Tailoring enzymes that modify nonribosomal peptides during and after chainelongation on NRPS assembly lines

Nonribosomal peptide synthetases are large enzyme complexes that synthesize a variety of peptide natural products through a thiotemplated mechanism. A ssembly of the peptides proceeds through amino acid loading, amide-bond for mation and chain translocation, and finally thioester lysis to release the product. The final products are often heavily modified, however, through me thylation, epimerization, hydroxylation, heterocyclization, oxidative cross -linking and attachment of sugars. These activities are the province of spe cialized enzymes (either embedded in the multidomain nonribosomal peptide s ynthetase structure or standalone).