Multi-scale model of the proteomic and metabolic consequences of reactive oxygen species

Yang, L.; Mih, N.; Yurkovich, J. T.; Park, J. H.; Seo, S.; Kim, D.; Monk, J. M.; Lloyd, C. J.; Tan, J.; Gao, Y.; Broddrick, J. T.; Chen, K.; Heckmann, D.; Feist, A. M.; Palsson, B. O.

doi:10.1101/227892

bioRxiv · 10.1101/227892

Multi-scale model of the proteomic and metabolic consequences of reactive oxygen species

Yang, L.·Mih, N.·Yurkovich, J. T.·Park, J. H.·Seo, S.·Kim, D.·Monk, J. M.·Lloyd, C. J.·Tan, J.·Gao, Y.·Broddrick, J. T.·Chen, K.·Heckmann, D.·Feist, A. M.·Palsson, B. O.

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Abstract

Catalysis using iron-sulfur clusters and transition metals can be traced back to the last universal common ancestor. The damage to metalloproteins caused by reactive oxygen species (ROS) can completely inhibit cell growth when unmanaged and thus elicits an essential stress response that is universal and fundamental in biology. We develop a computable multi-scale description of the ROS stress response in Escherichia coli. We show that this quantitative framework allows for the understanding and prediction of ROS stress responses at three levels: 1) pathways: amino acid auxotrophies, 2) networks: the systemic response to ROS stress, and 3) genetic basis: adaptation to ROS stress during laboratory evolution. These results show that we can now develop fundamental and quantitative genotype-phenotype relationships for stress responses on a genome-wide basis.

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Yang, L., Mih, N., Yurkovich, J. T., Park, J. H., Seo, S., Kim, D., Monk, J. M., Lloyd, C. J., Tan, J., Gao, Y., Broddrick, J. T., Chen, K., Heckmann, D., Feist, A. M., Palsson, B. O.. 2017-12-02. Multi-scale model of the proteomic and metabolic consequences of reactive oxygen species. https://doi.org/10.1101/227892

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