Engineering of a Peptide α-N-Methyltransferase to Methylate Non-Proteinogenic Amino Acids.

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. Thi

SUBMITTER: Song H 

PROVIDER: S-EPMC10947093 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature