Blurring the lines between ribosomal and nonribosomal peptide scaffolds

Two of the canons of protein science have been (1) that there are 20-22 amino acids that are proteinogenic and (2), with the exception of achiral glycine, that the other residues are L-amino acids. By contrast, the presence of nonproteinogenic amino acid residues and D-enantiomers has been regarded as hallmarks of nonribosomal peptides. The recent discoveries that bottromycins and polytheonamides, containing β-methyl and D-amino acid residues, are of ribosomal origin blur the distinctions between peptide structures derivable by ribosomal and nonribosomal assembly lines and reveal new chemistry for posttranslational maturation of proteins.