Autocatalytic backbone N-methylation in a family of ribosomal peptide natural products

June 5th, 2017 by Niels S van der Velden

Nature Chemical Biology 13, 833 (2017). doi:10.1038/nchembio.2393

Authors: Niels S van der Velden, Noemi Kälin, Maximilian J Helf, Jörn Piel, Michael F Freeman & Markus Künzler

Peptide backbone N-methylation, as seen in cyclosporin A, has been considered to be exclusive to nonribosomal peptides. We have identified the first post-translationally modified peptide or protein harboring internal α-N-methylations through discovery of the genetic locus for the omphalotins, cyclic N-methylated peptides produced by the fungus Omphalotus olearius. We show that iterative autocatalytic activity of an N-methyltransferase fused to its peptide substrate is the signature of a new family of ribosomally encoded metabolites.

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