An expanded whole-cell model of E. coli links cellular physiology with mechanisms of growth rate control
Open accessAbstract
Growth and environmental responses are essential for living organisms to survive and adapt to constantly changing environments. In order to simulate new conditions and capture dynamic responses to environmental shifts in a developing whole-cell model of E. coli, we incorporated additional regulation, including dynamics of the global regulator guanosine tetraphosphate (ppGpp), along with dynamics of amino acid biosynthesis and translation. With the model, we show that under perturbed ppGpp conditions, small molecule feedback inhibition pathways, in addition to regulation of expression, play a role in ppGpp regulation of growth. We also found that simulations with dysregulated amino acid synthesis pathways provide average amino acid concentration predictions that are comparable to experimental results but on the single-cell level, concentrations unexpectedly show regular fluctuations. Additionally, during both an upshift and downshift in nutrient availability, the simulated cell responds similarly with a transient increase in the mRNA:rRNA ratio. This additional simulation functionality should support a variety of new applications and expansions of the E. coli Whole-Cell Modeling Project.
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Genome-wide models have been developed to represent other bacterial organisms, including Escherichia coli.
“Since this pioneering work, genome-wide models have been developed to represent other bacterial organisms, including Escherichia coli.8,20–22”
From How to build the virtual cell with artificial intelligence: Priorities and opportunities (2024) · cites this paper as [22]
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A distinct growth physiology enhances bacterial growth under rapid nutrient fluctuationsPreprint
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How to build the virtual cell with artificial intelligence: Priorities and opportunities
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- Authors
- Ahn-Horst, T. A., Mille, L. S., Sun, G., Morrison, J. H., & Covert, M. W.
- Affiliations
- Stanford University (US)
- Corresponding author
- Covert, Markus W.
- Venue
- npj Systems Biology and Applications
- Published
- 2022-08-19
- Volume
- 8
- Issue
- 1
- Pages
- 30-30
- ISSN
- 2056-7189 (ISSN-L)
- PMC
- PMC9391491
- OpenAlex
- W4292302479
- Cited by
- 53
- References
- 67
- Citations by year
- 2026: 17 · 2025: 13 · 2024: 12 · 2023: 10 · 2022: 1
- FWCI
- 2.94
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- npj Systems Biology and Applications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (GM140008)
- Kwanjeong Educational Foundation (Graduate Scholarship)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
- Keywords
- Escherichia coli, whole-cell model, growth rate control, ppGpp, amino acid biosynthesis, translational regulation, nutrient availability, global gene regulation
- MeSH terms
- Amino Acids, Escherichia coli, Guanosine Tetraphosphate, RNA, Messenger
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