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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Reconstruction of Arabidopsis metabolic network models accounting for subcellular compartmentalization and tissue-specificity
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Reconstruction of Arabidopsis metabolic network models accounting for subcellular compartmentalization and tissue-specificity

机译：重构拟南芥代谢网络模型，考虑亚细胞区室化和组织特异性

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摘要

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-compli-. ant and are available upon request.
机译：植物代谢工程通常用于功能食品的生产和质量性状的改善。但是，迄今为止，基于计算模型的方法仅在该重要工作中很少使用，这与它们在微生物代谢工程中的显著成功形成鲜明对比。在这项研究中，我们提出了一个在基因组规模上重建拟南芥完全分隔的组织特异性模型的计算管道。这种重建包括自动提取拟南芥中用于一级代谢和二级代谢的已知生化反应，自动填充缺口，以及实施确定亚细胞定位和酶组织分配的方法。重建的组织模型适用于基于约束的建模分析，并且在以前的模型重建上有很大的扩展。一组计算验证（即交叉验证测试，已知代谢功能的模拟）和实验验证（与各种隔室和组织下的实验代谢组学数据集进行比较）有力地证明了模型的预测能力。衍生模型的实用性在代谢工程种子菌株中测得的通量的预测和预期增加维生素E含量（对人类健康的重要营养素）的基因操作设计中得到了证明。总体而言，重建的组织模型有望为植物代谢工程基于计算的合理设计奠定基础。重建的分隔拟南芥组织模型是MIRIAM-compli-。蚂蚁，可应要求提供。

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

  • 作者单位

    Department of Plant Sciences, Weizmann Institute of Science, Rehovot 76100, Israel;

    Department of Plant Sciences, Weizmann Institute of Science, Rehovot 76100, Israel;

    Department of Plant Sciences, Weizmann Institute of Science, Rehovot 76100, Israel;

    School of Computer Science, Tel-Aviv University, Tel-Aviv 69978, Israel,School of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel;

    Department of Plant Sciences, Weizmann Institute of Science, Rehovot 76100, Israel;

    Department of Computer Science, Technion-lsrael Institute of Technology, Haifa 32000, Israel;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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