Automated generation of bacterial resource allocation models

Resource Balance Analysis (RBA) is a computational method based on resource allocation, which performs accurate quantitative predictions of whole-cell states (i.e. growth rate, metabolic fluxes, abundances of molecular machines including enzymes) across growth conditions. We present an integrated wo...

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Bibliographic Details
Published in:Metabolic engineering 2019-09, Vol.55, p.12-22
Main Authors: Bulović, Ana, Fischer, Stephan, Dinh, Marc, Golib, Felipe, Liebermeister, Wolfram, Poirier, Christian, Tournier, Laurent, Klipp, Edda, Fromion, Vincent, Goelzer, Anne
Format: Article
Language:English
Subjects:
Bacillus subtilis - genetics
Bacillus subtilis - metabolism
Computer Science
Escherichia coli - genetics
Escherichia coli - metabolism
Life Sciences
Mathematics
Models, Biological
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Summary:Resource Balance Analysis (RBA) is a computational method based on resource allocation, which performs accurate quantitative predictions of whole-cell states (i.e. growth rate, metabolic fluxes, abundances of molecular machines including enzymes) across growth conditions. We present an integrated workflow of RBA together with the Python package RBApy. RBApy builds bacterial RBA models from annotated genome-scale metabolic models by adding descriptions of cellular processes relevant for growth and maintenance. The package includes functions for model simulation and calibration and for interfacing to Escher maps and Proteomaps for visualization. We demonstrate that RBApy faithfully reproduces results obtained by a hand-curated and experimentally validated RBA model for Bacillus subtilis. We also present a calibrated RBA model of Escherichia coli generated from scratch, which obtained excellent fits to measured flux values and enzyme abundances. RBApy makes whole-cell modelling accessible for a wide range of bacterial wild-type and engineered strains, as illustrated with a CO2-fixing Escherichia coli strain. RBApy is available at /https://github.com/SysBioInra/RBApy, under the licence GNU GPL version 3, and runs on Linux, Mac and Windows distributions. •The RBApy framework generates calibrated Resource Balance Analysis (RBA) models.•RBA models contain the whole metabolic network and the macromolecular processes.•Model calibration is performed using datasets available in the literature.•Calibrated models of WT and CO2-fixing E. coli strains are generated from scratch.•Whole-cell modelling is accessible for wild-type and engineered strains.
ISSN:1096-7176
1096-7184
DOI:10.1016/j.ymben.2019.06.001