Murein biosynthesis

The first steps of murein biosynthesis take place in the cytoplasm, whereas the two final steps occur at the inner and outer face of the cytoplasmic membrane, respectively [38]. This may also be true for the pseudomurein, according to a tentative scheme of the biosynthesis of pseudomurein (Fig. 4) [39-43], proposed on the basis of the structure of putative precursors isolated from cell extracts. 

It appears highly likely that the anti-pseudomonas -lactam antibiotics, like other j3-lactam antibiotics, interfere with murein biosynthesis... 

Benzylpenicillin (5.6), the first, and still the most used, member of the penicillin family, kills bacteria by combining covalently with a peptido-glycan transpeptidase , which normally brings about cross-linking, the final stage in murein biosynthesis (Izaki, Matsuhashi, and Strominger, 1968). Deprived of the opportunity to make new cell wall during a period of... 

An attractive hypothesis is the independent evolution in bacteria of their diffusible individualites and the currently recognized secondary metabolic pathways, in parallel with their surface components and their biosynthesis. An indicator for this would be the use of the same gene pool. The theory would include all substances that play a role in the build-up of glycan and other modified surface layers, lipids, murein, (glyco-) proteins (e.g., S-layers), polysaccharides, teichoic... 

Fig. 5. UDP-lV-acetyl-muraminic acid pentapeptide (1), an intermediate in the biosynthesis of murein in eubacteria...

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. 

Figure 11 Sequential murein biosynthetic pathway, the early steps of the bacterial cell wall biosynthesis.

Fig. 4. Comparison of the proposed schemes of the biosynthesis of murein and pseudomurein [40].

The participation of a nucleotide-activated disaccharide and UDP-activated peptide intermediates are unique features of pseudomurein biosynthesis. Usually, oligosaccharide precursors of bacterial cell-wall polymers are formed at the lipid stage [38,44] and amino acids carrying a nucleotide residue at the. /V -amino group have not been found in nature so far. The distinct differences between the two biosynthetic routes support the hypothesis that murein and pseudomurein represent independent inventions made after the domains bacteria and archaea had been separated from each other during evolution [40,46]. 

Mechanism of action In cell wall synthesis B. acts as an inhibitor of the biosynthesis of murein. 

Muramic acid N-acetyl-3-O-carboxyethyl-D-gJu-cosamine, or >-lactyl-lV-acetylglucosamine, m.p. 151 °C, [a]u 144°, an aminosugar derived from glucose, and an important constituent of mucopolysaccharide-peptide complexes of bacterial cell walls. For the biosynthesis of M.a., see Murein. 

Undecaprenol (bactoprenol) from Salmonella contains eleven isoprene units, and two irons and nine cis double bonds In the form of undecaprenyl phosphate, it acts as a carrier of carbohydrate residues in the biosynthesis of bacterial antigenic polysaccharides synthesis of Murein (see) also depends on undecaprenyl phosphate. In eukaryotes the Dolichol phosphates (see) function in the transfer of carbohydrate residues in the synthesis of glycoproteins and glycoli-pids. Probably the long lipid chains of these P serve to anchor them in membranes, while the phosphate group acts as a carrier by protruding into the cytoplasm. It is not known whether all P. function as carbohydrate carriers. The structural relationship between solanesol and plastoquinone-9 and ubiquinone-9, and the joint occurrence of these compounds suggest a precursor role for P. Biosynthesis of P. proceeds from mevalonic acid and the conformation of all double bonds is predetermined in early precursors. 

A strain of Streptomyces recognized as Str. olivaceus and isolated from a sample of soil obtained in Turkey was found to produce a family of peptidolipidic antibiotics along with prodigiosin and metacyclo-prodigiosin. These antibiotics interfered with the biosynthesis of murein and only the growth of actinomycetes was inhibited 123). 

The complete biosynthesis of xanthan, a water-soluble bacterial polysaccharide with a cellulose backbone (see Chapter 6, Fig. 6.18 for the structure), has been worked out by Dankert et al. [111-114]. The pentasaccharide repeating unit is attached to a polyprenol pyrophosphate lipid carrier [111], and the polymerization takes place by the addition of the repeating pentasaccharide from the polyprenol pyrophosphate pentasaccharide to the reducing end of the growing xanthan chain [114]. The mechanism of xanthan chain elongation is an insertion mechanism similar to those of murein. Salmonella 0-antigen, the dextrans, mutan, and alteman. 

The biosynthesis of murein. The first stage is biosynthesis of the characteristic monosaccharide. To begin with, AT-acetylglycosamine-i-phosphate and uridine triphosphate are united, in the cytoplasm, to give... 

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