Glucose becomes one of the worst carbon sources for E.coli on poor nitrogen sources due to suboptimal levels of cAMP. Author Anat Bren, Junyoung Park, Benjamin Towbin, Erez Dekel, Joshua Rabinowitz, Uri Alon Publication Year 2016 Type Journal Article Abstract 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. Keywords Escherichia coli, Cyclic AMP, Glucose, Carbohydrate Metabolism, Carbohydrates, Citric Acid Cycle, Energy Metabolism, Carbon, Ketoglutaric Acids, 8-Bromo Cyclic Adenosine Monophosphate Journal Sci Rep Volume 6 Pages 24834 Date Published 2016 Apr 25 ISSN Number 2045-2322 DOI 10.1038/srep24834 Alternate Journal Sci Rep PMCID PMC4843011 PMID 27109914 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML