New Paper by the Piel Lab
Introduction of D‐Amino Acids in Minimalistic Peptide Substrates by an S‐Adenosyl‐L‐Methionine Radical Epimerase
Anna L. Vagstad, Takefumi Kuranaga, Salomé Püntener, Vijaya R. Pattabiraman, Jeffrey W. Bode and Jörn Piel
Angew Chem Int Ed Engl. 2018 Dec 6; doi: 10.1002/anie.201809508.
Post-translational modifying enzymes from the S-adenosyl-L-methionine (AdoMet) radical superfamily garner attention due to their ability to accomplish challenging biochemical reactions. Among them, a family of AdoMet radical epimerases catalyze irreversible L- to D-amino acid transformations of diverse residues, including 18 sites in the complex sponge-derived polytheonamide toxins. These enzymes are from the proteusin family of ribosomally synthesized and post-translationally modified peptide natural products and act on precursor proteins with relatively large N-terminal leaders and highly variable core sequences. Here we report the in vitro activity of the model epimerase OspD and provide a closer look at its catalytic mechanism and substrate flexibility. The wild-type enzyme was capable of leader-independent epimerization toward not only the stand-alone core peptide, but also truncated and cyclic core variants. Introduction of D-amino acids can drastically alter the stability, structure, and activity of peptides; thus, epimerases offer opportunities in peptide bioengineering.
>> external page Publication