Cellular responses to reactive oxygen species are predicted from molecular mechanisms

Laurence Yang, Nathan Mih, Amitesh Anand, Joon Ho Park, Justin Tan, James T. Yurkovich, Jonathan M. Monk, Colton J. Lloyd, Troy E. Sandberg, Sang Woo Seo, Donghyuk Kim, Anand V. Sastry, Patrick Phaneuf, Ye Gao, Jared T. Broddrick, Ke Chen, David Heckmann, Richard Szubin, Ying Hefner, Adam M. Feist & 1 others Bernhard O. Palsson

Research output: Contribution to journalJournal articleResearchpeer-review

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.
Original languageEnglish
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number28
Pages (from-to)14368-14373
ISSN0027-8424
DOIs
Publication statusPublished - 2019

Keywords

  • Reactive oxygen species
  • Oxidative stress
  • Metabolism
  • Protein expression
  • Genome-scale model

Cite this

Yang, Laurence ; Mih, Nathan ; Anand, Amitesh ; Park, Joon Ho ; Tan, Justin ; Yurkovich, James T. ; Monk, Jonathan M. ; Lloyd, Colton J. ; Sandberg, Troy E. ; Seo, Sang Woo ; Kim, Donghyuk ; Sastry, Anand V. ; Phaneuf, Patrick ; Gao, Ye ; Broddrick, Jared T. ; Chen, Ke ; Heckmann, David ; Szubin, Richard ; Hefner, Ying ; Feist, Adam M. ; Palsson, Bernhard O. / Cellular responses to reactive oxygen species are predicted from molecular mechanisms. In: Proceedings of the National Academy of Sciences of the United States of America. 2019 ; Vol. 116, No. 28. pp. 14368-14373.
@article{19c21dd246184a17a4e0deb8fbe383bd,
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.",
keywords = "Reactive oxygen species, Oxidative stress, Metabolism, Protein expression, Genome-scale model",
author = "Laurence Yang and Nathan Mih and Amitesh Anand and Park, {Joon Ho} and Justin Tan and Yurkovich, {James T.} and Monk, {Jonathan M.} and Lloyd, {Colton J.} and Sandberg, {Troy E.} and Seo, {Sang Woo} and Donghyuk Kim and Sastry, {Anand V.} and Patrick Phaneuf and Ye Gao and Broddrick, {Jared T.} and Ke Chen and David Heckmann and Richard Szubin and Ying Hefner and Feist, {Adam M.} and Palsson, {Bernhard O.}",
year = "2019",
doi = "10.1073/pnas.1905039116",
language = "English",
volume = "116",
pages = "14368--14373",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "The National Academy of Sciences of the United States of America",
number = "28",

}

Yang, L, Mih, N, Anand, A, Park, JH, Tan, J, Yurkovich, JT, Monk, JM, Lloyd, CJ, Sandberg, TE, Seo, SW, Kim, D, Sastry, AV, Phaneuf, P, Gao, Y, Broddrick, JT, Chen, K, Heckmann, D, Szubin, R, Hefner, Y, Feist, AM & Palsson, BO 2019, 'Cellular responses to reactive oxygen species are predicted from molecular mechanisms', Proceedings of the National Academy of Sciences of the United States of America, vol. 116, no. 28, pp. 14368-14373. https://doi.org/10.1073/pnas.1905039116

Cellular responses to reactive oxygen species are predicted from molecular mechanisms. / Yang, Laurence; Mih, Nathan; Anand, Amitesh; Park, Joon Ho; Tan, Justin; Yurkovich, James T.; Monk, Jonathan M.; Lloyd, Colton J.; Sandberg, Troy E.; Seo, Sang Woo; Kim, Donghyuk; Sastry, Anand V.; Phaneuf, Patrick; Gao, Ye; Broddrick, Jared T.; Chen, Ke; Heckmann, David; Szubin, Richard; Hefner, Ying; Feist, Adam M.; Palsson, Bernhard O.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 116, No. 28, 2019, p. 14368-14373.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Cellular responses to reactive oxygen species are predicted from molecular mechanisms

AU - Yang, Laurence

AU - Mih, Nathan

AU - Anand, Amitesh

AU - Park, Joon Ho

AU - Tan, Justin

AU - Yurkovich, James T.

AU - Monk, Jonathan M.

AU - Lloyd, Colton J.

AU - Sandberg, Troy E.

AU - Seo, Sang Woo

AU - Kim, Donghyuk

AU - Sastry, Anand V.

AU - Phaneuf, Patrick

AU - Gao, Ye

AU - Broddrick, Jared T.

AU - Chen, Ke

AU - Heckmann, David

AU - Szubin, Richard

AU - Hefner, Ying

AU - Feist, Adam M.

AU - Palsson, Bernhard O.

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

KW - Reactive oxygen species

KW - Oxidative stress

KW - Metabolism

KW - Protein expression

KW - Genome-scale model

U2 - 10.1073/pnas.1905039116

DO - 10.1073/pnas.1905039116

M3 - Journal article

VL - 116

SP - 14368

EP - 14373

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 28

ER -