title: Pathway of glycine betaine biosynthesis in Aspergillus fumigatus.
abstract: The choline oxidase (CHOA) and betaine aldehyde dehydrogenase (BADH) genes identified in Aspergillus fumigatus are present as a cluster specific for fungal genomes. Biochemical and molecular analyses of this cluster showed that it has very specific biochemical and functional features that make it unique and different from its plant and bacterial homologs. A. fumigatus ChoAp catalyzed the oxidation of choline to glycine betaine with betaine aldehyde as an intermediate and reduced molecular oxygen to hydrogen peroxide using FAD as a cofactor. A. fumigatus Badhp oxidized betaine aldehyde to glycine betaine with reduction of NAD(+) to NADH. Analysis of the AfchoAΔ::HPH and AfbadAΔ::HPH single mutants and the AfchoAΔAfbadAΔ::HPH double mutant showed that AfChoAp is essential for the use of choline as the sole nitrogen, carbon, or carbon and nitrogen source during the germination process. AfChoAp and AfBadAp were localized in the cytosol of germinating conidia and mycelia but were absent from resting conidia. Characterization of the mutant phenotypes showed that glycine betaine in A. fumigatus functions exclusively as a metabolic intermediate in the catabolism of choline and not as a stress protectant. This study in A. fumigatus is the first molecular, cellular, and biochemical characterization of the glycine betaine biosynthetic pathway in the fungal kingdom.
authors.affiliation: Unité des Aspergillus, Institut Pasteur, Paris, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Lambou
authors.forename: Andrea
authors.initials: A
authors.lastname: Pennati
authors.forename: Isabel
authors.initials: I
authors.lastname: Valsecchi
authors.forename: Rui
authors.initials: R
authors.lastname: Tada
authors.forename: Stephen
authors.initials: S
authors.lastname: Sherman
authors.forename: Hajime
authors.initials: H
authors.lastname: Sato
authors.forename: Remi
authors.initials: R
authors.lastname: Beau
authors.forename: Giovanni
authors.initials: G
authors.lastname: Gadda
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Latgé
mesh_terms: D000429:Alcohol Oxidoreductases / Q000235:genetics / Q000378:metabolism; D001232:Aspergillus fumigatus / Q000235:genetics / Q000378:metabolism*; D001622:Betaine / Q000031:analogs & derivatives / Q000378:metabolism*; D050728:Betaine-Aldehyde Dehydrogenase / Q000235:genetics / Q000378:metabolism; D002794:Choline / Q000378:metabolism; D057075:Enzyme Assays; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D007700:Kinetics; D009154:Mutation; D025282:Mycelium / Q000235:genetics / Q000378:metabolism*; D013045:Species Specificity; D013172:Spores, Fungal / Q000235:genetics / Q000378:metabolism*
chemical_list: D005656:Fungal Proteins; D005182:Flavin-Adenine Dinucleotide; D001622:Betaine; C026820:betaine aldehyde; D000429:Alcohol Oxidoreductases; C019888:choline oxidase; D050728:Betaine-Aldehyde Dehydrogenase; D002794:Choline
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