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:

None, None

Publication Date:

2019-07-03

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