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Deciphering the physiological response of Escherichia coli under high ATP demand

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 fin...

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Autores principales: Boecker, Simon, Slaviero, Giulia, Schramm, Thorben, Szymanski, Witold, Steuer, Ralf, Link, Hannes, Klamt, Steffen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8686765/
https://www.ncbi.nlm.nih.gov/pubmed/34928538
http://dx.doi.org/10.15252/msb.202110504
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author Boecker, Simon
Slaviero, Giulia
Schramm, Thorben
Szymanski, Witold
Steuer, Ralf
Link, Hannes
Klamt, Steffen
author_facet Boecker, Simon
Slaviero, Giulia
Schramm, Thorben
Szymanski, Witold
Steuer, Ralf
Link, Hannes
Klamt, Steffen
author_sort Boecker, Simon
collection PubMed
description 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.
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spelling pubmed-86867652022-01-04 Deciphering the physiological response of Escherichia coli under high ATP demand Boecker, Simon Slaviero, Giulia Schramm, Thorben Szymanski, Witold Steuer, Ralf Link, Hannes Klamt, Steffen Mol Syst Biol Articles 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. John Wiley and Sons Inc. 2021-12-20 /pmc/articles/PMC8686765/ /pubmed/34928538 http://dx.doi.org/10.15252/msb.202110504 Text en © 2021 The Authors Published under the terms of the CC BY 4.0 license https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Articles
Boecker, Simon
Slaviero, Giulia
Schramm, Thorben
Szymanski, Witold
Steuer, Ralf
Link, Hannes
Klamt, Steffen
Deciphering the physiological response of Escherichia coli under high ATP demand
title Deciphering the physiological response of Escherichia coli under high ATP demand
title_full Deciphering the physiological response of Escherichia coli under high ATP demand
title_fullStr Deciphering the physiological response of Escherichia coli under high ATP demand
title_full_unstemmed Deciphering the physiological response of Escherichia coli under high ATP demand
title_short Deciphering the physiological response of Escherichia coli under high ATP demand
title_sort deciphering the physiological response of escherichia coli under high atp demand
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8686765/
https://www.ncbi.nlm.nih.gov/pubmed/34928538
http://dx.doi.org/10.15252/msb.202110504
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