Global pleiotropic effects in adaptively evolved Escherichia coli lacking CRP reveal molecular mechanisms that define growth physiology

Abstract

Evolution entails the orchestration of cellular resources together with mutations to achieve fitter phenotypes. Here, we determined the system-wide pleiotropic effects that redress the significant perturbations caused by the deletion of global transcriptional regulator CRP in Escherichia coli when evolved in the presence of glucose. We elucidated that absence of CRP results in alterations in key metabolic pathways instrumental for the precise functioning of protein biosynthesis machinery that subsequently corroborated with intracellular metabolite profiles. Apart from acquiring mutations in the promoter of glucose transporter ptsG, the evolved populations recovered the metabolic pathways to their pre-perturbed state with amelioration of protein biosynthesis machinery coupled with fine-tuned proteome re-allocation that enabled growth recovery. However, ineffective utilization of carbon towards biomass as perceived from ATP maintenance flux and costly amino acid accumulations poses a limitation. Overall, we comprehensively illustrate the genetic and metabolic adjustments underlying adaptive evolvability, fundamental for understanding the growth physiology.