Formation of the glycan chains in the synthesis of bacterial peptidoglycan

The main structural features of bacterial peptidoglycan are linear glycan c hains interlinked by short peptides. The glycan chains are composed of alte rnating units of N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (Mur NAc), all linkages between sugars being beta ,1-->4. On the outside of the cytoplasmic membrane, two types of activities are involved in the polymeriz ation of the peptidoglycan monomer unit: glycosyltransferases that catalyze the formation of the linear glycan chains and transpeptidases that catalyz e the formation of the peptide cross-bridges. Contrary to the transpeptidat ion step, for which there is an abundant literature that has been regularly reviewed, the transglycosylation step has been studied to a far lesser ext ent. The aim of the present review is to summarize and evaluate the molecul ar and cellullar data concerning the formation of the glycan chains in the synthesis of peptidoglycan. Early work concerned the use of various in vivo and in vitro systems for the study of the polymerization steps, the attach ment of newly made material to preexisting peptidoglycan, and the mechanism of action of antibiotics. The synthesis of the glycan chains is catalyzed by the N-terminal glycosyltransferase module of class A high-molecular-mass penicillin-binding proteins and by nonpenicillin-binding monofunctional gl ycosyltransferases. The multiplicity of these activities in a given organis m presumably reflects a variety of in vivo functions. The topological local ization of the incorporation of nascent peptidoglycan into the cell wall ha s revealed that bacteria have at least two peptidoglycan-synthesizing syste ms: one for septation, the other one for elongation or cell wall thickening . Owing to its location on the outside of the cytoplasmic membrane and its specificity, the transglycosylation step is an interesting target for antib acterials. Glycopeptides and moenomycins are the best studied antibiotics k nown to interfere with this step. Their mode of action and structure-activi ty relationships have been extensively studied. Attempts to synthesize othe r specific transglycosylation inhibitors have recently been made.