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 inEscherichia 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:
-
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- Univ. of California San Diego, La Jolla, CA (United States)
- Univ. of California San Diego, La Jolla, CA (United States); Technical Univ. of Denmark, Lyngby (Denmark)
- Publication Date:
- Research Org.:
- Lawrence Berkeley National Lab. (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
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., and Palsson, Bernhard O. Cellular responses to reactive oxygen species are predicted from molecular mechanisms. United States: N. p., 2019.
Web. doi:10.1073/pnas.1905039116.
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. United States. https://doi.org/10.1073/pnas.1905039116
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., and Palsson, Bernhard O. Wed .
"Cellular responses to reactive oxygen species are predicted from molecular mechanisms". United States. https://doi.org/10.1073/pnas.1905039116. https://www.osti.gov/servlets/purl/1577615.
@article{osti_1577615,
title = {Cellular responses to reactive oxygen species are predicted from molecular mechanisms},
author = {Yang, Laurence and Mih, Nathan and Anand, Amitesh and Park, Joon Ho and Tan, Justin and Yurkovich, James T. and Monk, Jonathan M. and Lloyd, Colton J. and Sandberg, Troy E. and Seo, Sang Woo and Kim, Donghyuk and Sastry, Anand V. and Phaneuf, Patrick and Gao, Ye and Broddrick, Jared T. and Chen, Ke and Heckmann, David and Szubin, Richard and Hefner, Ying and Feist, Adam M. and Palsson, Bernhard O.},
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 inEscherichia 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}
}
Web of Science
Figures / Tables:

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