Glucose becomes one of the worst carbon sources for E.coli on poor nitrogen sources due to suboptimal levels of cAMP.
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.
Dept. of Molecular Cell Biology, Weizmann Institute of Science, Rehovot Israel 76100.
Anat
A
Bren
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.|Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA.
Junyoung O
JO
Park
Dept. of Molecular Cell Biology, Weizmann Institute of Science, Rehovot Israel 76100.
Benjamin D
BD
Towbin
Dept. of Molecular Cell Biology, Weizmann Institute of Science, Rehovot Israel 76100.
Erez
E
Dekel
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.|Department of Chemistry, Princeton University, Princeton, NJ 08544, USA.
Joshua D
JD
Rabinowitz
Dept. of Molecular Cell Biology, Weizmann Institute of Science, Rehovot Israel 76100.
Uri
U
Alon
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D050260:Carbohydrate Metabolism; D002241:Carbohydrates / Q000737:chemistry*; D002244:Carbon / Q000737:chemistry; D002952:Citric Acid Cycle; D000242:Cyclic AMP / Q000378:metabolism; D004734:Energy Metabolism; D004926:Escherichia coli / Q000254:growth & development / Q000378:metabolism*; D005947:Glucose / Q000737:chemistry / Q000378:metabolism*; D007656:Ketoglutaric Acids / Q000737:chemistry / Q000378:metabolism*
D002241:Carbohydrates; D007656:Ketoglutaric Acids; D015124:8-Bromo Cyclic Adenosine Monophosphate; D002244:Carbon; C044258:8-chloro-cyclic adenosine monophosphate; D000242:Cyclic AMP; D005947:Glucose