Production of stable isotope enriched antimicrobial peptides in Escherichia coli: An application to the production of a N-15-enriched fragment of lactoferrin

A method is described for the production of recombinant isotopically enrich ed peptides in E. coli. Peptides are produced in high yield as fusion prote ins with ketosteroid isomerase which form insoluble inclusion bodies. This insoluble form allows easy purification, stabilizes the peptide against deg radation and prevents bactericidal activity of the peptide. Cyanogen bromid e cleavage released peptide which was conjugated with alkylamines to form l ipopeptide. An important advantage of this system is that it allows product ion of peptides that are toxic to bacteria, which we have demonstrated on a dodecapeptide based on residues 21-31 of human bactericidal protein lactof errin.