Journal article
Restoration of fitness lost due to dysregulation of the pyruvate dehydrogenase complex is triggered by ribosomal binding site modifications
Pyruvate dehydrogenase complex (PDC) functions as the main determinant of the respiro-fermentative balance because it converts pyruvate to acetyl-coenzyme A (CoA), which then enters the TCA (tricarboxylic acid cycle). PDC is repressed by the pyruvate dehydrogenase complex regulator (PdhR) in Escherichia coli.
The deletion of the pdhR gene compromises fitness in aerobic environments. We evolve the E. coli pdhR deletion strain to examine its achievable growth rate and the underlying adaptive strategies. We find that (1) optimal proteome allocation to PDC is critical in achieving optimal growth rate; (2) expression of PDC in evolved strains is reduced through mutations in the Shine-Dalgarno sequence; (3) rewiring of the TCA flux and increased reactive oxygen species (ROS) defense occur in the evolved strains; and (4) the evolved strains adapt to an efficient biomass yield.
Together, these results show how adaptation can find alternative regulatory mechanisms for a key cellular process if the primary regulatory mode fails.
Language: | English |
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Publisher: | Elsevier |
Year: | 2021 |
Pages: | 108961-108961 |
ISSN: | 22111247 |
Types: | Journal article |
DOI: | 10.1016/j.celrep.2021.108961 |
ORCIDs: | 0000-0002-3720-4301 , 0000-0003-1959-0445 and Palsson, Bernhard O. |
Adaptive laboratory evolution Bioenergetics Proteome allocation System biology Transcriptional regulatory network
Binding Sites Biology (General) Citric Acid Cycle Electrons Escherichia coli Escherichia coli Proteins Glycolysis Homeostasis Oxidation-Reduction Pyruvate Dehydrogenase Complex Pyruvic Acid QH301-705.5 Ribosomes Transcription, Genetic adaptive laboratory evolution bioenergetics proteome allocation system biology transcriptional regulatory network