Robustness in Escherichia coli Glutamate and Glutamine Synthesis Studied by a Kinetic Model

Lodeiro, Aníbal Roberto; Melgarejo, Augusto A.

doi:10.1007/s10867-008-9109-9

Cited by 7 publications

(10 citation statements)

References 19 publications

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“…The presence/absence of GS regulation and of GOGAT was analyzed. GS regulation provided a greater robustness of the fluxes against perturbations of enzyme or ammonium concentrations, in particular when the ammonium supply fluctuated (569). A flux balance model for nitrogen metabolism was developed (570) and verified by experiments carried out for the wild-type and GDH and GOGAT knockout strains (135,567).…”

Section: Estimating Fluxes In Vivomentioning

confidence: 99%

Nitrogen Assimilation in Escherichia coli: Putting Molecular Data into a Systems Perspective

Heeswijk¹,

Westerhoff

Boogerd³

2013

Microbiol Mol Biol Rev

232

246

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SUMMARY We present a comprehensive overview of the hierarchical network of intracellular processes revolving around central nitrogen metabolism in Escherichia coli . The hierarchy intertwines transport, metabolism, signaling leading to posttranslational modification, and transcription. The protein components of the network include an ammonium transporter (AmtB), a glutamine transporter (GlnHPQ), two ammonium assimilation pathways (glutamine synthetase [GS]-glutamate synthase [glutamine 2-oxoglutarate amidotransferase {GOGAT}] and glutamate dehydrogenase [GDH]), the two bifunctional enzymes adenylyl transferase/adenylyl-removing enzyme (ATase) and uridylyl transferase/uridylyl-removing enzyme (UTase), the two trimeric signal transduction proteins (GlnB and GlnK), the two-component regulatory system composed of the histidine protein kinase nitrogen regulator II (NRII) and the response nitrogen regulator I (NRI), three global transcriptional regulators called nitrogen assimilation control (Nac) protein, leucine-responsive regulatory protein (Lrp), and cyclic AMP (cAMP) receptor protein (Crp), the glutaminases, and the nitrogen-phosphotransferase system. First, the structural and molecular knowledge on these proteins is reviewed. Thereafter, the activities of the components as they engage together in transport, metabolism, signal transduction, and transcription and their regulation are discussed. Next, old and new molecular data and physiological data are put into a common perspective on integral cellular functioning, especially with the aim of resolving counterintuitive or paradoxical processes featured in nitrogen assimilation. Finally, we articulate what still remains to be discovered and what general lessons can be learned from the vast amounts of data that are available now.

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Section: Estimating Fluxes In Vivomentioning

confidence: 99%

Nitrogen Assimilation in Escherichia coli: Putting Molecular Data into a Systems Perspective

Heeswijk¹,

Westerhoff

Boogerd³

2013

Microbiol Mol Biol Rev

232

246

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show abstract

“…While the whole system can be qualitatively understood on the basis of the regulatory connections (Fig. 1A), mathematical approaches are needed to allow us to quantitatively understand and model how the system responds to different nitrogen levels (Bruggeman et al , 2005; Yuan et al , 2009; Ma et al , 2009; Okano et al , 2010; Hart et al , 2011; Lodeiro & Melgarejo, 2008). Such models provide a mechanistic and testable description of the dynamics at the level of populations of cells.…”

Section: Introductionmentioning

confidence: 99%

Analog nitrogen sensing inEscherichia colienables high fidelity information processing

Komorowski

Schumacher

Behrends

et al. 2015

Preprint

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The molecular reaction networks that coordinate the response of an organism to changing environmental conditions are central for survival and reproduction. Escherchia coli employs an accurate and flexible signalling system that is capable of processing ambient nitrogen availability rapidly and with high accuracy. Carefully orchestrated post-translational modifications of PII and the glutamine synthetase allow E. coli to trace nitrogen availability in a continuous, decidedly non-digital fashion. We measure the dynamic proteomic and metabolomic responses to trace the analog computations, and use an information theoretical framework to characterize the information capacity of E. coli’s nitrogen sensing network: we find that this system can transmit up to 9bits of information about the nitrogen state. This allows cells to respond rapidly and accurately even to small differences in metabolite concentrations.

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“…Later work moved onto establishing ordinary differential equation (ODE) models and simulating the systemic dynamics [12], [13], [14], [15], [16]. More recently, Yuan and coworkers combined their ODE model with massive experimental data of metabolomics to investigate the hypothesis of active-site competition on GOGAT [17].…”

Section: Introductionmentioning

confidence: 99%

Flux Balance Analysis of Ammonia Assimilation Network in E. coli Predicts Preferred Regulation Point

et al. 2011

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Nitrogen assimilation is a critical biological process for the synthesis of biomolecules in Escherichia coli. The central ammonium assimilation network in E. coli converts carbon skeleton α-ketoglutarate and ammonium into glutamate and glutamine, which further serve as nitrogen donors for nitrogen metabolism in the cell. This reaction network involves three enzymes: glutamate dehydrogenase (GDH), glutamine synthetase (GS) and glutamate synthase (GOGAT). In minimal media, E. coli tries to maintain an optimal growth rate by regulating the activity of the enzymes to match the availability of the external ammonia. The molecular mechanism and the strategy of the regulation in this network have been the research topics for many investigators. In this paper, we develop a flux balance model for the nitrogen metabolism, taking into account of the cellular composition and biosynthetic requirements for nitrogen. The model agrees well with known experimental results. Specifically, it reproduces all the 15N isotope labeling experiments in the wild type and the two mutant (ΔGDH and ΔGOGAT) strains of E. coli. Furthermore, the predicted catalytic activities of GDH, GS and GOGAT in different ammonium concentrations and growth rates for the wild type, ΔGDH and ΔGOGAT strains agree well with the enzyme concentrations obtained from western blots. Based on this flux balance model, we show that GS is the preferred regulation point among the three enzymes in the nitrogen assimilation network. Our analysis reveals the pattern of regulation in this central and highly regulated network, thus providing insights into the regulation strategy adopted by the bacteria. Our model and methods may also be useful in future investigations in this and other networks.

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Robustness in Escherichia coli Glutamate and Glutamine Synthesis Studied by a Kinetic Model

Cited by 7 publications

References 19 publications

Nitrogen Assimilation in Escherichia coli: Putting Molecular Data into a Systems Perspective

Nitrogen Assimilation in Escherichia coli: Putting Molecular Data into a Systems Perspective

Analog nitrogen sensing inEscherichia colienables high fidelity information processing

Flux Balance Analysis of Ammonia Assimilation Network in E. coli Predicts Preferred Regulation Point

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