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Title: Cellular responses to reactive oxygen species are predicted from molecular mechanisms

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 prevent cell growth and survival when unmanaged, thus eliciting an essential stress response that is universal and fundamental in biology. Here we develop a computable multiscale description of the ROS stress response in Escherichia coli, called OxidizeME. We use OxidizeME to explain four key responses to oxidative stress: 1) ROS-induced auxotrophy for branched-chain, aromatic, and sulfurous amino acids; 2) nutrient-dependent sensitivity of growth rate to ROS; 3) ROS-specific differential gene expression separate from global growth-associated differential expression; and 4) coordinated expression of iron–sulfur cluster (ISC) and sulfur assimilation (SUF) systems for iron–sulfur cluster biosynthesis. These results show that we can now develop fundamental and quantitative genotype–phenotype relationships for stress responses on a genome-wide basis.

Authors:
Publication Date:
Research Org.:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States). National Energy Research Scientific Computing Center (NERSC); Univ. of California, Oakland, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1577615
Grant/Contract Number:  
[AC02-05CH11231]
Resource Type:
Accepted Manuscript
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
[ Journal Volume: 116; Journal Issue: 28]; Journal ID: ISSN 0027-8424
Publisher:
National Academy of Sciences
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; Science & Technology; reactive oxygen species; oxidative stress; metabolism; protein expression; genome-scale model

Citation Formats

None, None. Cellular responses to reactive oxygen species are predicted from molecular mechanisms. United States: N. p., 2019. Web. doi:10.1073/pnas.1905039116.
None, None. Cellular responses to reactive oxygen species are predicted from molecular mechanisms. United States. doi:10.1073/pnas.1905039116.
None, None. Wed . "Cellular responses to reactive oxygen species are predicted from molecular mechanisms". United States. doi:10.1073/pnas.1905039116.
@article{osti_1577615,
title = {Cellular responses to reactive oxygen species are predicted from molecular mechanisms},
author = {None, None},
abstractNote = {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 prevent cell growth and survival when unmanaged, thus eliciting an essential stress response that is universal and fundamental in biology. Here we develop a computable multiscale description of the ROS stress response in Escherichia coli, called OxidizeME. We use OxidizeME to explain four key responses to oxidative stress: 1) ROS-induced auxotrophy for branched-chain, aromatic, and sulfurous amino acids; 2) nutrient-dependent sensitivity of growth rate to ROS; 3) ROS-specific differential gene expression separate from global growth-associated differential expression; and 4) coordinated expression of iron–sulfur cluster (ISC) and sulfur assimilation (SUF) systems for iron–sulfur cluster biosynthesis. These results show that we can now develop fundamental and quantitative genotype–phenotype relationships for stress responses on a genome-wide basis.},
doi = {10.1073/pnas.1905039116},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = [28],
volume = [116],
place = {United States},
year = {2019},
month = {7}
}

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    Works referencing / citing this record:

    Superoxide Imposes Leakage of Sulfite fromEscherichia coli
    journal, November 1997

    • Benov, Ludmil; Fridovich, Irwin
    • Archives of Biochemistry and Biophysics, Vol. 347, Issue 2
    • DOI: 10.1006/abbi.1997.0343

    Reprint of: Iron/sulfur proteins biogenesis in prokaryotes: Formation, regulation and diversity
    journal, August 2013

    • Roche, Béatrice; Aussel, Laurent; Ezraty, Benjamin
    • Biochimica et Biophysica Acta (BBA) - Bioenergetics, Vol. 1827, Issue 8-9
    • DOI: 10.1016/j.bbabio.2013.05.001

    Bacterial persistence from a system-level perspective
    journal, August 2017

    • Radzikowski, Jakub Leszek; Schramke, Hannah; Heinemann, Matthias
    • Current Opinion in Biotechnology, Vol. 46
    • DOI: 10.1016/j.copbio.2017.02.012

    Evolutionary adaptations that enable enzymes to tolerate oxidative stress
    journal, August 2019


    Modeling the multi-scale mechanisms of macromolecular resource allocation
    journal, October 2018

    • Yang, Laurence; Yurkovich, James T.; King, Zachary A.
    • Current Opinion in Microbiology, Vol. 45
    • DOI: 10.1016/j.mib.2018.01.002

    Genome‐scale models of metabolism and gene expression extend and refine growth phenotype prediction
    journal, January 2013

    • O'Brien, Edward J.; Lerman, Joshua A.; Chang, Roger L.
    • Molecular Systems Biology, Vol. 9, Issue 1
    • DOI: 10.1038/msb.2013.52

    Atmospheric oxygenation three billion years ago
    journal, September 2013

    • Crowe, Sean A.; Døssing, Lasse N.; Beukes, Nicolas J.
    • Nature, Vol. 501, Issue 7468
    • DOI: 10.1038/nature12426

    Potentiating antibacterial activity by predictably enhancing endogenous microbial ROS production
    journal, January 2013

    • Brynildsen, Mark P.; Winkler, Jonathan A.; Spina, Catherine S.
    • Nature Biotechnology, Vol. 31, Issue 2
    • DOI: 10.1038/nbt.2458

    The quantitative and condition-dependent Escherichia coli proteome
    journal, December 2015

    • Schmidt, Alexander; Kochanowski, Karl; Vedelaar, Silke
    • Nature Biotechnology, Vol. 34, Issue 1
    • DOI: 10.1038/nbt.3418

    iML1515, a knowledgebase that computes Escherichia coli traits
    journal, October 2017

    • Monk, Jonathan M.; Lloyd, Colton J.; Brunk, Elizabeth
    • Nature Biotechnology, Vol. 35, Issue 10
    • DOI: 10.1038/nbt.3956

    A domino effect in antifolate drug action in Escherichia coli
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    • Kwon, Yun Kyung; Lu, Wenyun; Melamud, Eugene
    • Nature Chemical Biology, Vol. 4, Issue 10
    • DOI: 10.1038/nchembio.108

    The physiology and habitat of the last universal common ancestor
    journal, July 2016


    The molecular mechanisms and physiological consequences of oxidative stress: lessons from a model bacterium
    journal, May 2013


    Studies of IscR reveal a unique mechanism for metal-dependent regulation of DNA binding specificity
    journal, May 2013

    • Rajagopalan, Senapathy; Teter, Sarah J.; Zwart, Petrus H.
    • Nature Structural & Molecular Biology, Vol. 20, Issue 6
    • DOI: 10.1038/nsmb.2568

    Iron homeostasis in Mycobacterium tuberculosis is essential for persistence
    journal, November 2018


    Reliable and efficient solution of genome-scale models of Metabolism and macromolecular Expression
    journal, January 2017

    • Ma, Ding; Yang, Laurence; Fleming, Ronan M. T.
    • Scientific Reports, Vol. 7, Issue 1
    • DOI: 10.1038/srep40863

    The iron-sulfur clusters of dehydratases are primary intracellular targets of copper toxicity
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    • Macomber, L.; Imlay, J. A.
    • Proceedings of the National Academy of Sciences, Vol. 106, Issue 20
    • DOI: 10.1073/pnas.0812808106

    A role for tetrahydrofolates in the metabolism of iron-sulfur clusters in all domains of life
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    • Waller, J. C.; Alvarez, S.; Naponelli, V.
    • Proceedings of the National Academy of Sciences, Vol. 107, Issue 23
    • DOI: 10.1073/pnas.0911586107

    Iron enzyme ribulose-5-phosphate 3-epimerase in Escherichia coli is rapidly damaged by hydrogen peroxide but can be protected by manganese
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    • Sobota, J. M.; Imlay, J. A.
    • Proceedings of the National Academy of Sciences, Vol. 108, Issue 13
    • DOI: 10.1073/pnas.1100410108

    Thermosensitivity of growth is determined by chaperone-mediated proteome reallocation
    journal, October 2017

    • Chen, Ke; Gao, Ye; Mih, Nathan
    • Proceedings of the National Academy of Sciences, Vol. 114, Issue 43
    • DOI: 10.1073/pnas.1705524114

    NADPH: ferredoxin oxidoreductase acts as a paraquat diaphorase and is a member of the soxRS regulon.
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    • Liochev, S. I.; Hausladen, A.; Beyer, W. F.
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    • DOI: 10.1073/pnas.91.4.1328

    The Mechanism of the Auxotrophy for Sulfur-containing Amino Acids Imposed upon Escherichia coli by Superoxide
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    • Benov, Ludmil; Kredich, Nicholas M.; Fridovich, Irwin
    • Journal of Biological Chemistry, Vol. 271, Issue 35
    • DOI: 10.1074/jbc.271.35.21037

    Why Superoxide Imposes an Aromatic Amino Acid Auxotrophy on Escherichia coli : THE TRANSKETOLASE CONNECTION
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    • Benov, Ludmil; Fridovich, Irwin
    • Journal of Biological Chemistry, Vol. 274, Issue 7
    • DOI: 10.1074/jbc.274.7.4202

    ALEdb 1.0: a database of mutations from adaptive laboratory evolution experimentation
    journal, October 2018

    • Phaneuf, Patrick V.; Gosting, Dennis; Palsson, Bernhard O.
    • Nucleic Acids Research, Vol. 47, Issue D1
    • DOI: 10.1093/nar/gky983

    Oxidative stress and disruption of labile iron generate specific auxotrophic requirements in Salmonella enterica
    journal, January 2009


    Where in the world do bacteria experience oxidative stress?: Oxidative stress in natural environments
    journal, November 2018


    Iron-sulphur clusters and the problem with oxygen
    journal, February 2006


    A role of ygfZ in the Escherichia coli response to plumbagin challenge
    journal, January 2010

    • Lin, Ching-Nan; Syu, Wan-Jr; Sun, Wei-Sheng W.
    • Journal of Biomedical Science, Vol. 17, Issue 1
    • DOI: 10.1186/1423-0127-17-84

    solveME: fast and reliable solution of nonlinear ME models
    journal, September 2016


    DynamicME: dynamic simulation and refinement of integrated models of metabolism and protein expression
    journal, January 2019


    COBRAme: A computational framework for genome-scale models of metabolism and gene expression
    journal, July 2018


    Multiscale Modeling of Metabolism and Macromolecular Synthesis in E. coli and Its Application to the Evolution of Codon Usage
    journal, September 2012


    Escherichia coli RIC Is Able to Donate Iron to Iron-Sulfur Clusters
    journal, April 2014


    Bacterial persistence is an active σ S stress response to metabolic flux limitation
    journal, September 2016

    • Radzikowski, Jakub Leszek; Vedelaar, Silke; Siegel, David
    • Molecular Systems Biology, Vol. 12, Issue 9
    • DOI: 10.15252/msb.20166998