Biosynthesis pathway, bacterial cell

The pathway from simple molecules to the peptidoglycan of the bacterial cell wall is lengthy and complex. Many of the details are well known but need not concern us here. Suffice it to say that long carbohydrate chains are synthesized, subsequently decorated with shorter amino acid chains, and these are finally cross-linked to provide a strong strnctnre. It is this final cross-linking step that is inhibited by the p-lactam antibiotics. The consequence is that cell wall biosynthesis cannot be completed and cell death ensnes. Again, the mammalian host carries out no similar reactions so that similar consequences do not ensne for the host orgaiusm. 

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

The ability to isolate the many auxotrophic (nutritionally dependent) strains of Escherichia coli and Aerobacter aerogenes, with which Davis elucidated several pathways in biosynthesis, depended on his use of the observation that only under conditions which allow growth to take place does penicillin kill bacterial cells. Essentially the same method was developed, simultaneously and independently, by Lederberg and Zinder. ... 

This can be achieved in a variety of ways. For instance, it is possible to inhibit an essential pathway in the pathogen that does not exist in the host. o-Cycloserine (1) (Fig. 17.1), for example, inhibits alanine race-mase, an enzyme involved in bacterial cell wall biosynthesis and not found in humans (8, 9). D-Cycloserine is active against a broad spectrum of both gram-positive and gramnegative bacteria (10), but plays its major role in the treatment of tuberculosis (11). Conversely, even if both host and pathogen contain the same enzymes, it may be possi-... 

Fig. 12.2 Pathway for the biosynthesis of peptidoglycan in bacterial cells showing the sites of action of cycloserine, glycopeptide and p-lactam antibiotics.

Figure 1. The bacterial cell wall biosynthesis pathway.

Bacteria synthesize lysine through one of three different pathways that are not present in mammals. " An intermediate in these pathways, wj ro-diaminopimelic acid (mDAP), is also an essential component of the bacterial cell wall. " " Consequently, the enzymes in these pathways are targets for the development of antibiotics for treatment of Gram-negative and Gram-positive bacterial infections. The enzyme DapE catalyzes the hydrolysis of N-succinyl-L,L-diaminopimelic acid to form L,L-diaminopimelic acid and succinate in the succinylase pathway of lysine biosynthesis (Figure 6(i)). 

Microorganisms are proficient in synthesizing a large number of polysaccharides. The pathways for their biosynthesis are similar to the procedures that take place for the formation bacterial cell wall. It is anticipated that there are well over 100 enzymatic reactions, directly or indirectly involved in the synfliesis of polysaccharides. Initially with glucose, suitable sugars (by transforming glucose to others) are included in the formation of polysaccharides. 

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