Skip to content

Addition by subtraction

By Omer Ad

Posttranslational modifications (PTMs) are responsible for some of the most exotic ribosomally synthesized peptide backbones in biology. Examples include manipulations to generate D-amino acids, thioether linkages, and even formation amino acids with sp2 hybridized α-carbons [1]. In a recent publication by Jörn Piel’s research group in Science, bacteria are capable of making another unusual PTM – α-keto-β-amino amide formation [2].

The manuscript describes the identification of a radical S-adenosylmethionine (rSAM) enzyme (PlpXY) capable of excising a tyramine equivalent from a peptide, resulting in the formation of an -keto–amino amide motif. Multiple LC-MS and NMR experiments were performed to characterize the modification and multiple peptide substrates were analyzed to determine the minimal recognition sequence required for conversion. Piel and co-workers were also able to modify a peptide containing an α-keto-β-amino amide with a fluorophore using the motif as a synthetic handle. Finally, the investigators show that PlpXY can be used generate genetically encoded α-keto-β-amides that may be of great benefit to the pharmaceutical industry.

  1. McIntosh JA, Donia MS, & Schmidt EW (2009) Ribosomal peptide natural products: bridging the ribosomal and nonribosomal worlds. Nat Prod Rep 26(4):537-559. doi:10.1039/B714132G
  2. Morinaka BI, et al. (2018) Natural noncanonical protein splicing yields products with diverse beta-amino acid residues. Science 359(6377):779-782. doi:10.1126/science.aao0157

Leave a Reply

Your email address will not be published. Required fields are marked *

This site uses Akismet to reduce spam. Learn how your comment data is processed.