N-acetylmuramic acid

Listowsky and coworkers showed that the c.d. of this sugar derivative is due entirely to lactic acid, and confirmed that this chromophore is in the D configuration for muramic acid. N-Acetylmuramic acid, in which the amino group is replaced by an amido group at C-2, has a c.d. spectrum that is roughly a linear combination of the lactic acid in muramic acid and the amide in 2-acetamido-2-deoxy-D-glucose. This indicates that the amide chromophore and the lactic acid chromophore in N-acetylmuramic acid behave independently. 

The main function of the ester 34 in bacterial cells seems to be its participation in the biosynthesis of the glycopeptide cell-wall polymer. If this process is blocked, there results the accumulation of a high concentration of sugar nucleotide precursors in the cell. A number of these compounds have been isolated the simplest one is the ester of uridine 5 -pyrophosphate with N-acetylmuramic acid [2-acetamido-3-0-(D-l-carboxyethyl)-2-deoxy-D-glucose] (37), first obtained from Staphylococcus aureus cells that had been treated with penicillin7,151 or Gentian Violet.144 An intermediate in the biosynthesis of 37 was isolated and shown to be the 3 -enolpyruvate ether152,153 (38). 

Three of these saccharides have to be N-acetylmuramic acid, and are either A, C, and E, or B, D, and F. The choice is easy, because the hydroxyl group on C-3 of carbohydrate C points toward the cleft and is hydrogen-bonded to the ring-nitrogen atom of L-tryptophan at position No. 63 of the protein core hence, there is no space for the lactoyl side-chain of N-acetylmuramic acid. Consequently, B, D, and F are N-acetylmuramic acid residues, and this identification is consistent with the low-resolution results. The lactoyl side-chains point out of the cleft, so that there is room for a peptide tail, such as occurs in the cross-linking of the cell walls of Micrococcus lysodeikti-cus.Ui... 

The biosynthesis of cell wall peptidoglycan, showing the sites of action of five antibiotics (shaded bars 1 = fosfomycin, 2 = cycloserine, 3 = bacitracin, 4 = vancomycin, 5 = 3-lactam antibiotics). Bactoprenol (BP) is the lipid membrane carrier that transports building blocks across the cytoplasmic membrane M, N-acetylmuramic acid Glc, glucose NAcGIc or G, /V-acetylglucosamine. 

One of the compounds formed from UDP-GlcNAc is UDP-N-acetylmuramic acid. The initial step in its synthesis is an unusual type of displacement reaction on the a-carbon of PEP by the 3-hydroxyl group of the sugar (Eq. 20-6, step a).40410 Inorganic phosphate is... 

Y. A. Knirel, N. A. Paramonov, E. V. Vinogradov, N. K. Kochetkov, Z. Sidorczyk, and K. Zych, 2-Acetamido-4-0-[(S)-l-carboxyethyl]-2-deoxy-D-glucose, a new natural isomer of N-acetylmuramic acid from the O-specific polysaccharide of Proteuspenneri 35, Carbohydr. Res., 259 (1994) cl-c3. 

Figure 3 Schematic representation of the cytoplasmic steps of biosynthesis of UDP-N-acetylmuramic acid pentapeptide in E. coli. UDP-NAcGlc, UDP-N-acetylglucosamine PEP, phosphoenolpyruvate UDP-NAcEPGlc, UDP-N-acetylenolpyruvylglucosamine UDP-NAcMur, UDP-N-acetylmuramic acid meso-DAV, meso-diaminopimelic acid.

The muramyl peptides (MP) of the bacterial cell walls are polymeric chain molecules composed of N-acetylglucosamine and N-acetylmuramic acid, each carrying a peptide side chain and crosslinked with one another (Fig. 8). The N-terminal D-Ala residues of the side chains are bound covalently to the peptide side chains of neighboring polysaccharide chains via pentaglycine units. 

Fig. 1. Catalysis by lysozyme (l,4-/3-iV-acetylmuramidase) of the cleavage of the gly-cosidic linkage between the C-1 of N-acetylmuramic acid (NAM) and the C-4 of N-acetylglucosamine (NAG) in a polymer of NAM and NAG. The vertical broken line shows the point of cleavage.

---