Peptidoglycan is a complex polymer consisting, for the purposes of description, of three parts: a backbone, composed of alternating N-acetylglucosamine and N-acetylmuramic acid connected by β1→4 linkages; a set of identical tetrapeptide side chains attached to N-acetylmuramic acid; and a set of identical peptide cross-bridges (Figure 1). The backbone is the same in all bacterial species; the tetrapeptide side chains and the peptide cross-bridges vary from species to species. In many Gram-negative cell walls, the cross-bridge consists of a direct peptide linkage between the diaminopimelic acid (DAP) amino group of one side chain and the carboxyl group of the terminal d-alanine of a second side chain.
Fig1. Components and structure of peptidoglycan. A: Chemical structure of N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM); the ring structures of the two molecules are glucose. Glycan chains are composed of alternating subunits of NAG and NAM joined by covalent bonds. Adjacent glycan chains are cross-linked via their tetrapeptide chains to create peptidoglycan. B: Interconnected glycan chains form a very large three-dimensional molecule of peptidoglycan. The β1→4 linkages in the backbone are cleaved by lysozyme. (Reproduced with permission from Nester EW, Anderson DG, Roberts CE, et al: Microbiology: A Human Perspective, 6th ed. McGraw-Hill, 2009. © McGraw-Hill Education.)
The tetrapeptide side chains of all species, however, have certain notable features in common. Most have l-alanine at position 1 (attached to N-acetylmuramic acid), d-glutamate or substituted d-glutamate at position 2, and d-alanine at position 4. Position 3 is the most variable one: Most Gram-negative bacteria have diaminopimelic acid at this position, to which is linked the lipoprotein cell wall component discussed as follows. Gram-positive bacteria usually have l-lysine at position 3; however, some may have diaminopimelic acid or another amino acid at this position.
Diaminopimelic acid is a unique element of bacterial cell walls. It is never found in the cell walls of Archaea or eukaryotes. Diaminopimelic acid is the immediate precursor of lysine in the bacterial biosynthesis of that amino acid. Bacterial mutants that are blocked before diaminopimelic acid in the biosynthetic pathway grow normally when provided with diaminopimelic acid in the medium; when given l-lysine alone, however, they lyse, because they continue to grow but are specifically unable to make new cell wall peptidoglycan.
The fact that all peptidoglycan chains are cross-linked means that each peptidoglycan layer is a single giant molecule. In Gram-positive bacteria, there are as many as 40 sheets of peptidoglycan, comprising up to 50% of the cell wall material; in Gram-negative bacteria, there appears to be only one or two sheets, comprising 5–10% of the wall material. Bacteria owe their shapes, which are characteristic of particular species, to their cell wall structure.
