Lipopolysaccharide biosynthesis

A number of stimuli are known to act as inducers of TNF production (Table 5.10). Bacterial lipopolysaccharide represents the most important inducer, and TNF mediates the pathophysiological effects of this molecule. TNF biosynthesis is regulated by both transcriptional and post-transcriptional mechanisms. Macrophages appear to constitutively express TNF-a mRNA,... 

One of the most impressive findings has been the discovery of lipid intermediates in the biosynthesis of polysaccharides (see Refs. 2 and 465.) At least two structurally different types of these compounds exist the intermediate may be an isoprenoid alcohol ester of the glycosyl pyrophosphate or the analogous derivative of the glycosyl phosphate. Derivatives of the first type are formed by reaction between the sugar nucleotide and the alcohol phosphate, for example, undecaprenyl phosphate (120), which participates in the biosynthesis of Salmonella lipopolysaccharide.466... 

Stuehr, D. J., and Marietta (1985). Mammalian nitrate biosynthesis Mouse macrophages produce nitrite and nitrate in response to Escherichiacoli lipopolysaccharide. Proc. Natl. Acad. Sci. U.S.A. 82, 7738-7742. 

Wagner, D., and Tannenbaum, S. R. (1982). Enhancement of nitrate biosynthesis by Escherichia coli lipopolysaccharide. In Nitrosamines and Human Cancer (P. N. Magee, ed.). Cold Spring Harbor Laboratory, Cold Spring Harbor, New York. 

A brief review of bacterial biosynthesis of phospholipids and lipopolysaccharides. 

M. A. Ghalambor and E. C. Heath, The biosynthesis of cell wall lipopolysaccharide in Escherichia coli, J. Biol. Chem. 241 3222 (1966). 

In bacterial lipopolysaccharides, O-specific chains composed of repeating, or modified repeating, units are linked to a unique oligosaccharide sequence of the core region which is connected to a lipid A fragment serving as a hydrophobic anchor embedded in the bacterial outer-membrane. Biosynthesis of O-specific chains was found to occur independently on formation of other structural fragments of the lipopolysaccharide molecule. Both block and monomeric mechanisms were demonstrated for the biosynthesis of these polymers. 

The 3-deoxy-D-ma/ino-2-octulosonic acid 8-phosphate synthase (KDO synthase or KdoS EC 4.1.2.16) is an enzyme involved in the biosynthesis of the eight-carbon sugar KDO [63], a constituent of the capsular polysaccharides (K-antigens) and outer membrane lipopolysaccharides (LPS, endotoxin) of Gram-negative bacteria [156], as well as of the cell wall of algae and a variety of plants [157], In vivo, the enzyme catalyzes the irreversible addition of 26 to D-arabinose 5-phosphate (Ara5P, 32) to form KDO 8-phosphate 33 [158]. The... 

In Figure 1, the structures of the Ra to Re lipopolysaccharides have been indicated. These incomplete lipopolysaccharides which are devoid of O chains and parts of the core are formed by R mutant strains which are defective in the synthesis of the O chain (Ra) or of the core (Rb-Re) (reviewed by Luderitz et al., 1982). Ra to Re lipopolysaccharides represent intermediates in lipopolysaccharide biosynthesis. They express distinct serological specificities since the respective terminal sugar units act as the main immunodeterminant. The different R lipopolysaccharides and the respective R mutants, therefore, can be differentiated by serological methods. 

H. Brade Chlamydial lipopolysaccharide chemical and antigenic structure, biosynthesis, and medical applications... 

C. R. IT. Raetz Structure, biosynthesis and function of lipopolysaccharide endotoxins potent bacterial activators of innate immunity... 

Fig. 9. Lipopolysaccharide biosynthesis locus of Legionella pneumophila serogroup 1 strain RC1 (OLDA) (taken from Ref. 46 and modified16,44).

UDP-GlcNAc represents the branching point for the bacterial biosynthesis of murein and lipopolysaccharides where secondary nucleotide sugars are involved [329, 358], Starting from fructose-6-P, all enzymes are available as recombinant proteins and enzymatic synthesis of important intermediates seems to be possible. 

Minghetti L, Levi G (1995) Induction of prostanoid biosynthesis by bacterial lipopolysaccharide and isoproterenol in rat microglial cultures. J. Neurochem. 65 2690-2698. 

Keywords Outer membrane Lipopolysaccharide Endotoxin Lipid A LPS biosynthesis... 

Brozek, K.A., Hosaka, K., Robertson, A.D., Raetz, C.R.H. Biosynthesis of lipopolysaccharide in Escherichia coli cytoplasmic enzymes that attach 3-deoxy-D-manno-octulosonic acid to lipid A. J Biol Chem 264 (1989) 6956-6966. 

Marolda, C.L., Vicarioli, J., Valvano, M.A. Wzx proteins involved in biosynthesis of O antigen function in association with the first sugar of the O-specific lipopolysaccharide subunit. Microbiology 150 (2004) 4095 1105. 

Muller-Loennies, S., Lindner, B., Brade, H. Structural analysis of oligosaccharides from lipopolysaccharide (LPS) of Escherichia coli K12 strain W3100 reveals a link between inner and outer core LPS biosynthesis. J Biol Chem 278 (2003) 34090-34101. 

Schnaitman, C.A., Klena, J.D. Genetics of lipopolysaccharide biosynthesis in enteric bacteria. Microbiol Rev 57 (1993) 655-682. 

Wang, X., Ribeiro, A.A., Guan, Z., McGrath, S.C., Cotter, R.J., Raetz, C.R. Structure and biosynthesis of free lipid A molecules that replace lipopolysaccharide in Francisella tularensis subsp. novicida. Biochemistry 45 (2006b) 14427-14440. 

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