@article{3828,
  keywords = {Bacterial Proteins, S-Adenosylmethionine, Amino Acid Sequence, Carbon-Sulfur Lyases, Multigene Family, Protein Processing, Post-Translational, Peptides, Models, Chemical, Streptococcus, Peptide Biosynthesis, Sulfides},
  author = {Alessio Caruso and Leah Bushin and Kenzie Clark and Ryan Martinie and Mohammad Seyedsayamdost},
  title = {Radical Approach to Enzymatic β-Thioether Bond Formation.},
  abstract = { <p>Ribosomally synthesized and post-translationally modified peptides (RiPPs) are an emerging class of natural products that harbor diverse chemical functionalities, usually introduced via the action of a small number of tailoring enzymes. We have been interested in RiPP biosynthetic gene clusters that encode unusual metalloenzymes, as these may install as yet unknown alterations. Using a new bioinformatic search strategy, we recently identified an array of unexplored RiPP gene clusters that are quorum sensing-regulated and contain one or more uncharacterized radical S-adenosylmethionine (RaS) metalloenzymes. Herein, we investigate the reaction of one of these RaS enzymes and find that it installs an intramolecular β-thioether bond onto its substrate peptide by connecting a Cys-thiol group to the β-carbon of an upstream Asn residue. The enzyme responsible, NxxcB, accepts several amino acids in place of Asn and introduces unnatural β-thioether linkages at unactivated positions. This new transformation adds to the growing list of Nature{\textquoteright}s peptide macrocyclization strategies and expands the already impressive catalytic repertoire of the RaS enzyme superfamily.</p> },
  year = {2019},
  journal = {J Am Chem Soc},
  volume = {141},
  pages = {990-997},
  month = {2019 Jan 16},
  issn = {1520-5126},
  doi = {10.1021/jacs.8b11060},
  language = {eng},
}