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

Open Biology

Ankita Pal¹  K. V. Venkatesh¹  Sumana Srinivasan¹  Mahesh S. Iyer¹  Aswin Sai Narain Seshasayee² 

[1] Department of Chemical Engineering, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India;National Centre for Biological Sciences, GKVK, Bellary Road, Bangalore 560065, India;

关键词: adaptive evolution;    cAMP receptor protein;    pleiotropic effects;    exponential growth;    intracellular metabolites;   

DOI  :  10.1098/rsob.210206

来源: DOAJ

【 摘 要 】

Evolution facilitates emergence of fitter phenotypes by efficient allocation of cellular resources in conjunction with beneficial mutations. However, system-wide pleiotropic effects that redress the perturbations to the apex node of the transcriptional regulatory networks remain unclear. Here, we elucidate that absence of global transcriptional regulator CRP in Escherichia coli results in alterations in key metabolic pathways under glucose respiratory conditions, favouring stress- or hedging-related functions over growth-enhancing functions. Further, we disentangle the growth-mediated effects from the CRP regulation-specific effects on these metabolic pathways. We quantitatively illustrate that the loss of CRP perturbs proteome efficiency, as evident from metabolic as well as ribosomal proteome fractions, that corroborated with intracellular metabolite profiles. To address how E. coli copes with such systemic defect, we evolved Δcrp mutant in the presence of glucose. Besides acquiring mutations in the promoter of glucose transporter ptsG, the evolved populations recovered the metabolic pathways to their pre-perturbed state coupled with metabolite re-adjustments, which altogether enabled increased growth. By contrast to Δcrp mutant, the evolved strains remodelled their proteome efficiency towards biomass synthesis, albeit at the expense of carbon efficiency. Overall, we comprehensively illustrate the genetic and metabolic basis of pleiotropic effects, fundamental for understanding the growth physiology.

【 授权许可】

Unknown