Computer-aided rational design of the phosphotransferase system for enhanced glucose uptake in Escherichia coli

Nishio, Yoshihiko; Usuda, Yoshihiro; Matsui, Kunihiko; Kurata, Hiroyuki

doi:10.1016/j.jbiotec.2008.07.043

Cited by 5 publications

(51 citation statements)

References 52 publications

(9 reference statements)

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“…In this study, we compare two models describing catabolite repression in E. coli by discussing some relevant issues of modelling in systems biology, model validation, dynamics and control. Nishio et al [15] described the glucose PTS, the main glucose uptake system of E. coli. The authors argued that an improved and higher uptake rate of glucose would have some benefits in biotechnological applications, as the uptake of the main carbohydrate is the key for the production of secondary metabolites or foreign proteins.…”

Section: Mathematical Models Of Catabolite Repression In E Colimentioning

confidence: 99%

“…A modular concept was used by Nishio et al [15] to define the units that describe the genetic organization of the PTS: the genes and enzymes ⁄ proteins involved are separated into four units. The contribution focuses on the extracellular glucose concentration as input into the defined units; changes in this concentration will lead to different degrees of phosphorylation of the PTS proteins EI, HPr, EIIA and EIICB.…”

Section: Phosphoenolpyruvate ⁄ Pyruvate Ratio Is the Most Important Imentioning

confidence: 99%

“…The contribution focuses on the extracellular glucose concentration as input into the defined units; changes in this concentration will lead to different degrees of phosphorylation of the PTS proteins EI, HPr, EIIA and EIICB. Although Nishio et al [15] performed some simulation studies with different concentrations of intracellular phosphoenolpyruvate and pyruvate, the concentrations were always held constant during these experiments, and no account was taken of changes in the phosphoenolpyruvate and pyruvate concentrations as a result of altered glycolytic fluxes. Neglecting this important input into the PTS restricts the changes in the degree of phosphorylation of PTS proteins to changes only in the extracellular glucose concentration (Fig.…”

Section: Phosphoenolpyruvate ⁄ Pyruvate Ratio Is the Most Important Imentioning

confidence: 99%

“…In addition, it allows the analysis of cellular processes in the case of mutations in the glucose uptake system or the PTS. Setting the concentration of phosphoenolpyruvate and pyruvate to constant values independent of the glycolytic flux, as in Nishio et al [15], means that this crucial and very important point is disregarded when trying to understand and model glucose uptake via the PTS.…”

Section: Phosphoenolpyruvate ⁄ Pyruvate Ratio Is the Most Important Imentioning

confidence: 99%

“…As the growth rate changes for the different experimental set-ups and depends on time t, the influence of the dilution term can be very prominent. During examination of the general form of the equations used by Nishio et al [15], dilution was not considered.…”

Section: Dilution Caused By Cellular Growthmentioning

confidence: 99%

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Catabolite repression in Escherichia coli– a comparison of modelling approaches

Kremling

Bettenbrock

2008

The FEBS Journal

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Research in systems biology requires experimental effort as well as theoretical attempts to elucidate the general principles of cellular dynamics and control and to help to improve molecular processes for engineering purposes or drug design. This interdisciplinary approach provides a promising method for advances in biotechnology and molecular medicine. In systems biology, quantitative experimental data and mathematical models are combined in an attempt to obtain information on the dynamics and regulatory structures of the systems. However, depending on the degree of biological knowledge and the amount of quantitative data, the models developed so far differ in their degree of granularity, starting with a simple on ⁄ off binary description of the state variables of the system and ending with fully mechanistic models. Carbohydrate uptake via the phosphoenolpyruvate-dependent phosphotransferase system (PTS) in Escherichia coli is one of the best studied biochemical networks from theoretical and experimental points of view, and has The phosphotransferase system in Escherichia coli is a transport and sensory system and, in this function, is one of the key players of catabolite repression. Mathematical modelling of signal transduction and gene expression of the enzymes involved in the transport of carbohydrates is a promising approach in biotechnology, as it offers the possibility to achieve higher production rates of desired components. In this article, the relevance of methods and approaches concerning mathematical modelling in systems biology is discussed by assessing and comparing two comprehensive mathematical models that describe catabolite repression. The focus is thereby on modular modelling with the relevant input in the central modules, the impact of quantitative model validation, the identification of control structures and the comparison of model predictions with respect to the available experimental data.Abbreviations cAMP, cyclic AMP (signalling molecule); Crp, catabolite repression protein (transcription factor); CyaA, adenylate cyclase (protein, synthesizes cAMP); dFBA, dynamic FBA (takes into account the slow dynamics of extracellular components); EI, enzyme I (protein, component of the PTS); EIIA, enzyme IIA (protein, component of the PTS, 'output' of the system as it activates the synthesis of cAMP); EIIBC (PtsG), enzyme IIBC (main membrane standing transport protein for glucose uptake); FBA, flux balance analysis (tool to determine the flux distribution in cellular networks, requires steady-state conditions); HPr, histidine-containing protein (component of the PTS); LacZ, protein of the lactose degradation pathway (b-galactodidase); Mlc, repressor protein (inhibits the synthesis of EIIBC if glucose is not present in the medium); o.d.e., ordinary differential equation (basic structure of a mathematical model, it describes the temporal changes of a component in the network, must be solved numerically); PTS, phosphotransferase system (uptake and sensory system in many bacteria, consists of several pr...

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Section: Mathematical Models Of Catabolite Repression In E Colimentioning

confidence: 99%

Section: Phosphoenolpyruvate ⁄ Pyruvate Ratio Is the Most Important Imentioning

confidence: 99%

Section: Phosphoenolpyruvate ⁄ Pyruvate Ratio Is the Most Important Imentioning

confidence: 99%

Section: Phosphoenolpyruvate ⁄ Pyruvate Ratio Is the Most Important Imentioning

confidence: 99%

Section: Dilution Caused By Cellular Growthmentioning

confidence: 99%

See 3 more Smart Citations

Catabolite repression in Escherichia coli– a comparison of modelling approaches

Kremling

Bettenbrock

2008

The FEBS Journal

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Chip-seq and gene expression data for the identification of functional sub-pathways: a proof of concept in lung cancer

Atsalaki

Koumakis

Potamias

et al. 2020

Preprint

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High-throughput technologies, such as chromatin immunoprecipitation (ChIP) with massively parallel sequencing (ChIP-seq) have enabled cost and time efficient generation of immense amount of genome data. The advent of advanced sequencing techniques allowed biologists and bioinformaticians to investigate biological aspects of cell function and understand or reveal unexplored disease etiologies. Systems biology attempts to formulate the molecular mechanisms in mathematical models and one of the most important areas is the gene regulatory networks (GRNs), a collection of DNA segments that somehow interact with each other. GRNs incorporate valuable information about molecular targets that can be corellated to specific phenotype.In our study we highlight the need to develop new explorative tools and approaches for the integration of different types of -omics data such as ChIP-seq and GRNs using pathway analysis methodologies. We present an integrative approach for ChIP-seq and gene expression data on GRNs. Using public microarray expression samples for lung cancer and healthy subjects along with the KEGG human gene regulatory networks, we identified ways to disrupt functional sub-pathways on lung cancer with the aid of CTCF ChIPseq data, as a proof of concept.We expect that such a systems biology pipeline could assist researchers to identify corellations and causality of transcription factors over functional or disrupted biological subpathways.

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Current status and future perspectives of kinetic modeling for the cell metabolism with incorporation of the metabolic regulation mechanism

Matsuoka

Shimizu

2015

Bioresour. Bioprocess.

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It becomes more and more important to develop appropriate models for the efficient design of the cell factory for microbial biofuels and biochemical productions, since the appropriate model can predict the effect of culture environment and/or the specific pathway genes knockout on the growth characteristics. Among various modeling approaches, kinetic modeling is promising in the sense of realizing the essential feature of metabolic regulation. A brief overview is given for the current status of the kinetic modeling of the cell metabolism from the point of view of metabolic regulation focusing on Escherichia coli (but not limited to E. coli). For the proper modeling, it is important to realize the systems behavior by integrating different levels of information to understand and unravel the underlying principles of the living organisms, namely, it is important to properly understand how the environmental stimuli are detected by the cell, how those are transduced, and how the cell metabolism is regulated, and to express these into the model. In particular, it is important to incorporate the enzymatic regulations of Pyk, Pfk, and Ppc by fructose-1,6-bisphosphate (FBP), phosphoenol pyruvate (PEP), and acetyl-coenzyme A (AcCoA) to realize the flux-sensing and homeostatic behavior. The proper modeling for phosphotransferase system (PTS) and the transcriptional regulation by cAMP-Crp and Cra is also important to simulate the main metabolism in relation to catabolite regulation. The coordinated regulation between catabolic and anabolic (nitrogen source-assimilation) metabolisms may be simulated by the behavior of keto acid such as α-ketoglutarate (αKG). The metabolism under micro-aerobic conditions may be made by incorporating the global regulators such as ArcA/B and Fnr. It is quite important to develop quantitative kinetic models, which incorporate enzyme level and gene level regulations from the biological science and metabolic engineering points of view.

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Computer-aided rational design of the phosphotransferase system for enhanced glucose uptake in Escherichia coli

Cited by 5 publications

References 52 publications

Catabolite repression in Escherichia coli– a comparison of modelling approaches

Catabolite repression in Escherichia coli– a comparison of modelling approaches

Chip-seq and gene expression data for the identification of functional sub-pathways: a proof of concept in lung cancer

Current status and future perspectives of kinetic modeling for the cell metabolism with incorporation of the metabolic regulation mechanism

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