Neuraminic acid, biosynthesis

Lucka, L. Krause, M. Danker, K. Reutter, W. Horstkorte, R. Primary structure and expression analysis of human UDP-N-acetyl-glucosamine-2-epimerase/N-acetylmannosamine kinase, the bifimctional enzyme in neuraminic acid biosynthesis. FEBS Lett., 454, 341-344 (1999)... 

The biosynthesis of Kdo and neuraminic acid is known to involve enol-pyruvate phosphate and D-arabinose or 2-acetamido-2-deoxy-D-mannose, respectively. Nothing is known about the biosynthesis of all the other glycu-losonic acids. One interesting problem is, for example, whether the two 5,7-diamino-3,5,7,9-tetradeoxynonulosonic acids are synthesized analogously to neuraminic acid, from a three- and a six-carbon fragment, by modification of neuraminic acid on the sugar nucleotide level, or by a third, less obvious route. 

Figure 1.9 Schematic of the biosynthesis of N-acetyl neuraminic acid and Kdo. The synthetases will have catal5dic machinery for opening the ring forms of the sugar, and an enz5me nucleophile preassociated to attach the phosphoryl group of phosphoenol p5Tuvate (free metaphosphate is not formed).

Biosynthesis of 5-N-acetyl-2-deoxy-2,3-didehydro-neuraminic acid... 

Szabo and his colleagues have prepared 3-deoxy-D-crj f/iro- and U-threo-hcx-2-ulosonic acid 5-phosphate in the ratio 2 1 as illustrated in Scheme 1. The products were isolated in 37 and 23% yield, respectively, as their magnesium salts.In parallel fashion, Russian workers have developed a synthesis of 3-deoxyaldulosonic acids as depicted in Scheme Studies by n.m.r. spectroscopy of ot- and /3-A-acetylneuraminic acid derivatives and determination of /c-i-H-3 e values allowed the conclusion that, in cytidine 5-phospho-iV-acetyl-neuraminic acid, a key intermediate in the biosynthesis of glyconoconjugates, the neuraminic acid moiety has the 3-configuration. ... 

A short review (11 pages, 14 references) on the synthesis and evaluation of mechanism-based inhibitors of Kdo8P synthase has appeared. " A review on the alkaline biocatalysis for the direct biosynthesis of iV-acetyl-D-neuraminic acid (NeuSAc) from iV-acetyl-D-glucosamine has also been written. The syntheses of furanose derivatives of 3-deoxy-D-cryt/iro-2-hexulosonic acid and their 3-bromo and 3-deuterio analogues have been reported. 3-Deoxyoctulosonic acid 16 has been prepared by use of E. coli heptulosonate synthase (Scheme 6). ... 

Schauer, R. (1971) Biosynthesis of N-acetyl-O-acetyl-neuraminic Acid I. Incorporation of... 

In the biosynthesis of A. s., the amino group is supplied by transamination from glutamine. Fructose 6-phosphate is aminated to D-glucosamine 6-phosphate by a hexose-phosphate transaminase. Glucosamine phosphate can then be converted by a transacetylase into the N-acetyl derivative. The latter is isomerized to the 1-phosphate, then activated by reaction with UTP, to form UDP-N-acetylglucosamine, which can be isomerized to UDP-N-acetylgalactosamine. See Muramic acid. Neuraminic acid. 

KDO has chemical properties similar to those of neuraminic acid as it has a carboxylate group, a 3-deoxy group, and a similar biosynthesis (see Chapter 10). The monosaccharide composition, sequence, and linkages, along with the position of attachment of phosphate and ethanolamine pyrophosphate substituted onto the heptose residues of the core polysaccharide have been determined [53-58] and are shown in Fig. 9.16C. The fatty acids in the lipopolysaccharide participate in the formation of a lipid bilayer for the outer membrane. The carbohydrate is hydrophilic and is located on the outer faces of the lipid bilayer membrane. The O-antigen polysaccharides and other capsular polysaccharides are attached to position-4 of the next to last monosaccharide residue, a-D-glucopyranose of the core polysaccharide. 

A-acetyl-mannosamine is an important precursor for the biosynthesis of the nine carbon sugar acid, iV-acetyl-D-neuraminic acid (see section 10.5 and Fig. 10.8A) that is frequently found as a monosaccharide in glycoproteins and glyco-lipids (see Chapter 9). 

Biosynthesis of Eight- and Nine-Carbon Sugars N-Acetyl-D-Neuraminic Acid, N-Acetyl-o-Muramic Acid, and 2-Keto-3-Deoxy-D-Mannooctulosonic Acid (KDO)... 

Figure 10.8. Biosynthesis of sugar acids with eight and nine carbons A, iV-acetyl-D-neuraminic acid B, 2-keto-3-deoxyoctulosonic acid (KDO) C, A acetyl-D-muranic acid.

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. 

Warren, L., and Felsenfeld, H., 1961, N-Acetylmannosamine-6-phosphate and A-acetyl-neuraminic acid -9-phosphate as intermediates in sialic acid biosynthesis, Biochem. Biophys. Res. Comm. 5 185. 

Schauer, R., 1970a, Biosynthesis of A-acetyl-O-neuraminic acid. I. Incorporation of acetate into slices of the submaxillary salivary glands of ox and horse, Z. Physiol. Chem. 351 595. 

Basic ganglioside structure without A/-acetyl neuraminic acid (sialic acid) residues. Intermediate in ganglioside biosynthesis (rat, frog, brain)... 

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