Decoding the Genome-Wide Regulatory Landscape of Escherichia coli in Response to Various Environmental Stresses

Understanding the genome-wide regulatory network in response to environmental stress is prerequisite to rationally design microbes surviving against stresses such as metal iron depletion, oxidative stress, low pH stress, and osmotic stress. However, the full regulatory potential of microbes remains undefined. Here, we comprehensively reconstructed transcriptional regulatory networks of several transcription factors related to iron depletion, oxidative stress, low pH stress, and osmotic stress in Escherichia coli K-12 MG1655 by using genome-wide measurements. Integrative data analysis revealed that each transcription factor exhibits complex role in many fundamental cellular processes to coordinately respond to iron starvation stress, low pH stress, oxidative stress, and osmotic stress as well. These types of new knowledges can be further utilized to find proper engineering targets to improve cellular tolerance towards theses stresses. Also, we believe that the incorporation of these types of comprehensive operon structures that account for cellular regulation along with regulatory network into current computational model would make it possible to mechanistically model and predict the complex regulatory interactions and thus allow us to more accurately compute complex phenotypes and design genomes for synthetic cells in the future.