Unknown

Dataset Information

0

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


ABSTRACT: 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 (13)C- and (18)O-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.

SUBMITTER: Imker HJ 

PROVIDER: S-EPMC2800832 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Imker Heidi J HJ   Walsh Christopher T CT   Wuest William M WM  

Journal of the American Chemical Society 20091201 51


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 (13)C- and (18)O-labeling studies, we show that biosynthesis occurs via N-carboxylation to form an in  ...[more]

Similar Datasets

| S-EPMC2773804 | biostudies-literature
| S-EPMC5856630 | biostudies-literature
| S-EPMC4054136 | biostudies-literature
| S-EPMC3610659 | biostudies-literature
| S-EPMC4103027 | biostudies-literature
| S-EPMC5562517 | biostudies-literature
| S-EPMC3163001 | biostudies-literature
| S-EPMC6294602 | biostudies-other
| S-EPMC10769383 | biostudies-literature
| S-EPMC6783550 | biostudies-literature