Journal article
Multiple Optimal Phenotypes Overcome Redox and Glycolytic Intermediate Metabolite Imbalances in Escherichia coli pgi Knockout Evolutions
Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark1
Network Reconstruction in Silico Biology, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark2
iLoop, Translational Management, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark3
University of California at San Diego4
ALE Technology & Software Development, Research Groups, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark5
Big Data 2 Knowledge, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark6
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.
Language: | English |
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Publisher: | American Society for Microbiology |
Year: | 2018 |
Pages: | e00823-18-e00823-18 |
ISSN: | 10985336 and 00992240 |
Types: | Journal article |
DOI: | 10.1128/AEM.00823-18 |
ORCIDs: | Feist, Adam M. and Palsson, Bernhard O. |