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Research at St Andrews

Engineering of a peptide α-N-methyltransferase to methylate non-proteinogenic amino acids

Research output: Contribution to journalArticlepeer-review

DOI

Open Access Status

  • Embargoed (until 1/01/50)

Author(s)

James H. Naismith, Haigang Song, Antony J. Burton, Sally L. Shirran, Jūratė Fahrig-Kamarauskaitė, Hannelore Kaspar, Tom W. Muir, Markus Künzler

School/Research organisations

Abstract

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.
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Details

Original languageEnglish
JournalAngewandte Chemie International Edition
DOIs
Publication statusAccepted/In press - 14 Apr 2021

    Research areas

  • Cyclic peptide, RiPPs, α-N-methylation, Non-proteinogenic amino acids, Split intein

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