Diagnosis and mitigation of the systemic impact of genome reduction in <i>Escherichia coli</i> DGF-298

Genomic streamlining can be employed in model organisms to reduce complexity and enhance strain predictability. One of the most striking examples is the bacterial strain <i>Escherichia coli</i> DGF-298, notable for having over one-third of its genome deleted. However, such extensive genome modifications raise the question of how similar this simplified cell remains when compared with its parent, and what are the possible unintended consequences of this simplification. In this study, we used metabolic modeling along with iModulon-based transcriptomic analysis in different growth conditions to assess the impact of genome reduction on metabolism and gene regulation. We observed little impact of genomic reduction on the regulatory network of <i>E. coli</i> DGF-298 and identified a potential metabolic bottleneck leading to the constitutive activity of the SoxS iModulon. We then leveraged the model's predictions to successfully restore SoxS activity to the basal level.

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Publication Details

Journal
mBio
Published
2024-08-29
DOI
https://doi.org/10.1128/mbio.00873-24
Citations
2
Primary Topic
Microbial Metabolic Engineering and Bioproduction
Type
article
Field-Weighted Citation Impact
0.47

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article

Diagnosis and mitigation of the systemic impact of genome reduction in Escherichia coli DGF-298

Pierre‐Étienne Jacques, Colton J. Lloyd, Cameron Lamoureux, Dominick Matteau et al.
2 citations
mBio
Microbial Metabolic Engineering and Bioproduction
0.47
article

Diagnosis and mitigation of the systemic impact of genome reduction in Escherichia coli DGF-298

Pierre‐Étienne Jacques, Colton J. Lloyd, Cameron Lamoureux, Dominick Matteau, Antoine Champie, Jean‐Christophe Lachance, Bernhard Ø. Palsson, Adam M. Feist, Sébastien Rodrigue, Simon Jeanneau, Ananth Sastry, Frédéric Grenier
article en
2 citations

Abstract

Genomic streamlining can be employed in model organisms to reduce complexity and enhance strain predictability. One of the most striking examples is the bacterial strain <i>Escherichia coli</i> DGF-298, notable for having over one-third of its genome deleted. However, such extensive genome modifications raise the question of how similar this simplified cell remains when compared with its parent, and what are the possible unintended consequences of this simplification. In this study, we used metabolic modeling along with iModulon-based transcriptomic analysis in different growth conditions to assess the impact of genome reduction on metabolism and gene regulation. We observed little impact of genomic reduction on the regulatory network of <i>E. coli</i> DGF-298 and identified a potential metabolic bottleneck leading to the constitutive activity of the SoxS iModulon. We then leveraged the model's predictions to successfully restore SoxS activity to the basal level.

mBioVol. 15(10)
Université de Sherbrooke (CA), Novo Nordisk Foundation (DK), University of California San Diego (US), Technical University of Denmark (DK)
Université de Sherbrooke, Compute Canada, University of California, San Diego, Natural Sciences and Engineering Research Council of Canada, Fonds de recherche du Québec – Nature et technologies
Openalex Percentile: Top 35%
Microbial Metabolic Engineering and Bioproduction
0.47
DOIOpen Access PDFOpenAlex
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