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FEBS Lett. 2015 Jan 30;589(3):285-94. doi: 10.1016/j.febslet.2014.12.010. Epub 2014 Dec 20.

Construction of a genome-scale metabolic network of the plant pathogen Pectobacterium carotovorum provides new strategies for bactericide discovery.

Author information

1
State Key Laboratory of Agricultural Microbiology, College of Informatics, Huazhong Agricultural University, Wuhan 430070, PR China; Agricultural Bioinformatics Key Laboratory of Hubei Province, Center for Bioinformatics, Huazhong Agricultural University, Wuhan 430070, PR China.
2
Agricultural Bioinformatics Key Laboratory of Hubei Province, Center for Bioinformatics, Huazhong Agricultural University, Wuhan 430070, PR China.
3
Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Beijing 100081, PR China.
4
State Key Laboratory of Agricultural Microbiology, College of Informatics, Huazhong Agricultural University, Wuhan 430070, PR China; Agricultural Bioinformatics Key Laboratory of Hubei Province, Center for Bioinformatics, Huazhong Agricultural University, Wuhan 430070, PR China. Electronic address: llchen@mail.hzau.edu.cn.

Abstract

We reconstructed the first genome-scale metabolic network of the plant pathogen Pectobacterium carotovorum subsp. carotovorum PC1 based on its genomic sequence, annotation, and physiological data. Metabolic characteristics were analyzed using flux balance analysis (FBA), and the results were afterwards validated by phenotype microarray (PM) experiments. The reconstructed genome-scale metabolic model, iPC1209, contains 2235 reactions, 1113 metabolites and 1209 genes. We identified 19 potential bactericide targets through a comprehensive in silico gene-deletion study. Next, we performed virtual screening to identify candidate inhibitors for an important potential drug target, alkaline phosphatase, and experimentally verified that three lead compounds were able to inhibit both bacterial cell viability and the activity of alkaline phosphatase in vitro. This study illustrates a new strategy for the discovery of agricultural bactericides.

KEYWORDS:

Flux balance analysis; Metabolic network; Pectobacterium carotovorum subsp. carotovorum PC1; Phenotype microarray; Virtual screening

PMID:
25535697
DOI:
10.1016/j.febslet.2014.12.010
[Indexed for MEDLINE]
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