RRC ID 59070
Author Zampieri M, Hörl M, Hotz F, Müller NF, Sauer U.
Title Regulatory mechanisms underlying coordination of amino acid and glucose catabolism in Escherichia coli.
Journal Nat Commun
Abstract How microbes dynamically coordinate uptake and simultaneous utilization of nutrients in complex nutritional ecosystems is still an open question. Here, we develop a constraint-based modeling approach that exploits non-targeted exo-metabolomics data to unravel adaptive decision-making processes in dynamic nutritional environments. We thereby investigate metabolic adaptation of Escherichia coli to continuously changing conditions during batch growth in complex medium. Unexpectedly, model-based analysis of time resolved exo-metabolome data revealed that fastest growth coincides with preferred catabolism of amino acids, which, in turn, reduces glucose uptake and increases acetate overflow. We show that high intracellular levels of the amino acid degradation metabolites pyruvate and oxaloacetate can directly inhibit the phosphotransferase system (PTS), and reveal their functional role in mediating regulatory decisions for uptake and catabolism of alternative carbon sources. Overall, the proposed methodology expands the spectrum of possible applications of flux balance analysis to decipher metabolic adaptation mechanisms in naturally occurring habitats and diverse organisms.
Volume 10(1)
Pages 3354
Published 2019-7-26
DOI 10.1038/s41467-019-11331-5
PII 10.1038/s41467-019-11331-5
PMID 31350417
PMC PMC6659692
MeSH Acetates / metabolism Amino Acids / metabolism* Escherichia coli / genetics Escherichia coli / growth & development Escherichia coli / metabolism* Escherichia coli Proteins / genetics Escherichia coli Proteins / metabolism Gene Expression Regulation, Bacterial Glucose / metabolism* Oxaloacetic Acid / metabolism Phosphotransferases / genetics Phosphotransferases / metabolism Pyruvic Acid / metabolism
IF 11.878
Times Cited 2
Prokaryotes E. coli ASKA library strain b2416