Abstract
Living cells can express different metabolic pathways that support growth. The criteria that determine which pathways are selected in which environment remain unclear. One recurrent selection is overflow metabolism: the simultaneous usage of an ATP-efficient and -inefficient pathway, shown for example in Escherichia coli, Saccharomyces cerevisiae and cancer cells. Many models, based on different assumptions, can reproduce this observation. Therefore, they provide no conclusive evidence which mechanism is causing overflow metabolism. We compare the mathematical structure of these models. Although ranging from flux balance analyses to self-fabricating metabolism and expression models, we can rewrite all models into one standard form. We conclude that all models predict overflow metabolism when two, model-specific, growth-limiting constraints are hit. This is consistent with recent theory. Thus, identifying these two constraints is essential for understanding overflow metabolism. We list all imposed constraints by these models, so that they can hopefully be tested in future experiments.
Original language | English |
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Pages (from-to) | 441-453 |
Number of pages | 13 |
Journal | Cellular and Molecular Life Sciences |
Volume | 77 |
Issue number | 3 |
Early online date | 22 Nov 2019 |
DOIs | |
Publication status | Published - 1 Feb 2020 |
Funding
DHdG and BT acknowledge NWO VICI grant 865.14.005, JL thanks EraCoBiotech grant YogurtDesign (NWO Grant 053.80.733) and RM acknowledges ITN SynCrop (Grant agreement no 764591) for financial support.
Funders | Funder number |
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NWO VICI | |
Horizon 2020 Framework Programme | 764591 |
Immune Tolerance Network | |
Nederlandse Organisatie voor Wetenschappelijk Onderzoek | 053.80.733, 865.14.005 |
Keywords
- Elementary flux modes
- Elementary growth modes
- Genome-scale modeling
- Growth rate maximization
- Metabolism and expression
- Overflow metabolism