Disease relevance of 2-dehydro-3-deoxy-D-octonate

• 3-Deoxy-D-manno-oct-2-ulosonic acid (Kdo) transferase (WaaA) and kdo kinase (KdkA) of Haemophilus influenzae are both required to complement a waaA knockout mutation of Escherichia coli [1].
• The conserved Klebsiella outer core contains the unusual trisaccharide 3-deoxy-d-manno-oct-2-ulosonic acid (Kdo)-(2,6)-GlcN-(1,4)-GalUA [2].
• Yersinia pestis YrbH is a multifunctional protein required for both 3-deoxy-D-manno-oct-2-ulosonic acid biosynthesis and biofilm formation [3].
• By using isolated LPS of Re mutants of Escherichia coli, Salmonella enterica serovar Minnesota, and recombinants expressing the 3-deoxy-D-manno-oct-2-ulosonic acid (Kdo) transferase gene kdtA of C. trachomatis, MAb CP-33 was shown to require for binding the presence of the genus-specific trisaccharide epitope alphaKdo(2-->8)alphaKdo(2-->4)alphaKdo [4].
• However, Cps5D had high homology with KdsA proteins (3-deoxy-D-manno-2-octulosonic acid 8-phosphate synthetase) from other gram-negative bacteria [5].

High impact information on 2-dehydro-3-deoxy-D-octonate

• However, all synthetic derivatives of 3-deoxy-D-manno-2-octulosonic acid (KDO) used in this study failed to induce IL 1 production by both mouse macrophages and human monocytes [6].
• Arabinose 5-phosphate isomerase (API), encoded by Y. pestis yrbH, catalyses the conversion of ribulose 5-phosphate into arabinose 5-phosphate (A5P), the first committed step in the 3-deoxy-D-manno-oct-2-ulosonic acid (Kdo) biosynthesis pathway [3].
• Here we have demonstrated that the fix-23 loci, which compensate for exo mutations during symbiotic nodule development, are involved in the production of a novel polysaccharide that is rich in 3-deoxy-D-manno-2-octulosonic acid (Kdo) but is not the classical LPS [7].
• Roles of 3-deoxy-D-manno-2-octulosonic acid transferase from Moraxella catarrhalis in lipooligosaccharide biosynthesis and virulence [8].
• Here, a kdtA gene encoding 3-deoxy-D-manno-2-octulosonic acid (Kdo) transferase, which is responsible for adding Kdo residues to the lipid A portion of the LOS, was identified by transposon mutagenesis and construction of an isogenic kdtA mutant in strain O35E [8].

Chemical compound and disease context of 2-dehydro-3-deoxy-D-octonate

• Lipopolysaccharide components 3-deoxy-D-manno-2-octulosonic acid and L-glycero-D-manno-heptose were detected in hydrolysates from whole cells of Neisseria elongata by gas-liquid chromatography [9].
• We recently identified a constitutively expressed exopolysaccharide of Burkholderia pseudomallei which is composed of a unique linear tetrasaccharide repeating unit consisting of three galactose residues and one 3-deoxy-D-manno-2-octulosonic acid residue [10].
• Sinorhizobium meliloti strain 1021 produces a low-molecular-mass capsular polysaccharide that is a homopolymer of 3-deoxy-D-manno-oct-2-ulosonic acid harboring a phospholipid anchor [11].
• Methylation analysis of the heptose/3-deoxy-D-manno-2-octulosonic acid region (inner core) of the lipopolysaccharide from Salmonella minnesota rough mutants [12].
• Empirical 13C-n.m.r.-correlations between the Escherichia coli K 13 and LP 1092 capsular polysaccharides and model oligosaccharides containing D-ribose and 3-deoxy-D-manno-2-octulosonic acid [13].

Biological context of 2-dehydro-3-deoxy-D-octonate

• Substitution pattern of 3-deoxy-D-manno-oct-2-ulosonic acid in bacterial lipopolysaccharides investigated by methylation analysis of whole LPS [14].
• After mild acid hydrolysis of the LPS, a heptasaccharide was isolated and identified by chemical analyses, GLC-MS, FABMS, and NMR spectroscopy as follows: [carbohydrate structure: see text] where L-alpha-D-Hep stands for L-glycero-alpha-D-manno-heptose, Ko for D-glycero-D-talo-oct-2-ulosonic acid, and Kdo for 3-deoxy-D-manno-oct-2-ulosonic acid [15].
• The genes encoding the 3-deoxy-D-manno-oct-2-ulosonic acid (Kdo) transferase (waaA) and heptosyltransferases I (waaC) and II (waaF) in Klebsiella pneumoniae were cloned from a DNA library by functional complementation of corresponding Escherichia coli and Salmonella enterica mutants [16].

Anatomical context of 2-dehydro-3-deoxy-D-octonate

• A synthetic analog of the 3-deoxy-D-manno-2-octulosonic acid disaccharide moiety of rough-type endotoxins does not bind to mouse peritoneal macrophages and human monocytes [17].
• 3-Deoxy-D-manno-2-octulosonic acid was well separated from other cell components as the O-methyloxime acetate derivative [9].
• We previously showed the importance of the 3-deoxy-D-manno-2-octulosonic acid (KDO) residue in endotoxins (lipopolysaccharides, LPS) for the induction of the synthesis and release of interleukin-1 (IL-1) by human monocytes [18].
• In this context, we have investigated the synthesis of N-acetylneuraminic acid (Neu5Ac) in the cytosol of plants by either the re-routing of the endogenous 3-deoxy-d-manno-2-octulosonic acid (Kdo) biosynthetic pathway or the expression of microbial Neu5Ac-synthesizing enzymes [19].

Associations of 2-dehydro-3-deoxy-D-octonate with other chemical compounds

• Polyacrylamide gel electrophoresis, nuclear magnetic resonance spectrometry, and gas chromatography analyses showed that both of these bacterial species produce unique polysaccharides that contain a high proportion of 3-deoxy-D-manno-2-octulosonic acid (Kdo) [20].
• Component sugar analysis indicated that PG-2' contained 2-Me-Fuc, 2-Me-Xyl, apiose (Api), aceric acid (AceA), 3-deoxy-D-lyxo-heptulosaric acid (Dha), and 3-deoxy-D-manno-2-octulosonic acid (Kdo) in addition to Rha, Fuc, Ara, Xyl, Man, Gal, Glc, GalA, and GlcA [21].

Gene context of 2-dehydro-3-deoxy-D-octonate

• Aquifex aeolicus 3-deoxy-D-manno-2-octulosonic acid 8-phosphate synthase: a new class of KDO 8-P synthase [22]?
• Design and synthesis of peptide derivatives of a 3-deoxy-D-manno-2-octulosonic acid (KDO) analogue as novel antibacterial agents acting upon lipopolysaccharide biosynthesis [23].
• A bacteriophage growing on Escherichia coli K13, K20, and K23 strains carries a glycanase that catalyzes the hydrolytic cleavage of the beta-ketopyranosidic linkages of 3-deoxy-D-manno-2-octulosonic acid (KDO) in the respective capsular polysaccharides [24].
• Partial structures of enterobacterial lipopolysaccharides (LPS) of the Rechemotype, consisting of lipid A and 3-deoxy-D-manno-2-octulosonic acid (Kdo), as well as oligosaccharides and derivative of Kdo were synthesized and used to characterize the epitope specificity of monoclonal antibodies against Re-mutant LPS [25].
• In other parameters such as acyl chain melting behaviour, antibody binding, activity in the Limulus lysate assay, and partially the binding of 3-deoxy-D-manno-oct-2-ulosonic acid transferase, strong deviations from the properties of the phosphorylated compounds were observed [26].

Analytical, diagnostic and therapeutic context of 2-dehydro-3-deoxy-D-octonate

• In our MALDI mass spectra, besides the [M--H](-) ions, abundant ions originating from the cleavage between the 3-deoxy-D-manno-oct-2-ulosonic acid (Kdo) unit and the lipid A moiety are always present, giving important pieces of information about the structure of the molecules analyzed [27].
• The binding specificity of MAb E1 was characterized by direct and inhibition enzyme immunoassays, using natural LPSs from different strains and chemotypes, and synthetic analogs of LPS substructure of the 3-deoxy-D-manno-2-octulosonic acid (Kdo) and Lipid A regions [28].

References