Essentiality and damage in metabolic networks

Lemke, Ney; Herédia, Fabiana; Barcellos, Cláudia K.; Reis, Adriana Neves dos; Mombach, José C. M.

doi:10.1093/bioinformatics/btg386

Cited by 76 publications

(60 citation statements)

References 17 publications

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“…The results (figure 3) indicate that most mutations (76%) in metabolic enzymes encoded in the minimal genome prevent the synthesis of at least one compound. This is in sharp contrast to what was found for the E. coli metabolic network, in which the vast majority of the mutations produced no network damage (Lemke et al 2004). Thus, it appears that a lower redundancy in enzyme activities in the minimal genome, coupled with a lack of alternative pathways for the synthesis of most compounds, compromises the robustness of the emerging metabolism in terms of the metabolic damage Mushegian & Koonin (1996) proposed MG264 (dephospho-CoA kinase, EC 2.7.1.24) and MG268 (conserved hypothetical protein) as candidates for the role of NDK.…”

Section: Resultscontrasting

confidence: 98%

“…We must keep in mind, however, that retaining the global topological properties of a network does not necessarily mean that the resulting mutated networks are viable. Recently, Lemke et al (2004) have introduced a new quantitative criterion to evaluate the deleterious effect of the removal of an enzyme from a metabolic network.…”

Section: Resultsmentioning

confidence: 99%

“…To ascertain whether the proposed minimal metabolism is also robust regarding this new parameter, we conducted the same experiment using the algorithm described by Lemke et al (2004). The results (figure 3) indicate that most mutations (76%) in metabolic enzymes encoded in the minimal genome prevent the synthesis of at least one compound.…”

Section: Resultsmentioning

confidence: 99%

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Structural analyses of a hypothetical minimal metabolism

Gabaldón

Peretó

Montero

et al. 2007

Phil. Trans. R. Soc. B

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By integrating data from comparative genomics and large-scale deletion studies, we previously proposed a minimal gene set comprising 206 protein-coding genes. To evaluate the consistency of the metabolism encoded by such a minimal genome, we have carried out a series of computational analyses. Firstly, the topology of the minimal metabolism was compared with that of the reconstructed networks from natural bacterial genomes. Secondly, the robustness of the metabolic network was evaluated by simulated mutagenesis and, finally, the stoichiometric consistency was assessed by automatically deriving the steadystate solutions from the reaction set. The results indicated that the proposed minimal metabolism presents stoichiometric consistency and that it is organized as a complex power-law network with topological parameters falling within the expected range for a natural metabolism of its size. The robustness analyses revealed that most random mutations do not alter the topology of the network significantly, but do cause significant damage by preventing the synthesis of several compounds or compromising the stoichiometric consistency of the metabolism. The implications that these results have on the origins of metabolic complexity and the theoretical design of an artificial minimal cell are discussed.

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Section: Resultscontrasting

confidence: 98%

Section: Resultsmentioning

confidence: 99%

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Structural analyses of a hypothetical minimal metabolism

Gabaldón

Peretó

Montero

et al. 2007

Phil. Trans. R. Soc. B

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“…We treat reversible reactions as two separate reactions. To calculate the damage, we select an enzyme and delete all reactions it catalyzes; the number of deleted metabolites is defined as d. For more details see reference Lemke et al (2004). The method was motivated by experiments of systematic mutagenesis where the importance of each gene is tested for the survival of an organism.…”

Section: Short Communicationmentioning

confidence: 99%

Using the FORESTS and KEGG databases to investigate the metabolic network of Eucalyptus

et al. 2005

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In this work we apply a bioinformatics approach to determine the most important enzymes of the metabolic network of Eucalyptus to determine the coverage of the genome in the FORESTS library. We conclude that the library does not cover completely the metabolism of the organism. However, some important pathways could be analyzed, especially the lignin synthesis. We found that four of the most important enzymes predicted are involved in this pathway.Key words: Eucalyptus, metabolism. The genome sequences of several organisms are available (Kanehisa and Goto, 2000) currently and the extraction of relevant physiological information from these data is a major challenge. The metabolic networks reconstructed from the annotated genomes provide an abundance of information for exploration with bioinformatics (Karp et al., 1999). In this article we apply a recently developed graph analysis of metabolism that predicts important enzymes of the metabolic network of Eucalyptus. Data were obtained from the non-public database of the Eucalyptus Genome Sequencing Project Consortium (FORESTS, https://forests.esalq.usp.br/) that contains approximately 100,000 expressed sequence tags (ESTs) of this plant.Cellular metabolism is a complex network of biochemical reactions catalyzed by specialized proteins called enzymes. The reactions are organized in modules called metabolic maps with specific catabolic or anabolic functions. The complete set of metabolic maps forms the metabolic network.An exponentially growing number of organisms have sequenced genomes (Devos and Valencia, 2001), and assuming that the annotated proteins are expressed, we can reconstruct the metabolic network of the organism (Karp et al., 1999).The investigation of the influence of enzymes on the network is a critical issue for the bioengineering and pharmaceutical industry since they can be targets for drugs (Karp et al., 1999) or they can be genetically engineered to change the metabolic output of specific metabolites (Edwards and Palsson, 1997). Our approach investigates the static structure of the components of the network to infer causal and physiological relationships. In a previous work we applied our method to Escherichia coli, whose metabolism has been studied in depth, and found a strong correlation between the damage an enzyme causes to the network and its essentiality , thus showing the predictive power the method has for determining important enzymes. In this work we apply this method to the genome of Eucalyptus that is an important commercial source of wood and cellulose. In particular, there is a great deal of interest in the bioengineering of plants involving the metabolic pathways of cellulose and lignin to generate genetically modified organisms with enhanced production of cellulose and decreased production of lignin.In our method we have introduced a new quantitative criterion for enzyme importance: the damage its removal causes to the metabolic network . In the absence of complete information about kinetic parameters and the influence of t...

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“…Thus the prediction of function from the metabolic networks has become an essential step in the post-genomic era [4,[7][8][9][10][11] . However, before it is possible to investigate the potential relationship between structure and functionality of a metabolic network, it is necessary to study how the metabolic networks are actually constructed.…”

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confidence: 99%

Bow-tie topological features of metabolic networks and the functional significance

Zhao

Lin

et al. 2007

Chin. Sci. Bull.

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Exploring the structural topology of genome-based large-scale metabolic network is essential for investigating possible relations between structure and functionality. Visualization would be helpful for obtaining immediate information about structural organization. In this work, metabolic networks of 75 organisms were investigated from a topological point of view. A spread bow-tie model was proposed to give a clear visualization of the bow-tie structure for metabolic networks. The revealed topological pattern helps to design more efficient algorithm specifically for metabolic networks. This coarse-grained graph also visualizes the vulnerable connections in the network, and thus could have important implication for disease studies and drug target identifications. In addition, analysis on the reciprocal links and main cores in the GSC part of bow-tie also reveals that the bow-tie structure of metabolic networks has its own intrinsic and significant features which are significantly different from those of random networks.Keywords: bioinformatics; metabolic network; bow-tie; random network.As the results of various genome projects, the genome sequences of many organisms are available and the organism specific metabolic networks can be faithfully reconstructed from genome information [1][2][3][4][5][6] . Thus the prediction of function from the metabolic networks has become an essential step in the post-genomic era [4,[7][8][9][10][11] . However, before it is possible to investigate the potential relationship between structure and functionality of a metabolic network, it is necessary to study how the metabolic networks are actually constructed.In recent years there has been a strongly increasing passion in investigating the intricate structures of link topologies in metabolic networks [12][13][14][15][16][17][18][19][20][21] . Many researchers have applied methods from graph theory to treat the metabolic networks as a directed graph consisting of nodes denoting metabolites connected by directed arcs representing reactions. An important finding is that metabolic networks, as well as other real-world complex networks, have topologies that differ markedly from those found in simple randomly connected networks [22] , which suggests that their non-random structures could imply significant organizing principles of metabolic networks.From the computational analysis of genome-based metabolic networks of 65 organisms, Ma and Zeng discovered that the global metabolic network is organized in the form of a bow-tie [15] . On the other hand, from the view of material flows and information flows in the metabolic system, Csete and Doyle described metabolism as several nested bow-ties [23] . It was pointed out that bow-tie architectures facilitate robust biologic function, and based on their design, also have

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Essentiality and damage in metabolic networks

Cited by 76 publications

References 17 publications

Structural analyses of a hypothetical minimal metabolism

Structural analyses of a hypothetical minimal metabolism

Using the FORESTS and KEGG databases to investigate the metabolic network of Eucalyptus

Bow-tie topological features of metabolic networks and the functional significance

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