Introduction of a Non-Natural Amino Acid into a Nonribosomal Peptide Antibiotic by Modification of Adenylation Domain Specificity

摘要

Nonribosomal peptides are a group of structurally diverse secondary metabolites, which include a number of important therapeutic agents and agrochemicals. The modular architecture of the nonribosomal peptide synthetases (NRPS), responsible for the assembly of these complex peptides, provides an attractive platform from which to engineer the biosynthesis of "non-natural" nonribosomal peptides. For example, NRPS module and domain exchanges have been used to produce cyclic lipopeptide variants of the clinically important antibiotic daptomycin.