transpeptidation

Transpeptidation is the enzymatic formation of peptide cross-links between peptide stems in bacterial peptidoglycan, the molecule that gives bacterial cell walls their rigidity. In many bacteria, peptidoglycan consists of linear glycan chains that are cross-linked by short peptide stems. Transpeptidases catalyze the cross-linking reaction, linking the fourth amino acid of one stem to the third amino acid of another, thereby forming 4-3 cross-links that stitch together adjacent glycan strands. Some bacteria also employ L,D-transpeptidases to generate alternative 3-3 cross-links, contributing to wall architecture in specific contexts.

The primary enzymes responsible are penicillin-binding proteins (PBPs) and related transpeptidases. Their activity is essential for cell-wall integrity, enabling growth and division while maintaining resistance to osmotic pressure. The transpeptidation reaction can be inhibited by β-lactam antibiotics, such as penicillin, which mimic the natural substrate and covalently acylate the enzyme’s active site. This blocks cross-link formation, weakening the cell wall and leading to cell lysis in susceptible bacteria.

In a broader sense, the term transpeptidation is sometimes used to describe other peptide-transfer reactions, but its most notable and well-characterized role is in peptidoglycan cross-linking. For protein synthesis, the related process of forming a peptide bond during elongation is typically described as peptidyl transfer rather than transpeptidation, though some older sources use the term in that context.