Colitose
Encyclopedia
Colitose is a mannose
-derived 3,6-dideoxysugar
produced by certain bacteria. It is a constituent of the lipopolysaccharide
.
bacteria such as Escherichia coli
, Yersinia pseudotuberculosis
, Salmonella enterica
, Vibrio cholerae
, and in marine bacteria such as Pseudoalteromonas sp
. The sugar was first isolated in 1958, and subsequently was enzymatically synthesized in 1962.
The biosynthesis of colitose begins with ColE, a mannose-1-phosphate guanylyltransferase that catalyzes the addition of a GMP
moiety to mannose, yielding GDP-mannose. In the next step, ColB, an NADP
-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
. 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 and O-antigen processing proteins. Further reactions join the O-antigen to the core polysaccharide to form the full lipopolysaccharide
.
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 Escherichia coli
O55 or Salmonella enterica
, respectively, and is commonly referred to as ColD.
s suggests that obscure sugars such as colitose can be incorporated into existing natural-product scaffolds, thereby constructing novel and potentially therapeutic compounds.
Mannose
Mannose is a sugar monomer of the aldohexose series of carbohydrates. Mannose is a C-2 epimer of glucose. It is not part of human metabolism, but is a component of microbial cell walls, and is therefore a target of the immune system and also of antibiotics....
-derived 3,6-dideoxysugar
Deoxy sugar
Deoxy sugars are sugars that have had a hydroxyl group replaced with a hydrogen atom.Examples include:* Deoxyribose * Fucose* Rhamnose-External links:*...
produced by certain bacteria. It is a constituent of the lipopolysaccharide
Lipopolysaccharide
Lipopolysaccharides , also known as lipoglycans, are large molecules consisting of a lipid and a polysaccharide joined by a covalent bond; they are found in the outer membrane of Gram-negative bacteria, act as endotoxins and elicit strong immune responses in animals.-Functions:LPS is the major...
.
Biological role
Colitose is found in the O-antigen of certain Gram-negativeGram-negative
Gram-negative bacteria are bacteria that do not retain crystal violet dye in the Gram staining protocol. In a Gram stain test, a counterstain is added after the crystal violet, coloring all Gram-negative bacteria with a red or pink color...
bacteria such as Escherichia coli
Escherichia coli
Escherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...
, Yersinia pseudotuberculosis
Yersinia pseudotuberculosis
Yersinia pseudotuberculosis is a Gram-negative bacterium that causes Pseudotuberculosis disease in animals; humans occasionally get infected zoonotically, most often through the food-borne route.-Pathogenesis:In animals, Y...
, Salmonella enterica
Salmonella enterica
Salmonella enterica is a rod-shaped flagellated, facultative anaerobic, Gram-negative bacterium, and a member of the genus Salmonella.- Epidemiology :...
, Vibrio cholerae
Vibrio cholerae
Vibrio cholerae is a Gram-negative, comma-shaped bacterium. Some strains of V. cholerae cause the disease cholera. V. cholerae is facultatively anaerobic and has a flagella at one cell pole. V...
, and in marine bacteria such as Pseudoalteromonas sp
Pseudoalteromonas
Pseudoalteromonas is a genus of marine bacterium.-Species:*Pseudoalteromonas agarivorans *Pseudoalteromonas antarctica *Pseudoalteromonas atlantica...
. The sugar was first isolated in 1958, and subsequently was enzymatically synthesized in 1962.
Biosynthesis
Guanosine monophosphate
Guanosine monophosphate, also known as 5'-guanidylic acid or guanylic acid and abbreviated GMP, is a nucleotide that is used as a monomer in RNA. It is an ester of phosphoric acid with the nucleoside guanosine. GMP consists of the phosphate group, the pentose sugar ribose, and the nucleobase...
moiety to mannose, yielding GDP-mannose. In the next step, ColB, an NADP
Nicotinamide adenine dinucleotide
Nicotinamide adenine dinucleotide, abbreviated NAD, is a coenzyme found in all living cells. The compound is a dinucleotide, since it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an adenine base and the other nicotinamide.In metabolism, NAD is involved...
-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
Pyridoxal-phosphate
Pyridoxal-phosphate is a prosthetic group of some enzymes. It is the active form of vitamin B6, which comprises three natural organic compounds, pyridoxal, pyridoxamine and pyridoxine.-Role as a coenzyme:...
-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
Serine Dehydratase or L-Serine Ammonia Lyase is in the ß-family of Pyridoxal Phosphate-dependent enzymes. SDH is found widely in nature, but its structural and chemical properties vary greatly among species. SDH is found in yeast, bacteria, and the cytoplasm of mammalian hepatocytes...
. 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 and O-antigen processing proteins. Further reactions join the O-antigen to the core polysaccharide to form the full lipopolysaccharide
Lipopolysaccharide
Lipopolysaccharides , also known as lipoglycans, are large molecules consisting of a lipid and a polysaccharide joined by a covalent bond; they are found in the outer membrane of Gram-negative bacteria, act as endotoxins and elicit strong immune responses in animals.-Functions:LPS is the major...
.
GDP-4-keto-6-deoxymannose-3-dehydratase (ColD)
ColD is a PLP-dependent enzymeEnzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
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 Escherichia coli
Escherichia coli
Escherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...
O55 or Salmonella enterica
Salmonella enterica
Salmonella enterica is a rod-shaped flagellated, facultative anaerobic, Gram-negative bacterium, and a member of the genus Salmonella.- Epidemiology :...
, respectively, and is commonly referred to as ColD.
Usage in biotechnology
Although the sugar is relatively rare, recent work with glycosyltransferaseGlycosyltransferase
Glycosyltransferases are enzymes that act as a catalyst for the transfer of a monosaccharide unit from an activated nucleotide sugar to a glycosyl acceptor molecule, usually an alcohol....
s suggests that obscure sugars such as colitose can be incorporated into existing natural-product scaffolds, thereby constructing novel and potentially therapeutic compounds.