A -Acetyl-D-neuraminic acid

A -Acetyl-D-neuraminic acid (NeuNAc), a sialic acid... 

Tabata, K., Koizumi, S., Endo, T. and Ozaki, A., Production of A-acetyl-D-neuraminic acid by coupling bacteria expressing N-acetyl-o-glucosamine 2-epimerase and N-acetyl-o-neuraminic acid synthetase. Enzyme Microb. Technol. 2002, 30, 327-333. 

D-lduronic acid A/-glycolyl-D-neuraminic acid A/-acetyl-D-neuraminic acid... 

The second family of A-linked oligosaccharides are called the lactosamine family in which the D-mannose residues of the core pentasaccharide are substituted 1 2 by lactosamine, which is a lactose analogue with A-acetyl-D-glucosamine substituted for D-glucopyranose at the reducing-end of lactose. The lactosamine is frequently substituted by A-acetyl-D-neu-raminic acid (for the structure of A-acetyl-D-neuraminic acid, see the monomer residue in colominic acid,0 Sect. 8.2 andO Fig. 7) linked 2 3 or 2 6 [142,143]. The third family has a mixed structure of the high mannose and lactosamine families [144,145,146,147]. 

Glycosides of 5-A-acetyl-D-neuraminic acid can be synthesized using glycosyl halide derivatives with silver salts of polymeric carboxylic acids, e.g. polymaleic acid, as catalysts. 

Keratan sulfate is the most heterogeneous of the glycosaminoglycans in that the sulfate content is variable, and it contains small amounts of L-fucose, D-mannose, and A-acetyl-D-neuraminic acid residues [130]. Keratan sulfate proteoglycan is found in the cornea, on the surface of erythrocytes, in cartilage, and in bone. 

Neisseria meningitidis is a pathogen that causes meningitis in humans. It has an unusual capsular homopolysaccharide that is composed of A -acetyl-D-neuraminic acid. The monosaccharide residue has nine carbons (see Fig. 6.20A). It makes up a family of sugar acids called sialic acids that are N- and 0-substituted derivatives (see Chapter 9). The sialic acids are widely distributed and are primarily found at the ends of the oligosaccharide chains attached to glycoproteins that are especially prevalent in bovine and ovine submaxillary mucins, erythrocytes, and nerve tissues. A -acetyl-D-neuraminic acid is biosynthesized by an aldol condensation of pyruvic acid with N-acetyl-D-mannosamine (see Chapter 10). 

N meningitidis (sero group B) and E, coli K1 both have capsular polysaccharides of poly(A -acetyl-D-neuraminic acid) linked 2 —> 8 [193], and both cause meningitis in humans. There is evidence that the polysaccharide is responsible for the infection of tissues [194], possibly by specific cell recognition. The polysaccharide is known as colominic acid (see Fig. 6.20B for the structure). 

Figure 6.20. Structures of A, A -acetyl-D-neuraminic acid B, 2,8-colominic acid C, 2,9-colominic acid D, 2,8/2,9-altemating colominic acid E, 2,8-colominic acid 1,9-polylac-tone.

A -acetyl-D-neuraminic acid is biosynthesized from A -acetyl-D-mannosamine and phosphoenol pyruvate, catalyzed by N-acetyl-D-neuraminic acid synthase. The first step involves the addition of an electron pair from the double bond of the phosphoenol pyruvate to the aldehyde group to give an aldol-type condensation (see Fig. 10.8A). The product is the nine-carbon sugar acid, A -acetyl-D-neuraminic acid [23]. In some instances the enzyme requires A-acetyl-D-mannosamine-6-phosphate as the substrate and forms A-acetyl-D-neuraminic acid-9-phosphate. Various hydroxyl groups on C-4, -7, -8, and -9 can be acetylated by specific acetyl transferases using acetyl CoAas the donor. KDO (2-keto-3-deoxy-D-mannooctulosonic acid) is biosynthesized by a very similar condensation between D-arabinose-5-phosphate and pyruvic acid, catalyzed by KDO synthase (see Fig. 10.8B) [24]. 

The biosynthesis of poly-2 -> 8 or -2 9-(A-acetyl-D-neuraminic acid) capsular polysaccharide (colominic acid) from E. coli or N. meningitidis (see Chapter 6, Fig. 6.20 for the structures) has also been shown to involve a polyprenol phos-phoryl A-acetyl-D-neuraminic acid lipid intermediate formed from CMP-NeuNAc [67,68]. This is an example of the biosynthesis of a homopolysaccharide that requires a polyprenol phosphate coenzyme lipid carrier. 

Ferrero, M.A., Reglero, A., Fernandez-Lopez, M., Ordas, R., and Rodriguez-Aparicio, L.B. A -Acetyl-D-neuraminic acid lyase generates the sialic acid for colominic acid biosynthesis in Escherichia coli Kl. Biochem. J. (1996)3/7, 157-165. 

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