Colitose is a

mannose Mannose is a sugar monomer of the aldohexose series of carbohydrates. It is a C-2 epimer of glucose. Mannose is important in human metabolism, especially in the glycosylation of certain proteins. Several congenital disorders of glycosylation ...

-derived 3,6-dideoxysugar produced by certain bacteria. It is a constituent of the

lipopolysaccharide Lipopolysaccharides (LPS) are large molecules consisting of a lipid and a polysaccharide that are bacterial toxins. They are composed of an O-antigen, an outer core, and an inner core all joined by a covalent bond, and are found in the outer m ...

. It is the

enantiomer In chemistry, an enantiomer ( /ɪˈnænti.əmər, ɛ-, -oʊ-/ ''ih-NAN-tee-ə-mər''; from Ancient Greek ἐνάντιος ''(enántios)'' 'opposite', and μέρος ''(méros)'' 'part') – also called optical isomer, antipode, or optical ant ...

abequose Abequose is a hexose and a 3,6-dideoxysugar. It is a constituent of the in O‐specific chains in lipopolysaccharides that occur in certain serotypes of ''Salmonella'' and ''Citrobacter'' bacteria. It is the enantiomer In chemistry, an enant ...

Biological role

Colitose is found in the O-antigen of certain

Gram-negative Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wall ...

bacteria such as ''

Escherichia coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escher ...

'', ''

Yersinia pseudotuberculosis ''Yersinia pseudotuberculosis'' is a Gram-negative bacterium that causes Far East scarlet-like fever in humans, who occasionally get infected zoonotically, most often through the food-borne route. Animals are also infected by ''Y. pseudotuberc ...

'', ''

Salmonella enterica ''Salmonella enterica'' (formerly ''Salmonella choleraesuis'') is a rod-headed, flagellate, facultative anaerobic, Gram-negative bacterium and a species of the genus ''Salmonella''. A number of its serovars are serious human pathogens. Epidemi ...

'', ''

Vibrio cholerae ''Vibrio cholerae'' is a species of Gram-negative, facultative anaerobe and comma-shaped bacteria. The bacteria naturally live in brackish or saltwater where they attach themselves easily to the chitin-containing shells of crabs, shrimps, and oth ...

'', and in marine bacteria such as ''Pseudoalteromonas sp''. The sugar was first isolated in 1958, and subsequently was enzymatically synthesized in 1962.

Biosynthesis

The biosynthesis of colitose begins with ColE, a mannose-1-phosphate guanylyltransferase that catalyzes the addition of a

GMP GMP may refer to: Finance and economics * Gross metropolitan product * Guaranteed maximum price * Guaranteed Minimum Pension Science and technology * GNU Multiple Precision Arithmetic Library, a software library * Granulocyte-macrophage progenito ...

moiety to mannose, yielding

GDP-mannose Guanosine diphosphate mannose or GDP-mannose is a nucleotide sugar that is a substrate for glycosyltransferase reactions in metabolism. This compound is a substrate for enzymes called mannosyltransferases. Known as donor of activated mannose in al ...

. In the next step, ColB, an

NADP Nicotinamide adenine dinucleotide phosphate, abbreviated NADP or, in older notation, TPN (triphosphopyridine nucleotide), is a cofactor used in anabolic reactions, such as the Calvin cycle and lipid and nucleic acid syntheses, which require NAD ...

-dependent short-chain dehydrogenase-reductase enzyme, catalyzes the oxidation at C-4 and the removal of the hydroxyl group at C-6. The resulting product, GDP-4-keto-6-deoxymannose, then reacts with the PLP-dependent enzyme GDP-4-keto-6-deoxymannose-3-dehydratase (ColD), which removes the hydroxyl at C-3 in a manner similar to that of

serine dehydratase Serine dehydratase or L-serine ammonia lyase (SDH) is in the β-family of pyridoxal phosphate-dependent (PLP) enzymes. SDH is found widely in nature, but its structural and properties vary among species. SDH is found in yeast, bacteria, and the ...

. 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. The resulting product, GDP-L-colitose, is then incorporated into the O-antigen by

glycosyltransferases Glycosyltransferases (GTFs, Gtfs) are enzymes ( EC 2.4) that establish natural glycosidic linkages. They catalyze the transfer of saccharide moieties from an activated nucleotide sugar (also known as the " glycosyl donor") to a nucleophilic gly ...

and ''O''-antigen processing proteins. Further reactions join the O-antigen to the core polysaccharide to form the full

GDP-4-keto-6-deoxymannose-3-dehydratase (ColD)

ColD is a PLP-dependent

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

responsible for the removal of the C-3' hydroxyl group during the biosynthesis of GDP-colitose. It is a product of the ''Wbdk'' or ''ColD'' genes in ''

'' O55 or ''

'', respectively, and is commonly referred to as ColD.

Usage in biotechnology

Although the sugar is relatively rare, recent work with

glycosyltransferase Glycosyltransferases (GTFs, Gtfs) are enzymes ( EC 2.4) that establish natural glycosidic linkages. They catalyze the transfer of saccharide moieties from an activated nucleotide sugar (also known as the "glycosyl donor") to a nucleophilic glycos ...

s suggests that obscure sugars such as colitose can be incorporated into existing natural-product scaffolds, thereby constructing novel and potentially therapeutic compounds.

References

{{reflist Deoxy sugars Aldohexoses