Lipopolysaccharides synthesis

The occurrence of this group of sugar nucleotides is limited mainly to the cells of Gram-negative bacteria. Those bacterial mutants defective in lipopolysaccharide synthesis are useful for preparative isolation of such esters, as the concentration of sugar nucleotides in normal cells is very low. 

In vivo measurements of lipopolysaccharide synthesis in E. coli B have indicated that two nanomoles of KDO must be synthesized per minute per mg of protein in order to meet the cellular requirement for LPS synthesis under the normal conditions of growth on glucose-minimal medium (27). We have measured the specific activities of the enzymes involved in KDO synthesis in crude extracts of E. coli B including those enzymes responsible for the synthesis of D-ribulose-5-phosphate, the precursor of D-arabinose-5-phosphate. D-Ribulose-5-phosphate is a key intermediate in carbohydrate metabolism as shown in Figure 2, since it is the direct precursor of both D-ribose-5-phosphate and D-arabinose-5-phosphate... 

R Goldman, W Kohlbrenner, P Lartey, A Pernet. Antibacterial agents specifically inhibiting lipopolysaccharide synthesis. Nature 329 162-164, 1987. 

Cava, J.R., Tao, H., Noel, K.D. Mapping of complementation groups within a Rhizobium legu-minosarum CFN42 chromosomal region required for lipopolysaccharide synthesis. Mol Gen Genetics 221 (1990) 125-128. 

Gram-positive bacteria contain a rigid peptidoglycan cell wall surrounding the cytoplasmic membrane. Gram-negative bacteria contain an additional third, outer layer. This wall is a complex structure with lipoproteins and lipopolysaccharides. Synthesis of two outer walls from different bacterial cells is described in this concept screen ... 

Peptidoglycan Assembly Lipopolysaccharide Synthesis (in Salmonella and Related Genera)... 

Lipopolysaccharide synthesis occurs on the inner membrane from which the molecule must be transferred to the outer face of the outer membrane. This occurs at specific membrane sites generally where the two membranes adhere to each other. 

FIGURE 8.18 Dolichol phosphate is an initiation point for the synthesis of carbohydrate polymers in animals. The analogous alcohol in bacterial systems, undecaprenol, also known as bactoprenol, consists of 11 isoprene units. Undecaprenyl phosphate delivers sugars from the cytoplasm for the synthesis of cell wall components such as peptidoglycans, lipopolysaccharides, and glycoproteins. Polyprenyl compounds also serve as the side chains of vitamin K, the ubiquinones, plastoquinones, and tocopherols (such as vitamin E). 

Z8. Zuckerman, S. H., Shellhaas, J., and Butler, L. D., Differential regulation of lipopolysaccharide-induced interleukin I and tumor necrosis factor synthesis Effects of endogenous and exogenous glucocorticoids and the role of the pituitary-adrenal axis. Eur. J. Immunol. 19,301-305 (1989). 

Wollenwebcr, H.-W., and Morrison, D.C. (1985) Synthesis and biochemical characterization of a pho-toactivatable, iodinatable, cleavable bacterial lipopolysaccharide derivative. J. Biol. Chem. 260, 15068-15074. 

Some examples of transformations involving carbonyl ylides are listed in Table 4.20. Entry 1 illustrates the conversion of P-acyloxy-a-diazoesters into a-acyloxyacrylates by ring fission of a cyclic carbonyl ylide [978]. This reaction has been used for the synthesis of the natural aldonic acid KDO (3-deoxy-Z)-manno-2-octulosonic acid), which is an essential component of the cell wall lipopolysaccharide of gram-negative bacteria (Figure 4.15). 

Regioselective oxidation by brominolysis of dioxastannolane obtained from methyl / -L-ara-binopyranoside made it possible to accomplish (after subsequent oximation and reduction) a facile synthesis of 4-amino-4-deoxy-L-arabinose, an amino-sugar found in lipopolysaccharides of some Salmonella R. mutant strains <83CPB3778>. 

The occurrence of 3-deoxy-D-manno-octulosonic acid in lipopoly-saccharides has prompted its synthesis,537 together with the D-gal-octo158 and the D-gluco analogs.157 Although gas-liquid chromatography was successfully used to analyze the products of these syntheses, it has been reported that methanolysis of a bacterial endotoxin lipopolysaccharide failed to yield 3-deoxy-D-manno-octulosonic acid, presumably because of the lability of the latter to acid.381 However, Kasai and Nowotny have reported four peaks for the O-trimethylsilyl derivatives of 3-deoxy-D-manno-octulosonic acid obtained by methanolysis of the glycolipid from a Salmonella minnesota mutant.538 Reduced 3-deoxy-D-manno-octulosonic acid and its methyl ester have also been analyzed successfully as their acetates.339,539... 

Lipopolysaccharide had no effect on the protein synthesis ([ HJleucine incorporation) of HC cultured alone. A number of studies concluded that this decrease in protein synthesis was not due to a single cytokine, eicosanoid, or oxygen radical (West et al., 1989). Also, the activity could not be transferred in conditioned supernatant for KC stimulated with LPS alone. However, when... 

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