Article

Reconstruction and flux-balance analysis of the Plasmodium falciparum metabolic network

Center for Computational Biology and Bioinformatics, Columbia University, New York City, NY 10032, USA.
Molecular Systems Biology (Impact Factor: 10.87). 09/2010; 6(1):408. DOI: 10.1038/msb.2010.60
Source: PubMed

ABSTRACT

Genome-scale metabolic reconstructions can serve as important tools for hypothesis generation and high-throughput data integration. Here, we present a metabolic network reconstruction and flux-balance analysis (FBA) of Plasmodium falciparum, the primary agent of malaria. The compartmentalized metabolic network accounts for 1001 reactions and 616 metabolites. Enzyme-gene associations were established for 366 genes and 75% of all enzymatic reactions. Compared with other microbes, the P. falciparum metabolic network contains a relatively high number of essential genes, suggesting little redundancy of the parasite metabolism. The model was able to reproduce phenotypes of experimental gene knockout and drug inhibition assays with up to 90% accuracy. Moreover, using constraints based on gene-expression data, the model was able to predict the direction of concentration changes for external metabolites with 70% accuracy. Using FBA of the reconstructed network, we identified 40 enzymatic drug targets (i.e. in silico essential genes), with no or very low sequence identity to human proteins. To demonstrate that the model can be used to make clinically relevant predictions, we experimentally tested one of the identified drug targets, nicotinate mononucleotide adenylyltransferase, using a recently discovered small-molecule inhibitor. © 2010 EMBO and Macmillan Publishers Limited All rights reserved.

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Available from: Germán Plata, Aug 05, 2014
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    • "After the manual correction, iJN746 was able to produce a non-zero biomass flux. Another five models, iNJ661m [61], iNJ661v [61], iSR432 [62], iTZ479 [13], and iTH366 [63] , initially failed to generate a non-zero biomass flux under FBA when loaded with the sbmlstrict option. A close examination of these non-viable models revealed additional inconsistencies in SBML syntax, where an attribute named " boundaryCondition " was missing. "
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