Glucose becomes one of the worst carbon sources for E.coli on poor nitrogen sources due to suboptimal levels of cAMP

• Published in: Scientific reports Vol. 6; no. 1; p. 24834
• Main Authors: Bren, Anat, Park, Junyoung O., Towbin, Benjamin D., Dekel, Erez, Rabinowitz, Joshua D., Alon, Uri
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25-04-2016; Nature Publishing Group
• Subjects: 38; 38/35; 49/56; 631/326; 631/553/2710; 8-Bromo Cyclic Adenosine Monophosphate - analogs & derivatives; 8-Bromo Cyclic Adenosine Monophosphate - chemistry; 8-Bromo Cyclic Adenosine Monophosphate - metabolism; Amino acids; Arginine; Carbohydrate Metabolism; Carbohydrates - chemistry; Carbon - chemistry; Carbon sources; Citric Acid Cycle; Cyclic AMP; Cyclic AMP - metabolism; E coli; Energy Metabolism; Escherichia coli - growth & development; Escherichia coli - metabolism; Glucose; Glucose - chemistry; Glucose - metabolism; Growth rate; Humanities and Social Sciences; Ketoglutaric acid; Ketoglutaric Acids - chemistry; Ketoglutaric Acids - metabolism; Metabolites; multidisciplinary; Nitrogen; Nitrogen sources; Proline; Science; Sugar
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep24834

In most conditions, glucose is the best carbon source for
E. coli:
it provides faster growth than other sugars and is consumed first in sugar mixtures. Here we identify conditions in which
E. coli
strains grow slower on glucose than on other sugars, namely when a single amino acid (arginine, glutamate, or proline) is the sole nitrogen source. In sugar mixtures with these nitrogen sources,
E. coli
still consumes glucose first, but grows faster rather than slower after exhausting glucose, generating a reversed diauxic shift. We trace this counterintuitive behavior to a metabolic imbalance: levels of TCA-cycle metabolites including α-ketoglutarate are high and levels of the key regulatory molecule cAMP are low. Growth rates were increased by experimentally increasing cAMP levels, either by adding external cAMP, by genetically perturbing the cAMP circuit or by inhibition of glucose uptake. Thus, the cAMP control circuitry seems to have a ‘bug’ that leads to slow growth under what may be an environmentally rare condition.