Actinonin, a naturally occurring antibacterial agent, is a potent deformylase inhibitor

被引：260

作者：

Chen, DZ ^{[1
]}

Patel, DV ^{[1
]}

Hackbarth, CJ ^{[1
]}

Wang, W ^{[1
]}

Dreyer, G ^{[1
]}

Young, DC ^{[1
]}

Margolis, PS ^{[1
]}

Wu, C ^{[1
]}

Ni, ZJ ^{[1
]}

Trias, J ^{[1
]}

White, RJ ^{[1
]}

Yuan, ZY ^{[1
]}

机构：

[1] Versicor Inc, Fremont, CA 94555 USA

来源：

BIOCHEMISTRY | 2000年 / 39卷 / 06期

关键词：

D O I：

10.1021/bi992245y

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Peptide deformylase (PDF) is essential in prokaryotes and absent in mammalian cells, thus making it an attractive target for the discovery of novel antibiotics. We have identified actinonin, a naturally occurring antibacterial agent, as a potent PDF inhibitor. The dissociation constant for this compound was 0.3 x 10(-9) M against Ni-PDF from Escherichia coli; the PDF from Staphylococcus aureus gave a similar value. Microbiological evaluation revealed that actinonin is a bacteriostatic agent with activity against Gram-positive and fastidious Gram-negative microorganisms. The PDF gene, def, was placed under control of P-BAD in E. coli tolC, permitting regulation of PDF expression levels in the cell by varying the external arabinose concentration. The susceptibility of this strain to actinonin increases with decreased levels of PDF expression, indicating that actinonin inhibits bacterial growth by targeting this enzyme. Actinonin provides an excellent starting point from which to derive a more potent PDF inhibitor that has a broader spectrum of antibacterial activity.

引用

页码：1256 / 1262

页数：7

共 42 条

[1] ON RELEASE OF FORMYL GROUP FROM NASCENT PROTEIN [J].