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Structure type: monomer
Trivial name: 2,4-diacetamido-2,4,6-trideoxy-D-mannopyranose, 2,4-diacetamido-2,4,6-trideoxy-b-D-mannopyranose

• Article ID: 3774
  Schoenhofen IC, Vinogradov E, Whitfield DM, Brisson JR, Logan SM "The CMP-legionaminic acid pathway in Campylobacter: biosynthesis involving novel GDP-linked precursors" - Glycobiology 19(7) (2009) 715-725
  

  The sialic acid-like sugar 5,7-diacetamido-3,5,7,9-tetradeoxy-D-glycero-D-galacto-nonulosonic acid, or legionaminic acid, is found as a virulence-associated cell-surface glycoconjugate in the Gram-negative bacteria Legionella pneumophila and Campylobacter coli. L. pneumophila serogroup 1 strains, causative agents of Legionnaire's disease, contain an α2,4-linked homopolymer of legionaminic acid within their lipopolysaccharide O-chains, whereas the gastrointestinal pathogen C. coli modifies its flagellin with this monosaccharide via O-linkage. In this work, we have purified and biochemically characterized eleven candidate biosynthetic enzymes from C. jejuni, thereby fully reconstituting the biosynthesis of legionaminic acid and its CMP-activated form, starting from fructose-6-P. This pathway involves unique GDP-linked intermediates, likely providing a cellular mechanism for differentiating between this and similar UDP-linked pathways, such as UDP-2,4-diacetamido-bacillosamine biosynthesis involved in N-linked protein glycosylation. Importantly, these findings provide a facile method for efficient large-scale synthesis of legionaminic acid, and since legionaminic acid and sialic acid share the same D-glycero-D-galacto absolute configuration, this sugar may now be evaluated for its potential as a sialic acid mimic.

  Campylobacter jejuni, sialic acid, legionaminic acid, flagellin glycosylation, neuraminic aid

  NCBI PubMed ID: 19282391
  Publication DOI: 10.1093/glycob/cwp039
  Journal NLM ID: 9104124
  Publisher: IRL Press at Oxford University Press
  Correspondence: ian.schoenhofen@nrc-cnrc-gc.ca
  Institutions: Institute for Biological Sciences, National Research Council, Ottawa, Ontario, Canada K1A 0R6
  Methods: 13C NMR, 1H NMR, SDS-PAGE, genetic methods, biochemical methods, CE, CE-MS
  
   
  
  Campylobacter jejuni Cj1329
  CSDB ID 24288 (all data & tools)
• Article ID: 4994
  Friedrich V, Janesch B, Windwarder M, Maresch D, Braun ML, Megson ZA, Vinogradov E, Goneau MF, Sharma A, Altmann F, Messner P, Schoenhofen IC, Schäffer C "Tannerella forsythia strains display different cell-surface nonulosonic acids: biosynthetic pathway characterization and first insight into biological implications" - Glycobiology 7(4) (2017) 342-357
  

  Tannerella forsythia is an anaerobic, Gram-negative periodontal pathogen. A unique O-linked oligosaccharide decorates the bacterium's cell surface proteins and was shown to modulate the host immune response. In our study, we investigated the biosynthesis of the nonulosonic acid (NulO) present at the terminal position of this glycan. A bioinformatic analysis of T. forsythia genomes revealed a gene locus for the synthesis of pseudaminic acid (Pse) in the type strain ATCC 43037 while strains FDC 92A2 and UB4 possess a locus for the synthesis of legionaminic acid (Leg) instead. In contrast to the NulO in ATCC 43037, which has been previously identified as a Pse derivative (5-N-acetimidoyl-7-N-glyceroyl-3,5,7,9-tetradeoxy-l-glycero-l-manno-NulO), glycan analysis of strain UB4 performed in this study indicated a 350-Da, possibly N-glycolyl Leg (3,5,7,9-tetradeoxy-d-glycero-d-galacto-NulO) derivative with unknown C5,7 N-acyl moieties. We have expressed, purified and characterized enzymes of both NulO pathways to confirm these genes' functions. Using capillary electrophoresis (CE), CE-mass spectrometry and NMR spectroscopy, our studies revealed that Pse biosynthesis in ATCC 43037 essentially follows the UDP-sugar route described in Helicobacter pylori, while the pathway in strain FDC 92A2 corresponds to Leg biosynthesis in Campylobacter jejuni involving GDP-sugar intermediates. To demonstrate that the NulO biosynthesis enzymes are functional in vivo, we created knockout mutants resulting in glycans lacking the respective NulO. Compared to the wild-type strains, the mutants exhibited significantly reduced biofilm formation on mucin-coated surfaces, suggestive of their involvement in host-pathogen interactions or host survival. This study contributes to understanding possible biological roles of bacterial NulOs.

  Campylobacter jejuni, Helicobacter, Biofilm, biosynthesis pathway, pseudaminic and legionaminic acid, bacterium

  NCBI PubMed ID: 27986835
  Publication DOI: 10.1093/glycob/cww129
  Journal NLM ID: 9104124
  Publisher: IRL Press at Oxford University Press
  Correspondence: christina.schaeffer@boku.ac.at; Ian.Schoenhofen@nrc-cnrc.gc.ca
  Institutions: Department of NanoBiotechnology, NanoGlycobiology Unit, Universität für Bodenkultur Wien, Muthgasse 11, A-1190 Vienna, Austria, Department of Chemistry, Universität für Bodenkultur Wien, Muthgasse 18, A-1190 Vienna, Austria, National Research Council, Human Health Therapeutics Portfolio, 100 Sussex Drive, Ottawa, ON, Canada K1A 0R6, Department of Oral Biology, School of Dental Medicine, University at Buffalo, 311 Foster Hall, 3435 Main St. Buffalo, New York 14214, USA
  Methods: 13C NMR, 1H NMR, PCR, SDS-PAGE, DNA techniques, b-elimination, genetic methods, biochemical methods, CE, CE-MS, bioinformatic analysis, LC-ESI-MS/MS, biofilm assays
  
   
  
  Tannerella forsythia ATCC 43037
  CSDB ID 12088 (all data & tools)