Economics of membrane occupancy and respiro‐fermentation

Zhuang, Kai; Vemuri, Goutham N.; Mahadevan, Radhakrishnan

doi:10.1038/msb.2011.34

Cited by 174 publications

(177 citation statements)

References 43 publications

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“…Overflow has also been proposed to represent a trade-off between energy and biomass yield and the biosynthetic costs of respiration that occur during fast growth 31 . In addition, competition for membrane space between substrate uptake and respiration has also been proposed to be a constraint leading to carbon wasting 32 . Our results suggest that the GLPK and RPOC strains may preferentially use overflow/fermentation and respiration, respectively, while the DKI has optimized the balance between these processes and biomass yield to achieve a maximum growth rate.…”

Section: Resultsmentioning

confidence: 99%

Global metabolic network reorganization by adaptive mutations allows fast growth of Escherichia coli on glycerol

et al. 2014

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Comparative whole-genome sequencing enables the identification of specific mutations during adaptation of bacteria to new environments and allelic replacement can establish their causality. However, the mechanisms of action are hard to decipher and little has been achieved for epistatic mutations, especially at the metabolic level. Here we show that a strain of Escherichia coli carrying mutations in the rpoC and glpK genes, derived from adaptation in glycerol, uses two distinct metabolic strategies to gain growth advantage. A 27-bp deletion in the rpoC gene first increases metabolic efficiency. Then, a point mutation in the glpK gene promotes growth by improving glycerol utilization but results in increased carbon wasting as overflow metabolism. In a strain carrying both mutations, these contrasting carbon/energy saving and wasting mechanisms work together to give an 89% increase in growth rate. This study provides insight into metabolic reprogramming during adaptive laboratory evolution for fast cellular growth.

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Section: Resultsmentioning

confidence: 99%

Global metabolic network reorganization by adaptive mutations allows fast growth of Escherichia coli on glycerol

et al. 2014

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“…Is this tradeoff constant, or does it vary greatly between organisms and conditions? More sharply, how does additional protein production affect cell growth (16,(33)(34)(35), and how does metabolism evolve to cope with high protein cost (17,34)? Many researchers have begun to address these questions, but they are by no means resolved.…”

Section: Discussionmentioning

confidence: 99%

Glycolytic strategy as a tradeoff between energy yield and protein cost

Flamholz

Noor

Bar‐Even

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

450

499

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Contrary to the textbook portrayal of glycolysis as a single pathway conserved across all domains of life, not all sugar-consuming organisms use the canonical Embden-Meyerhoff-Parnass (EMP) glycolytic pathway. Prokaryotic glucose metabolism is particularly diverse, including several alternative glycolytic pathways, the most common of which is the Entner-Doudoroff (ED) pathway. The prevalence of the ED pathway is puzzling as it produces only one ATP per glucose-half as much as the EMP pathway. We argue that the diversity of prokaryotic glucose metabolism may reflect a tradeoff between a pathway's energy (ATP) yield and the amount of enzymatic protein required to catalyze pathway flux. We introduce methods for analyzing pathways in terms of thermodynamics and kinetics and show that the ED pathway is expected to require several-fold less enzymatic protein to achieve the same glucose conversion rate as the EMP pathway. Through genomic analysis, we further show that prokaryotes use different glycolytic pathways depending on their energy supply. Specifically, energy-deprived anaerobes overwhelmingly rely upon the higher ATP yield of the EMP pathway, whereas the ED pathway is common among facultative anaerobes and even more common among aerobes. In addition to demonstrating how protein costs can explain the use of alternative metabolic strategies, this study illustrates a direct connection between an organism's environment and the thermodynamic and biochemical properties of the metabolic pathways it employs.evolution | enzyme cost G lycolysis is the process by which glucose is broken down anaerobically into incompletely oxidized compounds like pyruvate, a process which is usually coupled to the synthesis of ATP. Although the Embden-Meyerhof-Parnas pathway (EMP, often simply "glycolysis") is the nearly ubiquitous glycolytic route among eukaryotes (1, 2), it is not the only game in town. Prokaryotes display impressive diversity in glucose metabolism (2, 3) and natural glycolytic alternatives like the Entner-Doudoroff (ED), and phosphoketolase pathways attest to the fact that there are multiple biologically feasible routes for glucose metabolism (2, 4-8). Natural glycolytic pathways vary in their reaction sequence and in how much ATP they produce per glucose metabolized, ranging from zero to three ATP molecules in most cases (7).The EMP and ED pathways ( Fig. 1 A and B and Fig. S1) are the most common bacterial glycolytic pathways (2, 4, 9), and their general schemes are quite similar: glucose is phosphorylated and then cleaved into two three-carbon units, which are further metabolized to produce ATP (4). In some organisms, these pathways differ slightly in the specific redox cofactors they use (e.g., NAD + vs. NADP + ; Fig. 1B, Fig. S2, and Table S1), but here we focus on the prominent difference in ATP yield. If we take lactate as a representative final product, these two pathways have the same net reaction:and differ primarily in n, the number of ATP produced, and the specific intermediate reaction steps (Fig. 1B, SI T...

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“…This probably leads to higher acetate accumulation in wild-type cells, as illustrated in Fig. 6B [47,48]. Production of acetate wastes carbon that might otherwise be directed towards protein synthesis through TCA intermediates.…”

Section: Detailed Analysis Of the Whole Cell Proteomementioning

confidence: 98%

Deciphering the interactions between the Bacillus cereus linear plasmid, pBClin15, and its host by high-throughput comparative proteomics

Madeira

Omer

Alpha-Bazin

et al. 2016

Journal of Proteomics

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Bacteria belonging to the Bacillus cereus group include B. cereus, a notorious food borne pathogen which causes gastroenteritis. The B. cereus type, strain ATCC 14579, harbors a linear plasmid, pBClin15, which displays cryptic prophage behavior. Here, we present data supporting the idea that pBClin15 may have a much greater role in B. cereus metabolism that has hitherto been suspected. Specifically, our comparative proteomic analyses reveal that pBClin15 manages B. cereus central metabolism to optimize energy and carbon utilization through the repression of several chromosome-encoded phage proteins. These results suggest that pBClin15 provides benefit to the host for surviving adverse environmental conditions.

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Economics of membrane occupancy and respiro‐fermentation

Abstract: The authors propose that prokaryotic metabolism is fundamentally constrained by the cytoplasmic membrane surface area available for protein expression, and show that this constraint can explain previously puzzling physiological phenomena, including respiro-fermentation.

Cited by 174 publications

References 43 publications

Global metabolic network reorganization by adaptive mutations allows fast growth of Escherichia coli on glycerol

Global metabolic network reorganization by adaptive mutations allows fast growth of Escherichia coli on glycerol

Glycolytic strategy as a tradeoff between energy yield and protein cost

Deciphering the interactions between the Bacillus cereus linear plasmid, pBClin15, and its host by high-throughput comparative proteomics

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