Colitose

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Template:Chembox E number
Colitose
IUPAC name (2S,4S,5S)-2,4,5-trihydroxyhexanal
Identifiers
3D model (JSmol)
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Properties
C6H12O4
Molar mass 148.15708
Except where noted otherwise, data are given for
materials in their standard state
(at 25 °C, 100 kPa)

Infobox disclaimer and references

Colitose is a 3,6-dideoxysugar that has been isolated from the O-antigen of certain Gram-negative bacteria such as Escherichia coli, Yersinia pseudotuberculosis, Salmonella enterica, Vibrio cholerae, and in marine bacteria such as Pseudoalteromonas sp.[1] This sugar has not been isolated from eukaryotes. First isolated in 1958,[2] it was assumed to be an obscure and relatively unimportant monosaccharide. However, recent work with glycosyltransferases suggest that obscure sugars such as colitose can be incorporated into existing natural product scaffolds, thereby constructing novel and potentially therapeutic compounds.[3]

Biosynthesis

The biosynthesis of colitose involves a set of four enzymes: mannose-1-phosphate guanylyltransferase (ColE), GDP-mannose 4,6-dehydratase (ColB), GDP-4-keto-6-deoxymannose-3-dehydratase (ColD), and GDP-L-colitose synthase (ColC)1. These enzymes and intermediates are shown in the image below. For clarity, groups modified by the previous enzymatic step are highlighted in yellow.

File:Pathway1.jpg

The biosynthesis of colitose begins by “tagging” mannose-1-phosphate with a GMP moiety, yielding GDP-mannose. This reaction is carried out by ColE. In the next step, ColB, a short-chain dehydrogenase-reductase enzyme, uses a tightly-bound NADP to first oxidize C-4 and then remove the hydroxyl at C-6. The resulting product, GDP-4-keto-6-deoxymannose, then reacts with ColD, a pyridoxal-5’-phosphate-dependent enzyme, which removes the hydroxyl at C-3. In the final step, the product of ColD, GDP-4-keto-3,6-dideoxymannose, reacts with ColC, which reduces the ketone functionality at C-4 back to an alcohol and inverts the configuration about C-5.[1]

The resulting product, GDP-L-colitose, is then incorporated into the O-antigen by glycosyltransferases and O-antigen processing proteins. Further reactions join the O-antigen to the core polysaccharide to form the full lipopolysaccharide.

References

  1. 1.0 1.1 Cook PD, Thoden JB and Holden HM. "The structure of GDP-4-keto-6-deoxymannose-3-dehydratase: a unique coenzyme B6-dependent enzyme." Protein Science (2006) 15:2093-2106.
  2. Luderitz O, et al. "Colitose, 3-desoxy-L-fucose, a new sugar building block with immunospecific functions in the enodtoxins, lipopolysaccharides, of some Gram-negative bacteria." Biochemistry (1958) 330:193-197.
  3. Zhang C, Thorson JS, et al. "Exploiting the reversibility of natural product glycosyltransferase-catalyzed reactions." Science (2006) 313:1291-1294.

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