Acetate overflow metabolism regulates a major metabolic shift after glucose depletion in Escherichia coli

FEBS Letters ◽  
2021 ◽  
Author(s):  
Tomohiro Shimada ◽  
Kohta Nakazawa ◽  
Tomoyuki Tachikawa ◽  
Natsumi Saito ◽  
Tatsuya Niwa ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Overflow Metabolism ◽  
Metabolic Shift ◽  
Glucose Depletion ◽  
Acetate Overflow

scholarly journals Control and regulation of acetate overflow in Escherichia coli

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Pierre Millard ◽  
Brice Enjalbert ◽  
Sandrine Uttenweiler-Joseph ◽  
Jean-Charles Portais ◽  
Fabien Létisse
Keyword(s):  
Escherichia Coli ◽  
Glucose Metabolism ◽  
Kinetic Model ◽  
Local Control ◽  
Overflow Metabolism ◽  
Central Metabolism ◽  
Global Regulator ◽  
E Coli ◽  
By Products ◽  
Acetate Overflow

Overflow metabolism refers to the production of seemingly wasteful by-products by cells during growth on glucose even when oxygen is abundant. Two theories have been proposed to explain acetate overflow in Escherichia coli – global control of the central metabolism and local control of the acetate pathway – but neither accounts for all observations. Here, we develop a kinetic model of E. coli metabolism that quantitatively accounts for observed behaviours and successfully predicts the response of E. coli to new perturbations. We reconcile these theories and clarify the origin, control, and regulation of the acetate flux. We also find that, in turns, acetate regulates glucose metabolism by coordinating the expression of glycolytic and TCA genes. Acetate should not be considered a wasteful end-product since it is also a co-substrate and a global regulator of glucose metabolism in E. coli. This has broad implications for our understanding of overflow metabolism.

scholarly journals Control and regulation of acetate overflow in Escherichia coli

2020 ◽  
Author(s):  
Pierre Millard ◽  
Brice Enjalbert ◽  
Sandrine Uttenweiler-Joseph ◽  
Jean-Charles Portais ◽  
Fabien Létisse
Keyword(s):  
Escherichia Coli ◽  
Glucose Metabolism ◽  
Kinetic Model ◽  
Local Control ◽  
Overflow Metabolism ◽  
Central Metabolism ◽  
Global Regulator ◽  
E Coli ◽  
By Products ◽  
Acetate Overflow

AbstractOverflow metabolism refers to the production of seemingly wasteful by-products by cells during growth on glucose even when oxygen is abundant. Two theories have been proposed to explain acetate overflow in Escherichia coli – global control of the central metabolism and local control of the acetate pathway – but neither accounts for all observations. Here, we develop a kinetic model of E. coli metabolism that quantitatively accounts for observed behaviors and successfully predicts the response of E. coli to new perturbations. We reconcile these theories and clarify the origin, control and regulation of the acetate flux. We also find that, in turns, acetate regulates glucose metabolism by coordinating the expression of glycolytic and TCA genes. Acetate should not be considered a wasteful end-product since it is also a co-substrate and a global regulator of glucose metabolism in E. coli. This has broad implications for our understanding of overflow metabolism.

scholarly journals Overlapping stimulons arising in response to divergent stresses in Escherichia coli

2021 ◽  
Author(s):  
Huijing Wang ◽  
GW McElfresh ◽  
Nishantha Wijesuriya ◽  
Adam Podgorny ◽  
Andrew D Hecht ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Stress Response ◽  
Stress Responses ◽  
Differential Expression Analysis ◽  
Stringent Response ◽  
Coli Strain ◽  
Growth Media ◽  
Overflow Metabolism ◽  
Rna Seq ◽  
E Coli

Cellular responses to stress can cause a similar change in some facets of fitness even if the stresses are different. Lactose as a sole carbon source for Escherichia coli is an established example: too little causes starvation while excessive lactose import causes toxicity as a side-effect. In an E. coli strain that is robust to osmotic and ionic differences in growth media, B REL606, the rate of antibiotic-tolerant persister formation is elevated in both starvation-inducing and toxicity-inducing concentrations of lactose in comparison to less stressful intermediate concentrations. Such similarities between starvation and toxification raise the question of how much the global stress response stimulon differs between them. We hypothesized that a common stress response is conserved between the two conditions, but that a previously shown threshold driving growth rate heterogeneity in a lactose-toxifying medium would reveal that the growing fraction of cells in that medium to be missing key stress responses that curb growth. To test this, we performed RNA-seq in three representative conditions for differential expression analysis. In comparison to nominally unstressed cultures, both stress conditions showed global shifts in gene expression, with informative similarities and differences. Functional analysis of pathways, gene ontology terms, and clusters of orthogonal groups revealed signatures of overflow metabolism, membrane component shifts, and altered cytosolic and periplasmic contents in toxified cultures. Starving cultures showed an increased tendency toward stringent response-like regulatory signatures. Along with other emerging evidence, our results show multiple possible pathways to stress responses, persistence, and possibly other phenotypes. These results suggest a set of overlapping responses that drives emergence of stress-tolerant phenotypes in diverse conditions.

Novel biosynthesis of L-malate based on overflow metabolism in Escherichia coli

2019 ◽  
Vol 149 ◽  
pp. 107255 ◽  
Author(s):  
Jiangfeng Ma ◽  
Hui Qian ◽  
Tianwen Zheng ◽  
Youming Jiang ◽  
Fengxue Xin ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Overflow Metabolism

scholarly journals Overflow Metabolism in Escherichia coli during Steady-State Growth: Transcriptional Regulation and Effect of the Redox Ratio

2006 ◽  
Vol 72 (5) ◽  
pp. 3653-3661 ◽  
Author(s):  
G. N. Vemuri ◽  
E. Altman ◽  
D. P. Sangurdekar ◽  
A. B. Khodursky ◽  
M. A. Eiteman
Keyword(s):  
Escherichia Coli ◽  
Consumption Rate ◽  
Nadh Oxidase ◽  
Glucose Consumption ◽  
Tca Cycle ◽  
Overflow Metabolism ◽  
Glucose Consumption Rate ◽  
Redox Ratio ◽  
E Coli ◽  
Acetate Formation

ABSTRACT Overflow metabolism in the form of aerobic acetate excretion by Escherichia coli is an important physiological characteristic of this common industrial microorganism. Although acetate formation occurs under conditions of high glucose consumption, the genetic mechanisms that trigger this phenomenon are not clearly understood. We report on the role of the NADH/NAD ratio (redox ratio) in overflow metabolism. We modulated the redox ratio in E. coli through the expression of Streptococcus pneumoniae (water-forming) NADH oxidase. Using steady-state chemostat cultures, we demonstrated a strong correlation between acetate formation and this redox ratio. We furthermore completed genome-wide transcription analyses of a control E. coli strain and an E. coli strain overexpressing NADH oxidase. The transcription results showed that in the control strain, several genes involved in the tricarboxylic acid (TCA) cycle and respiration were repressed as the glucose consumption rate increased. Moreover, the relative repression of these genes was alleviated by expression of NADH oxidase and the resulting reduced redox ratio. Analysis of a promoter binding site upstream of the genes which correlated with redox ratio revealed a degenerate sequence with strong homology with the binding site for ArcA. Deletion of arcA resulted in acetate reduction and increased the biomass yield due to the increased capacities of the TCA cycle and respiration. Acetate formation was completely eliminated by reducing the redox ratio through expression of NADH oxidase in the arcA mutant, even at a very high glucose consumption rate. The results provide a basis for studying new regulatory mechanisms prevalent at reduced NADH/NAD ratios, as well as for designing more efficient bioprocesses.

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