RRC ID 53702
Author Adolfsen KJ, Brynildsen MP.
Title Futile cycling increases sensitivity toward oxidative stress in Escherichia coli.
Journal Metab. Eng.
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.
Volume 29
Pages 26-35
Published 2015-5
DOI 10.1016/j.ymben.2015.02.006
PII S1096-7176(15)00025-7
PMID 25732623
PMC PMC4430396
MeSH Adenosine Triphosphate / genetics Adenosine Triphosphate / metabolism DNA Repair / physiology Escherichia coli K12 / genetics Escherichia coli K12 / metabolism* Oxidative Stress / physiology* Reactive Oxygen Species / metabolism* Substrate Cycling / physiology*
IF 7.808
Prokaryotes E. coli