SylC Catalyzes Ureido-Bond Formation During Biosynthesis of the Proteasome Inhibitor Syringolin A

被引：41

作者：

Imker, Heidi J. ^{[1
]}

Walsh, Christopher T. ^{[1
]}

Wuest, William M. ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2009年 / 131卷 / 51期

关键词：

PV.-SYRINGAE; CRYSTAL-STRUCTURE; SUPERFAMILY; BORTEZOMIB; ELICITOR;

D O I：

10.1021/ja909170u

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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 C-13- and O-18-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.

引用

页码：18263 / +

页数：4

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