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

• Published in: FEBS letters 2015-01, Vol.589 (3), p.285-294
• Main Authors: Wang, Cheng, Deng, Zhi-Luo, Xie, Zhi-Ming, Chu, Xin-Yi, Chang, Ji-Wei, Kong, De-Xin, Li, Bao-Ju, Zhang, Hong-Yu, Chen, Ling-Ling
• Format: Article
• Language: English
• Subjects: Bacteria; Computer Simulation; Flux balance analysis; Genome, Bacterial; Metabolic network; Metabolic Networks and Pathways; Molecular Sequence Annotation; Pectobacterium; Pectobacterium carotovorum - genetics; Pectobacterium carotovorum - isolation & purification; Pectobacterium carotovorum - metabolism; Pectobacterium carotovorum subsp. carotovorum PC1; Phenotype; Phenotype microarray; Plant Diseases - genetics; Plant Diseases - microbiology; Plants - microbiology; Virtual screening
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2014.12.010

•With the completion of thousands of genome-sequencing projects, a growing number of genome-scale metabolic networks have been constructed.•In this study, 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), the results were afterwards validated by phenotype microarray (PM) experiments.•The reconstructed genome-scale metabolic model contains 2235 reactions, 1113 metabolites and 1209 genes.•We identified 19 potential bactericide targets through a comprehensive in silico gene-deletion study, which may provide a basis for developing new agricultural bactericides.•Then we performed a 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. 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.