UDPglucose 4-Epimerase; D005690:Galactose
keywords: Carbohydrate Biosynthesis; Cell Wall; Galactose Metabolism; Glycobiology; Mycology; Polysaccharide