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

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.

Tuning of the Carbon-to-Nitrogen Ratio for the Production of l-Arginine by Escherichia coli

“…In the three cases, no L-arginine production was detected, showing that glutamate is not suitable as the sole nitrogen source. Poor growth of a variety of E. coli strains on glucose when glutamate (at about 1.5 g/L) was the sole nitrogen source has been reported in a recent study [38]. It has been observed that under those conditions, TCA cycle intermediates accumulate, leading to the inhibition of the signalling molecule cAMP levels, thereby impairing cell growth.…”

“…These results therefore indicate that a C/N ratio of 12 provides insufficient nitrogen for efficient fermentation. In the fermentation with 30 g/L glucose, the cells used the remaining glucose after cell growth and L-arginine production stopped, likely due to utilization of L-arginine as a poor nitrogen source (L-arginine concentration is decreasing) [38], and only acetate was produced. In the fermentation with 15 g/L glucose, neither glucose uptake nor acetate production occurred after ammonia depletion.…”

Optimality and sub-optimality in a bacterial growth law

“…One prediction from this picture is that the growth rate is optimal under all conditions that respect the growth laws and that sub-optimal resource allocation only occurs, when cells deviate from these laws. Previous studies identified conditions of sub-optimal growth in E. coli , but did not address this sub-optimality in the context of growth laws131415 or focused specifically on conditions that do not follow the growth law16, so that it remains unclear whether growth laws maximize the growth rate. A second possible explanation for growth laws is that they are practical heuristics: the growth law line is determined by cellular regulation and not by optimality constraints.…”

The Small Protein SgrT Controls Transport Activity of the Glucose-Specific Phosphotransferase System

“…Under most circumstances, glucose is a preferred carbon source for Escherichia coli, yet under some conditions, metabolic flux becomes suboptimal, and glucose transport and metabolism are disfavored (1,2). One condition of impaired glucose metabolism occurs when cells are exposed to nonmetabolizable glucose analogs (e.g., ␣-methylglucoside [␣MG]) that are taken up and phosphorylated but cannot be metabolized further.…”

“…A previous study demonstrated that the IIC Glc domain of PtsG most likely confers substrate specificity for glucose. In that study, a chimeric transporter composed of the PtsG 2 , and the total number of spots was determined and plotted as heat maps. Cells are combined from two independent experiments.…”