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Title 

Integrative genome-scale metabolic analysis of Vibrio vulnificus for drug targeting and discovery

Authors 

H U KimS Y KimHaeyoung JeongT Y KimJ J KimH E ChoyK Y YiJ H RheeS Y Lee

Publisher 

Nature / European Molecular Biology Organization

Issue Date 

2011

Citation 

Molecular Systems Biology, vol. 7, no. 0, pp. 460-460

Keywords 

drug discoverydrug targetinggenome analysismetabolic networkVibrio vulnificus

Abstract 

Although the genomes of many microbial pathogens have been studied to help identify effective drug targets and novel drugs, such efforts have not yet reached full fruition. In this study, we report a systems biological approach that efficiently utilizes genomic information for drug targeting and discovery, and apply this approach to the opportunistic pathogen Vibrio vulnificus CMCP6. First, we partially re-sequenced and fully re-annotated the V. vulnificus CMCP6 genome, and accordingly reconstructed its genome-scale metabolic network, VvuMBEL943. The validated network model was employed to systematically predict drug targets using the concept of metabolite essentiality, along with additional filtering criteria. Target genes encoding enzymes that interact with the five essential metabolites finally selected were experimentally validated. These five essential metabolites are critical to the survival of the cell, and hence were used to guide the cost-effective selection of chemical analogs, which were then screened for antimicrobial activity in a whole-cell assay. This approach is expected to help fill the existing gap between genomics and drug discovery.

ISSN 

1744-4292

Link 

http://dx.doi.org/10.1038/msb.2010.115

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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