Reconstruction of Arabidopsis metabolic network models accounting for subcellular compartmentalization and tissue-specificity

Shira Mintz-Oron, Sagit Meir, Sergey Malitsky, Eytan Ruppin, Asaph Aharoni, Tomer Shlomi

Research output: Contribution to journalArticlepeer-review

Abstract

Plant metabolic engineering is commonly used in the production of functional foods and quality trait improvement. However, to date, computational model-based approaches have only been scarcely used in this important endeavor, in marked contrast to their prominent success in microbial metabolic engineering. In this study we present a computational pipeline for the reconstruction of fully compartmentalized tissue-specific models of Arabidopsis thaliana on a genome scale. This reconstruction involves automatic extraction of known biochemical reactions in Arabidopsis for both primary and secondary metabolism, automatic gap-filling, and the implementation of methods for determining subcellular localization and tissue assignment of enzymes. The reconstructed tissue models are amenable for constraint-based modeling analysis, and significantly extend upon previous model reconstructions. A set of computational validations (i.e., cross-validation tests, simulations of known metabolic functionalities) and experimental validations (comparison with experimental metabolomics datasets under various compartments and tissues) strongly testify to the predictive ability of the models. The utility of the derived models was demonstrated in the prediction of measured fluxes in metabolically engineered seed strains and the design of genetic manipulations that are expected to increase vitamin E content, a significant nutrient for human health. Overall, the reconstructed tissue models are expected to lay down the foundations for computational-based rational design of plant metabolic engineering. The reconstructed compartmentalized Arabidopsis tissue models are MIRIAM-compliant and are available upon request.

Original languageEnglish
Pages (from-to)339-344
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number1
DOIs
StatePublished - 3 Jan 2012

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