Deciphering the physiological response of Escherichia coli under high ATP demand

Molecular Systems Biology

Simon Boecker¹  Giulia Slaviero¹  Steffen Klamt¹  Witold Szymanski²  Thorben Schramm³  Hannes Link³  Ralf Steuer⁴ 

[1] Analysis and Redesign of Biological Networks Max Planck Institute for Dynamics of Complex Technical Systems Magdeburg Germany;Core Facility for Mass Spectrometry and Proteomics Max Planck Institute for Terrestrial Microbiology Marburg Germany;Dynamic Control of Metabolic Networks Max Planck Institute for Terrestrial Microbiology Marburg Germany;Institute for Biology Humboldt‐University of Berlin Berlin Germany;

关键词: ATP homeostasis;    central metabolism;    glycolysis;    kinetic model;    metabolic engineering;   

DOI  :  10.15252/msb.202110504

来源: DOAJ

【 摘 要 】

Abstract One long‐standing question in microbiology is how microbes buffer perturbations in energy metabolism. In this study, we systematically analyzed the impact of different levels of ATP demand in Escherichia coli under various conditions (aerobic and anaerobic, with and without cell growth). One key finding is that, under all conditions tested, the glucose uptake increases with rising ATP demand, but only to a critical level beyond which it drops markedly, even below wild‐type levels. Focusing on anaerobic growth and using metabolomics and proteomics data in combination with a kinetic model, we show that this biphasic behavior is induced by the dual dependency of the phosphofructokinase on ATP (substrate) and ADP (allosteric activator). This mechanism buffers increased ATP demands by a higher glycolytic flux but, as shown herein, it collapses under very low ATP concentrations. Model analysis also revealed two major rate‐controlling steps in the glycolysis under high ATP demand, which could be confirmed experimentally. Our results provide new insights on fundamental mechanisms of bacterial energy metabolism and guide the rational engineering of highly productive cell factories.

【 授权许可】

Unknown