SylC catalyzes ureido-bond formation during biosynthesis of the proteasome inhibitor syringolin A

Heidi J. Imker, Christopher T. Walsh, William M. Wuest

Research output: Contribution to journalArticle

Abstract

(Chemical Equation Presented) Syringolins are a class of cyclic tripeptide natural products that are potent and irreversible inhibitors of the eukaryotic proteasome. In addition to being hybrid NRPS/PKS molecules, they also feature an unusual ureido-linkage (red) between two amino acid monomers. Here we report the first in vitro characterization of enzymatic ureido-linkage formation which is catalyzed by an NRPS, SylC. Using 13C- and 18O-labeling studies, we show that biosynthesis occurs via N-carboxylation to form an initial N-carboxy-aminoacyl-S-Ppant enzyme intermediate which undergoes intramolecular cyclization followed by condensation with a second amino acid to form the ureido-containing dipeptide product.

Original languageEnglish (US)
Pages (from-to)18263-18265
Number of pages3
JournalJournal of the American Chemical Society
Volume131
Issue number51
DOIs
StatePublished - Dec 30 2009
Externally publishedYes

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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