Biosynthesis of Bacterial Cell Walls

Mutasynthesis of New Antibiotics K. L. Rinehart, Pure Appl. Chem., 1977, 49,1361-1384. The Significance of D-Alanyl-D-Alanine Termini in the Biosynthesis of Bacterial Cell Walls and the Action of Penicillin, Vancomycin and Ristocetin H. R. Perkins and M. Nieto, Pure Appl. Chem., 1973, 35, 371-381. 

Biosynthesis of bacterial cell wall is remarkable in two respects (1) It entails the synthesis of a regularly cross-linked polymer and (2) Part of the synthesis takes place inside the cell and part outside the cell. The synthesis of cell wall is divided into three stages, which occur at different locations (1) synthesis of UDP-/V-acetylmuramyl-penta-peptide, (2) polymerization of IV-acetylglucosamine and N-acetylmuramyl-pentapeptide to form linear peptidoglycan strands, and (3) cross-linking of the peptidoglycan strands. 

J. L. Strominger. Structure and biosynthesis of bacterial cell walls in relation to the mechanism of action of antibiotics... 

Osborn, M. J. (1969). Structure and biosynthesis of bacterial cell wall. Annual Review of Biochemistry 38, 501. 

Beta-lactam antibiotics covalently bind to penicillin-binding proteins (PBPs) involved in the biosynthesis of bacterial cell walls. 

Isoprenoid Lipids.—Lipids which contain a mono- or pyro-phosphate link between a polyisoprenoid alcohol and a carbohydrate residue are important intermediates in the biosynthesis of bacterial cell walls. The monophosphate derivatives are probably involved in the addition of single carbohydrate residues to existing polysaccharide chains while the pyrophosphates are probably intermediates in the biosynthesis of the main chain. Ficaprenyl (13 = 10), famesyl (13 = 2), dolichyl (14 n = 18), and citro-nellyl (14 n = 1) a-D-mannopyranosyl phosphates have now been... 

C3H7O4P, Mr 138.06, crystals, mp. 94 °C, [aj -14° (HjO) soluble in water, antibiotic with a wide spectrum of activity produced by streptomycetes and pseudomonads. For the unusual biosynthesis, see Lit.. F. prevents the biosynthesis of bacterial cell walls by inhibiting pyruvate-uridine diphospho-A -acetylglucos-amine transferase (EC 2.5.1.7). The calcium and ammonium salts are used in therapy. F. achieves high urine levels after oral administration and single doses are used for urinary tract infections. 

Although their strained four-membered ring makes (3-lactam antibiotics susceptible to hydrolysis, this same elevated reactivity toward nucleophilic acyl substitution is responsible for their antibacterial properties. (3-Lactams act by deactivating an enzyme, transpeptidase, required for the biosynthesis of bacterial cell walls. The active site of... 

The role of undecaprenyl phosphate (C55, allylic) as a carrier of glycosyl units in the biosynthesis of bacterial cells walls is well established. Dolichyl phosphate plays a similar role in the synthesis of glycoproteins in animal systems. Evidence that prenyl lipids serve as glycosyl carriers in the biosynthesis of glycoproteins in plants is accumulating rapidly (Pont Lezica et al., 1976 Delmer al., 1978 Erickson et al., 1978). Several authors have recently reviewed the literature on the role of polyprenols as glycosyl carriers in plants (Hemming, 1978 Pont Lezica, 1979 Elbein, 1979). 

Teichoic Acids.—Recent reviews have referred to the occurrence and functions of membrane teichoic acids, the biosynthesis of bacterial cell walls and of teichoic acids in bacterial cell walls and membranes, and the surface carbohydrates of prokaryotic cells. ... 

Recent work on the structure and biosynthesis of bacterial cell walls has given some indication of the way in which the crosslinked polysaccharide components are formed. There are several justifications for including here a brief account of work in this field. Firstly, certain antibiotics (e.g. the penicillins, bacitracin A, novabiocin) are known specifically to inhibit bacterial cell-wall synthesis. If, as seems likely, the inhibition is of an enzyme-catalysed reaction, a knowledge of the particular substrates involved might lead to the design of more powerful bactericidal agents. Secondly, the particular type of cell... 

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