ArticleBMC systems biology2010
Antimalarial drug targets in Plasmodium falciparum predicted by stage-specific metabolic network analysis.
Article in BMC systems biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 115 citations in OpenAlex.
- Validated antimalarial drug target discovery using genome-scale metabolic modeling.Antimicrobial agents and chemotherapy · 2025Article
- Host cell CRISPR genomics and modelling reveal shared metabolic vulnerabilities in the intracellular development of Plasmodium falciparum and related hemoparasites.Nature communications · 2024Article
- Plant-Based Natural Bioactive Compounds 2,4-Ditert-Butylphenolas: A Potential Candidates Against SARS-Cov-2019.Energy nexus · 2022Article
- Linking nutrient sensing and gene expression in Plasmodium falciparum blood-stage parasites.Molecular microbiology · 2021Review
- Non-canonical metabolic pathways in the malaria parasite detected by isotope-tracing metabolomics.Molecular systems biology · 2021Article
- Metabolic modelling approaches for describing and engineering microbial communities.Computational and structural biotechnology journal · 2021Review
- Uncovering the Role of Metabolism in Oomycete-Host Interactions Using Genome-Scale Metabolic Models.Frontiers in microbiology · 2021Review
- Computational/in silico methods in drug target and lead prediction.Briefings in bioinformatics · 2020Review
- Genome-Scale Metabolic Modeling for Unraveling Molecular Mechanisms of High Threat Pathogens.Frontiers in cell and developmental biology · 2020Review
- Novel Approaches for Systems Biology of Metabolism-Oriented Pathogen-Human Interactions: A Mini-Review.Frontiers in cellular and infection microbiology · 2020Review
- Metabolic Model of themBio · 2019Article
- Computational Identification of Metabolic Pathways ofInternational journal of genomics · 2019Article
- Genome-wide characterization of Phytophthora infestans metabolism: a systems biology approach.Molecular plant pathology · 2018Article
- Biomedical applications of genome-scale metabolic network reconstructions of human pathogens.Current opinion in biotechnology · 2018Review
- Functional interrogation of Plasmodium genus metabolism identifies species- and stage-specific differences in nutrient essentiality and drug targeting.PLoS computational biology · 2018Article
- In Silico Knockout Screening ofBioMed research international · 2018Article
- Lessons from the genomes and transcriptomes of filarial nematodes.Molecular and biochemical parasitology · 2017Review
- Genomics of apicomplexan parasites.Critical reviews in biochemistry and molecular biology · 2017Review
- Antiplasmodial dihetarylthioethers target the coenzyme A synthesis pathway in Plasmodium falciparum erythrocytic stages.Malaria journal · 2017Article
- Bioenergetics-based modeling of Plasmodium falciparum metabolism reveals its essential genes, nutritional requirements, and thermodynamic bottlenecks.PLoS computational biology · 2017Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDespite enormous efforts to combat malaria the disease still afflicts up to half a billion people each year of which more than one million die. Currently no approved vaccine is available and resistances to antimalarials are widely spread. Hence, new antimalarial drugs are urgently needed.
resultsHere, we present a computational analysis of the metabolism of Plasmodium falciparum, the deadliest malaria pathogen. We assembled a compartmentalized metabolic model and predicted life cycle stage specific metabolism with the help of a flux balance approach that integrates gene expression data. Predicted metabolite exchanges between parasite and host were found to be in good accordance with experimental findings when the parasite's metabolic network was embedded into that of its host (erythrocyte). Knock-out simulations identified 307 indispensable metabolic reactions within the parasite. 35 out of 57 experimentally demonstrated essential enzymes were recovered and another 16 enzymes, if additionally the assumption was made that nutrient uptake from the host cell is limited and all reactions catalyzed by the inhibited enzyme are blocked. This predicted set of putative drug targets, shown to be enriched with true targets by a factor of at least 2.75, was further analyzed with respect to homology to human enzymes, functional similarity to therapeutic targets in other organisms and their predicted potency for prophylaxis and disease treatment.
conclusionsThe results suggest that the set of essential enzymes predicted by our flux balance approach represents a promising starting point for further drug development.
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