Engineering of a Peptide ??N?Methyltransferase to Methylate Non?Proteinogenic Amino Acids

Introduction of ?-N-methylated non-proteinogenic amino acids into peptides can improve their biological activities, membrane permeability and proteolytic stability. This is commonly achieved, in nature the lab, by assembling pre-methylated acids. The more appealing route methylating amide bonds challenging. Biology has evolved an ?-N-automethylating enzyme, OphMA, which acts on fused to its C-terminus. Due ribosomal biosynthesis substrate, activity this enzyme towards with not been addressed. An engineered intein-mediated protein ligation solid-phase peptide synthesis have allowed us demonstrate methylation context non-natural amides. approach may application biotechnological production therapeutic peptides.