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Title 

Cephalochromin, a FabI-directed antibacterial of microbial origin

Authors 

C J ZhengMi Jin SohnSangku LeeYoung-Soo HongJ H KwakWon Gon Kim

Publisher 

Elsevier

Issue Date 

2007

Citation 

Biochemical and Biophysical Research Communications, vol. 362, no. 4, pp. 1107-1112

Keywords 

antibacterialcephalochrominenoyl-ACP reductasefabIfatty acid synthesisnaphtho-γ-pyroneantibiotic agentantiinfective agentbacterial protein

Abstract 

Microorganisms produce many kinds of antibiotics which function in an antagonistic capacity in nature where they have much competition. Bacterial enoyl-acyl carrier protein (ACP) reductase (FabI) has been demonstrated to be an antibacterial target. However, no FabI-directed antibiotic of microbial origin has been reported so far. In this study, we found that cephalochromin with a naphtho-γ-pyrone skeleton, a fungal secondary metabolite, inhibited FabI of Staphylococcus aureus and Escherichia coli with IC50 of 1.9 and 1.8 μM, respectively. The methylether derivatives of cephalochromin, however, did not inhibit FabI. The FabI-inhibitory activities of cephalochromin and its derivatives well correlated with antibacterial activity as well as the inhibition of cellular fatty acid biosynthesis. Furthermore, FabI-overexpressing S. aureus exhibited reduced susceptibility to cephalochromin compared to the wild-type strain, demonstrating that the mode of antibacterial action of cephalochromin is via the inhibition of FabI. These results indicate that cephalochromin is the first FabI-directed antibacterial of microbial origin and may have the potential for further antibacterial development.

ISSN 

0006-291X

Link 

http://dx.doi.org/10.1016/j.bbrc.2007.08.144

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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