Structural analyses of a hypothetical minimal metabolism - PubMed (original) (raw)

Structural analyses of a hypothetical minimal metabolism

Toni Gabaldón et al. Philos Trans R Soc Lond B Biol Sci. 2007.

Abstract

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 steady-state 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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Figures

Figure 1

Figure 1

A simplified overview of the metabolic network implemented by a hypothetical minimal genome of 208 protein-coding genes derived by an integrated approach (modified from Gil et al. 2004). Names of substrates freely available for the hypothetical minimal cell are represented inside a frame. Two sink metabolites are labelled in grey. Coenzyme metabolism (except the folate metabolism linked to TTP biosynthesis) is shown in the inset and was not considered in the stoichiometric analysis. Wider arrows in the glycolytic pathway indicate the two steps where ATP is synthesized by substrate-level phosphorylation.

Figure 2

Figure 2

Effect of network size on the deviation of the clustering coefficient from the expected random scenario.

Figure 3

Figure 3

Network damage analysis for the minimal metabolic network. Frequency of deletions causing a given network damage (d), measured as the number of metabolites whose synthesis is prevented by that mutation.

Figure 4

Figure 4

Elementary flux modes (EFM) as a function of the ES. v i Represents denormalized rate of the subset i at every EFM. The input (Ji) and output (Jo) fluxes involved in each ES are also indicated.

Figure 5

Figure 5

The new ES emerging as a consequence of deleting the NDK5 reaction. See table 2 for abbreviations.

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