期刊
FEBS LETTERS
卷 589, 期 3, 页码 285-294出版社
WILEY
DOI: 10.1016/j.febslet.2014.12.010
关键词
Metabolic network; Flux balance analysis; Phenotype microarray; Virtual screening; Pectobacterium carotovorum subsp.; carotovorum PC1
资金
- National Natural Science Foundation of China [31071659, 31271406]
- Program for New Century Excellent Talents in University [2013PY004]
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. (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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