A genome-scale metabolic model of Arabidopsis and some of its properties

Abstract

We describe the construction and analysis of a genome-scale metabolic model of Arabidopsis (Arabidopsis thaliana) primarily derived from the annotations in the Aracyc database. We used techniques based on linear programming to demonstrate the following: (1) that the model is capable of producing biomass components (amino acids, nucleotides, lipid, starch, and cellulose) in the proportions observed experimentally in a heterotrophic suspension culture; (2) that approximately only 15% of the available reactions are needed for this purpose and that the size of this network is comparable to estimates of minimal network size for other organisms; (3) that reactions may be grouped according to the changes in flux resulting from a hypothetical stimulus (in this case demand for ATP) and that this allows the identification of potential metabolic modules; and (4) that total ATP demand for growth and maintenance can be inferred and that this is consistent with previous estimates in prokaryotes and yeast.

Figure 1.

The correlation tree of reaction fluxes in the LP model. Uppercase reaction names are Biocyc identifiers, which in some cases have been modified to make them compatible with the tree-drawing software. Reactions with the suffix “tx” represent transporters, NADOxid is the generic NADH oxidase, and all other reactions are from the mitochondrial component of the model. The scale bar represents cos⁻¹ (r) = 0.5 (equivalent to r ∼ 0.9). Subtrees are colored such that reactions with cos⁻¹ (r) ≤ 0.5 share a common color. These can be identified as (predominantly) belonging to common areas of metabolism as follows: blue, reversible oxidative pentose phosphate pathway/Calvin cycle reactions; red, glycolysis and mitochondrial reactions; green, oxidative pentose phosphate pathway and CO₂ fixation.

Figure 2.

The network composed of reactions exhibiting variable flux in response to changing ATP demand (see also Figs. 1 and 3). Colors correspond to the description in Figure 1; reactions shown with broken lines indicate those that at some level of ATP demand carry no flux (see Fig. 3). The reactions shown in black are also included, although their fluxes do not respond to changing ATP demand (in these solutions); they form a single connected block whose start and end points are in the block of variable reactions. The purpose of this diagram is to illustrate relationships between the reactions of primary metabolism, and to this end a number of simplifications have been made: metabolite names are the common abbreviations, not Biocyc identifiers; the transhydrogenase reaction at the top of the figure is composed of the NAD and NADP variants of icosanoyl-CoA synthase (EC 2.3.1.119) operating in opposed directions (see “Discussion”); the oxidative limb of the oxidative pentose phosphate pathway is shown as a single lumped reaction; and CO₂, oxygen, currency metabolites, the electron transport chain, and oxidative phosphorylation are omitted. Additional fixed outputs from the system are not shown (see “Discussion”).

Figure 3.

Responses of reaction fluxes in the model to varying ATP demand. Reactions are colored as previously, and dotted lines indicate reactions that at some point carry zero flux. The black impulses represent points at which one or more reactions become active or inactive. The size of the impulse is proportional to the number of reactions becoming (in)active; the positive impulse shows reactions becoming active, and the negative impulse represents reactions becoming inactive. Flux units are mol L⁻¹ h⁻¹.

Figure 4.

Response of P/O ratio of the LP solutions of the whole model to larger changes in ATP demand (mol L⁻¹ h⁻¹). [See online article for color version of this figure.]