Multiple Optimal Phenotypes Overcome Redox and Glycolytic Intermediate Metabolite Imbalances in Escherichia coli pgi Knockout Evolutions

Douglas McCloskey, Sibei Xu, Troy E. Sandberg, Elizabeth Brunk, Ying Hefner, Richard Szubin, Adam M. Feist, Bernhard O. Palsson*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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A mechanistic understanding of how new phenotypes develop to overcome the loss of a gene product provides valuable insight on both the metabolic and regulatory functions of the lost gene. The pgi gene, whose product catalyzes the second step in glycolysis, was deleted in a growth-optimized Escherichia coli K-12 MG1655 strain. The initial knockout (KO) strain exhibited an 80% drop in growth rate that was largely recovered in eight replicate, but phenotypically distinct, cultures after undergoing adaptive laboratory evolution (ALE). Multi-omic data sets showed that the loss of pgi substantially shifted pathway usage, leading to a redox and sugar phosphate stress response. These stress responses were overcome by unique combinations of innovative mutations selected for by ALE. Thus, the coordinated mechanisms from genome to metabolome that lead to multiple optimal phenotypes after the loss of a major gene product were revealed.
Original languageEnglish
Article numbere00823-18
JournalApplied and Environmental Microbiology
Issue number19
Number of pages17
Publication statusPublished - 2018


  • Escherichia coli
  • Adaptive laboratory evolution
  • Multi-omics analysis
  • Mutation analysis
  • pgi gene knockout
  • Systems biology

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