Emerging Discipline of Structural Systems Biology Reveals E. coli Heat Tolerance


Microbial sensitivity to heat, or thermosensitivity, depends on the stability of cellular proteins and their ability to remain in an active, folded state. Research to improve microbial survival and function at higher temperatures has mainly focused on strategies for increasing the structural stability of individual proteins. A new approach called structural systems biology directly assesses the genome-scale metabolic potential of a model organism, E. coli, for thermostability. Using this approach, metabolic reactions of E. coli were integrated with three-dimensional structures of each catalytic enzyme. To simulate E. coli growth at various temperatures, protein (structural) activity functions were defined to impose temperature constraints on the metabolic models. This combined metabolic-structural method allows researchers to integrate temperature-dependent information about enzyme function with simulations of microbial metabolic growth. This approach enabled simulation of E. coli growth under various temperature conditions that was in good agreement with experimental growth data. It also provided mechanistic interpretations of mutations that conferred greater thermostability in E. coli. This new approach has important implications for developing industrial microbes as biocatalysts.


Chang, R. L., K. Andrews, D. Kim, Z. Li, A. Godzik, and B. O. Palsson. 2013. “Structural Systems Biology Evaluation of Metabolic Thermotolerance in Escherichia coli,” Science 340, 1220–23. DOI: 10.1126/science/1234012.