Title | Engineering of a Peptide α-N-Methyltransferase to Methylate Non-Proteinogenic Amino Acids. |
Publication Type | Journal Article |
Year of Publication | 2021 |
Authors | Song, H, Burton, AJ, Shirran, SL, Fahrig-Kamarauskaitė, J, Kaspar, H, Muir, TW, Künzler, M, Naismith, JH |
Journal | Angew Chem Int Ed Engl |
Volume | 60 |
Issue | 26 |
Pagination | 14319-14323 |
Date Published | 2021 Jun 21 |
ISSN | 1521-3773 |
Keywords | Amides, Amino Acids, Methylation, Methyltransferases, Peptides, Protein Conformation, Protein Engineering |
Abstract | <p>Introduction of α-N-methylated non-proteinogenic amino acids into peptides can improve their biological activities, membrane permeability and proteolytic stability. This is commonly achieved, in nature and in the lab, by assembling pre-methylated amino acids. The more appealing route of methylating amide bonds is challenging. Biology has evolved an α-N-automethylating enzyme, OphMA, which acts on the amide bonds of peptides fused to its C-terminus. Due to the ribosomal biosynthesis of its substrate, the activity of this enzyme towards peptides with non-proteinogenic amino acids has not been addressed. An engineered OphMA, intein-mediated protein ligation and solid-phase peptide synthesis have allowed us to demonstrate the methylation of amide bonds in the context of non-natural amides. This approach may have application in the biotechnological production of therapeutic peptides.</p> |
DOI | 10.1002/anie.202100818 |
Alternate Journal | Angew Chem Int Ed Engl |
PubMed ID | 33856715 |
PubMed Central ID | PMC8251615 |
Grant List | BB/R018189/1 / BB_ / Biotechnology and Biological Sciences Research Council / United Kingdom |