Resource constrained flux balance analysis predicts selective pressure on the global structure of metabolic networks
Open accessAbstract
BACKGROUND: A universal feature of metabolic networks is their hourglass or bow-tie structure on cellular level. This architecture reflects the conversion of multiple input nutrients into multiple biomass components via a small set of precursor metabolites. However, it is yet unclear to what extent this structural feature is the result of natural selection. RESULTS: We extend flux balance analysis to account for limited cellular resources. Using this model, optimal structure of metabolic networks can be calculated for different environmental conditions. We observe a significant structural reshaping of metabolic networks for a toy-network and E. coli core metabolism if we increase the share of invested resources for switching between different nutrient conditions. Here, hub nodes emerge and the optimal network structure becomes bow-tie-like as a consequence of limited cellular resource constraint. We confirm this theoretical finding by comparing the reconstructed metabolic networks of bacterial species with respect to their lifestyle. CONCLUSIONS: We show that bow-tie structure can give a system-level fitness advantage to organisms that live in highly competitive and fluctuating environments. Here, limitation of cellular resources can lead to an efficiency-flexibility tradeoff where it pays off for the organism to shorten catabolic pathways if they are frequently activated and deactivated. As a consequence, generalists that shuttle between diverse environmental conditions should have a more predominant bow-tie structure than specialists that visit just a few isomorphic habitats during their life cycle.
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Metabolic flexibility modeling can give insight into the evolution of metabolic pathways, demonstrating that genes encoding enzymes with high connectivity and high metabolic flux have a greater chance of conservation and are the most likely sites of metabolic regulation.
“Finally, metabolic flexibility modeling can give us insight into the evolution of metabolic pathways (291), demonstrating that genes encoding enzymes with high connectivity and high metabolic flux have a greater chance of conservation (12) and are the most likely sites of metabolic regulation (292).”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [291]
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- Authors
- Abedpour, N., & Kollmann, M.
- Affiliations
- Heinrich Heine University Düsseldorf (DE)
- Corresponding author
- Abedpour, Nima
- ORCID
- Abedpour, Nima
- Venue
- BMC Systems Biology
- Published
- 2015-11-23
- Volume
- 9
- Issue
- 1
- Pages
- 88-88
- ISSN
- 1752-0509 (ISSN-L)
- PMC
- PMC4657269
- OpenAlex
- W2178186954
- Cited by
- 7
- References
- 48
- Citations by year
- 2026: 1 · 2024: 1 · 2022: 1 · 2020: 1 · 2018: 2 · 2016: 1
- FWCI
- 0.43
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- BMC Systems Biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- European Molecular Biology Organization (ALTF 853-2011)
- Deutsche Forschungsgemeinschaft (EXC 1028, SPP 1395)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Keywords
- metabolic network structure, bow-tie structure, natural selection, network hubs, environmental variability
- MeSH terms
- Escherichia coli, Models, Biological, Selection, Genetic, Evolution, Molecular, Metabolic Networks and Pathways, Metabolic Flux Analysis
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