The CMP-legionaminic acid pathway in Campylobacter: biosynthesis involving novel GDP-linked precursors

Glycobiology. 2009 Jul;19(7):715-25. doi: 10.1093/glycob/cwp039. Epub 2009 Mar 12.


The sialic acid-like sugar 5,7-diacetamido-3,5,7,9-tetradeoxy-D-glycero-D-galacto-nonulosonic acid, or legion-aminic 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 alpha2,4-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 11 candidate biosynthetic enzymes from Campylobacter 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.

MeSH terms

  • Campylobacter jejuni / metabolism*
  • Cytidine Monophosphate / metabolism*
  • Glucosamine / biosynthesis*
  • Guanosine Diphosphate / biosynthesis*
  • Guanosine Diphosphate / metabolism
  • Sialic Acids / metabolism*


  • 5,7-diacetamido-8-O-acetyl-3,5,7,9-tetradeoxy-glycero-talo-nonulosonic acid
  • Sialic Acids
  • Guanosine Diphosphate
  • Cytidine Monophosphate
  • Glucosamine