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Futile cycling increases sensitivity toward oxidative stress in Escherichia coli

Author(s): Adolfsen, Kristin J; Brynildsen, Mark P

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Abstract: Reactive oxygen species (ROS) are toxic molecules utilized by the immune system to combat invading pathogens. Recent evidence suggests that inefficiencies in ATP production or usage can lead to increased endogenous ROS production and sensitivity to oxidative stress in bacteria. With this as inspiration, and knowledge that ATP is required for a number of DNA repair mechanisms, we hypothesized that futile cycling would be an effective way to increase sensitivity to oxidative stress. We developed a mixed integer linear optimization framework to identify experimentally-tractable futile cycles, and confirmed metabolic modeling predictions that futile cycling depresses growth rate, and increases both O2 consumption and ROS production per biomass generated. Further, intracellular ATP was decreased and sensitivity to oxidative stress increased in all actively cycling strains compared to their catalytically inactive controls. This research establishes a fundamental connection between ATP metabolism, endogenous ROS production, and tolerance toward oxidative stress in bacteria.
Publication Date: May-2015
Electronic Publication Date: 15-Feb-2015
Citation: Adolfsen, Kristin J, Brynildsen, Mark P. (2015). Futile cycling increases sensitivity toward oxidative stress in Escherichia coli. METABOLIC ENGINEERING, 29 (26 - 35. doi:10.1016/j.ymben.2015.02.006
DOI: doi:10.1016/j.ymben.2015.02.006
ISSN: 1096-7176
EISSN: 1096-7184
Pages: 26 - 35
Type of Material: Journal Article
Journal/Proceeding Title: METABOLIC ENGINEERING
Version: Author's manuscript

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