Cellular responses to reactive oxygen species are predicted from molecular mechanisms.

Autor:	Yang L; Department of Bioengineering, University of California San Diego, La Jolla, CA 92093; lyang@eng.ucsd.edu palsson@ucsd.edu., Mih N; Department of Nanoengineering, University of California San Diego, La Jolla, CA 92093.; Bioinformatics and Systems Biology Program, University of California San Diego, La Jolla, CA 92093., Anand A; Department of Bioengineering, University of California San Diego, La Jolla, CA 92093., Park JH; Department of Nanoengineering, University of California San Diego, La Jolla, CA 92093., Tan J; Department of Bioengineering, University of California San Diego, La Jolla, CA 92093., Yurkovich JT; Department of Bioengineering, University of California San Diego, La Jolla, CA 92093.; Bioinformatics and Systems Biology Program, University of California San Diego, La Jolla, CA 92093., Monk JM; Department of Bioengineering, University of California San Diego, La Jolla, CA 92093., Lloyd CJ; Department of Bioengineering, University of California San Diego, La Jolla, CA 92093., Sandberg TE; Department of Bioengineering, University of California San Diego, La Jolla, CA 92093., Seo SW; Department of Bioengineering, University of California San Diego, La Jolla, CA 92093., Kim D; Department of Bioengineering, University of California San Diego, La Jolla, CA 92093., Sastry AV; Department of Bioengineering, University of California San Diego, La Jolla, CA 92093., Phaneuf P; Bioinformatics and Systems Biology Program, University of California San Diego, La Jolla, CA 92093., Gao Y; Division of Biological Sciences, University of California San Diego, La Jolla, CA 92093., Broddrick JT; Division of Biological Sciences, University of California San Diego, La Jolla, CA 92093., Chen K; Department of Bioengineering, University of California San Diego, La Jolla, CA 92093., Heckmann D; Department of Bioengineering, University of California San Diego, La Jolla, CA 92093., Szubin R; Department of Bioengineering, University of California San Diego, La Jolla, CA 92093., Hefner Y; Department of Bioengineering, University of California San Diego, La Jolla, CA 92093., Feist AM; Department of Bioengineering, University of California San Diego, La Jolla, CA 92093.; The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800 Kongens Lyngby, Denmark., Palsson BO; Department of Bioengineering, University of California San Diego, La Jolla, CA 92093; lyang@eng.ucsd.edu palsson@ucsd.edu.; The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800 Kongens Lyngby, Denmark.; Department of Pediatrics, University of California San Diego, La Jolla, CA 92093.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2019 Jul 09; Vol. 116 (28), pp. 14368-14373. Date of Electronic Publication: 2019 Jul 03.
DOI:	10.1073/pnas.1905039116
Abstrakt:	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. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
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