AraGEM, a Genome-Scale Reconstruction of the Primary Metabolic Network in Arabidopsis

AraGEM, a Genome-Scale Reconstruction of the Primary Metabolic Network in Arabidopsis
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DOI:
10.1104/pp.109.148817
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发表时间:
2010-02-01
期刊:
影响因子:
7.4
通讯作者:
Nielsen, Lars Keld
Nielsen, Lars Keld
中科院分区:
生物学1区
文献类型:
--
作者:
Dal'Molin, Cristiana Gomes de Oliveira;Quek, Lake-Ee;Nielsen, Lars Keld

文献摘要

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基因组尺度的代谢网络模型已经成功地用于描述各种微生物以及特定哺乳动物细胞类型和细胞器的代谢。这个基于系统的框架能够探索基因敲除、基因插入和基因表达上调的全球表型效应。基于拟南芥(Arabidopsis thaliana)基因组,我们开发了一个覆盖分区植物细胞初级代谢的基因组尺度代谢网络模型(AraGEM)。AraGEM是一个全面的基于文献的基因组级代谢重建,它解释了1419个独特的开放阅读框,1748个代谢物,5253个基因-酶反应关联条目和1567个独特反应的功能,这些反应被划分为细胞质,线粒体,质体,过氧化物酶体和液泡。策化过程确定了75个基本反应,它们各自具有酶关联,而不是在京都基因和基因组百科全书或AraCyc中指定任何特定基因。随着这些反应的加入,AraGEM描述了拟南芥的功能性初级代谢。将重建的网络转化为植物代谢的计算机代谢通量模型,并通过对文献中推断的植物代谢功能的模拟进行验证。AraGEM以有效的资源利用为最优标准,预测了经典的光呼吸循环以及已知的光合和非光合植物细胞氧化还原代谢之间的关键差异。AraGEM是一个可行的硅功能分析框架,可用于探索植物代谢的新的,重要的假设。
Genome-scale metabolic network models have been successfully used to describe metabolism in a variety of microbial organisms as well as specific mammalian cell types and organelles. This systems-based framework enables the exploration of global phenotypic effects of gene knockouts, gene insertion, and up-regulation of gene expression. We have developed a genome-scale metabolic network model (AraGEM) covering primary metabolism for a compartmentalized plant cell based on the Arabidopsis (Arabidopsis thaliana) genome. AraGEM is a comprehensive literature-based, genome-scale metabolic reconstruction that accounts for the functions of 1,419 unique open reading frames, 1,748 metabolites, 5,253 gene-enzyme reaction-association entries, and 1,567 unique reactions compartmentalized into the cytoplasm, mitochondrion, plastid, peroxisome, and vacuole. The curation process identified 75 essential reactions with respective enzyme associations not assigned to any particular gene in the Kyoto Encyclopedia of Genes and Genomes or AraCyc. With the addition of these reactions, AraGEM describes a functional primary metabolism of Arabidopsis. The reconstructed network was transformed into an in silico metabolic flux model of plant metabolism and validated through the simulation of plant metabolic functions inferred from the literature. Using efficient resource utilization as the optimality criterion, AraGEM predicted the classical photorespiratory cycle as well as known key differences between redox metabolism in photosynthetic and nonphotosynthetic plant cells. AraGEM is a viable framework for in silico functional analysis and can be used to derive new, nontrivial hypotheses for exploring plant metabolism.