Peptidoglycan Synthesis

Peptidoglycan, a key bacterial cell wall component, is made of alternating N-acetylglucosamine, or NAG, and N-acetylmuramic acid or NAM units joined by β-1,4 glycosidic bonds.

Peptidoglycan synthesis involves three phases. In the cytoplasm, uridine diphosphate (UDP) molecules are covalently attached to NAG.

UDP-NAG gets enzymatically converted to UDP-NAM. Then, a pentapeptide chain is added to UDP-NAM to form a UDP-NAM-pentapeptide.

In the membrane-associated phase, the NAM-pentapeptide is linked to bactoprenol phosphate, forming Lipid I on the cytoplasmic side of the plasma membrane.

The addition of a NAG unit to Lipid I forms Lipid II, which is translocated across the membrane to the periplasm by a flippase.

In the periplasmic phase, glycosyltransferases form glycosidic bonds to add the NAG-NAM-pentapeptide to the growing peptidoglycan chain attached to bactoprenol.

In the final step, the transpeptidase enzyme forms peptide cross-links between glycan chains, releases the chain from bactoprenol, and completes synthesis by linking stem peptides.