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Expanding the computable reactome in Pseudomonas putida reveals metabolic cycles providing robustness

Juan Nogales, Steinn Gudmundsson, Estrella Duque, Juan Luis Ramos, Bernhard O. Palsson
doi: https://doi.org/10.1101/139121
Juan Nogales
aDepartment of Bioengineering, University of California, San Diego, La Jolla, CA, USA
bDepartment of Environmental Biology, Centro de Investigaciones Biológicas-CSIC, Madrid, Spain
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  • For correspondence: jnogales@cib.csic.es
Steinn Gudmundsson
cCenter for Systems Biology, University of Iceland, Iceland
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Estrella Duque
dBiotechnology Research Area, Abengoa Research, Sevilla, Spain
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Juan Luis Ramos
dBiotechnology Research Area, Abengoa Research, Sevilla, Spain
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Bernhard O. Palsson
aDepartment of Bioengineering, University of California, San Diego, La Jolla, CA, USA
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Abstract

Genome-scale network reconstructions are organism-specific representations of metabolism and powerful tools for analyzing systemic metabolic properties. The use of reconstructions is limited by the lack of coverage of the metabolic reactome. We present an exhaustive and validated reconstruction of the biotechnologically relevant bacterium Pseudomonas putida KT2440, greatly expanding its computable metabolic states. The reconstruction, iJN1411, represents a significant expansion over other reconstructed bacterial metabolic networks. Computations based on the reconstruction exhibit high accuracy in predicting nutrient sources, growth rates, carbon flux distributions, and gene essentiality, thus providing a deep understanding of Pseudomonas metabolism. iJN1411 was used for: i) the assessment of the metabolic capabilities of P. putida as a species through multi-strain modeling, ii) deciphering the molecular mechanisms underlying metabolic robustness, and iii) identification of metabolic “capacitors” based on ATP-fueled metabolic cycles. This study represents the most complete and comprehensive bacterial metabolic reconstruction built to date, while providing computational and experimental evidence about how bacteria increase metabolic robustness, paving the way for engineering more robust biocatalysts and searching for drug targets in robust pathogens.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted May 19, 2017.
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Expanding the computable reactome in Pseudomonas putida reveals metabolic cycles providing robustness
Juan Nogales, Steinn Gudmundsson, Estrella Duque, Juan Luis Ramos, Bernhard O. Palsson
bioRxiv 139121; doi: https://doi.org/10.1101/139121
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Expanding the computable reactome in Pseudomonas putida reveals metabolic cycles providing robustness
Juan Nogales, Steinn Gudmundsson, Estrella Duque, Juan Luis Ramos, Bernhard O. Palsson
bioRxiv 139121; doi: https://doi.org/10.1101/139121

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