Restoration of fitness lost due to dysregulation of the pyruvate dehydrogenase complex is triggered by ribosomal binding site modifications

• DOI: 10.1016/j.celrep.2021.108961
• Publication Date: 2021-04-06T15:41:53Z
• Authors: Amitesh Anand; Connor A. Olson; Anand V. Sastry; Arjun Patel; Richard Szubin; Laurence Yang; Adam M. Feist; Bernhard O. Palsson
• Keywords: Flux Balance Analysis

Pyruvate dehydrogenase complex (PDC) functions as the main determinant of respiro-fermentative balance because it converts pyruvate to acetyl-coenzyme A (CoA), which then enters TCA (tricarboxylic acid cycle). PDC is repressed by regulator (PdhR) in Escherichia coli. The deletion pdhR gene compromises fitness aerobic environments. We evolve E. coli strain examine its achievable growth rate and underlying adaptive strategies. find that (1) optimal proteome allocation critical achieving rate; (2) expression evolved strains reduced through mutations Shine-Dalgarno sequence; (3) rewiring flux increased reactive oxygen species (ROS) defense occur strains; (4) adapt an efficient biomass yield. Together, these results show how adaptation can alternative regulatory mechanisms for a key cellular process if primary mode fails.