Bottom-up Metabolic Reconstruction of Arabidopsis and Its Application to Determining the Metabolic Costs of Enzyme Production[W]
Bottom-up Metabolic Reconstruction of Arabidopsis and Its Application to Determining the Metabolic Costs of Enzyme Production[W]
复制标题
拟南芥自下而上的代谢重建及其在确定酶生产代谢成本中的应用[W]
作者：
Anne Arnold;Z. Nikoloski
以自下而上的方式组装了具有三种条件特异性生物量组成的拟南芥的大规模代谢模型，以估计Rubisco的酶成本。植物代谢的大规模建模提供了比较和对比不同细胞和环境情景的可能性，最终目的是确定各自植物行为背后的成分。现有的拟南芥（Arabidopsis thaliana）模型是自上而下组装的，其起点是注释的基因组，特别是代谢基因。因此，可能会出现终端代谢物和阻断反应，随后通过使用空白填充算法与物种非特异性基因结合来解决这些问题。在这里，我们提出了一个自底向上组装的大规模模型，该模型仅依赖于拟南芥特定的注释，并且只包含人工策划的反应。虽然现有的模型在很大程度上是不具体的条件，通过采用单一的生物质反应，我们提供了三种生物质组成，适用于现实和经常检查的场景：碳限制，氮限制和最佳生长条件。对比分析表明，拟南芥核心模型在碳利用效率和灵活性方面与现有网络替代方案相当。此外，该模型还用于量化光自养生长条件下氨基酸和酶从头合成的能量需求。以世界上最丰富的蛋白质Rubisco为例，我们根据ATP需求确定其合成成本。这反过来又使我们能够探索拟南芥中蛋白质合成和生长之间的权衡。总之，该模型为高通量数据（如基因表达水平）的完全物种特异性整合和硅代谢工程策略的条件特异性研究提供了坚实的基础。
A large-scale metabolic model of Arabidopsis with three condition-specific biomass compositions is assembled in a bottom-up fashion to estimate the enzyme costs of Rubisco. Large-scale modeling of plant metabolism provides the possibility to compare and contrast different cellular and environmental scenarios with the ultimate aim of identifying the components underlying the respective plant behavior. The existing models of Arabidopsis (Arabidopsis thaliana) are top-down assembled, whereby the starting point is the annotated genome, in particular, the metabolic genes. Hence, dead-end metabolites and blocked reactions can arise that are subsequently addressed by using gap-filling algorithms in combination with species-unspecific genes. Here, we present a bottom-up-assembled, large-scale model that relies solely on Arabidopsis-specific annotations and results in the inclusion of only manually curated reactions. While the existing models are largely condition unspecific by employing a single biomass reaction, we provide three biomass compositions that pertain to realistic and frequently examined scenarios: carbon-limiting, nitrogen-limiting, and optimal growth conditions. The comparative analysis indicates that the proposed Arabidopsis core model exhibits comparable efficiency in carbon utilization and flexibility to the existing network alternatives. Moreover, the model is utilized to quantify the energy demand of amino acid and enzyme de novo synthesis in photoautotrophic growth conditions. Illustrated by the case of the most abundant protein in the world, Rubisco, we determine its synthesis cost in terms of ATP requirements. This, in turn, allows us to explore the tradeoff between protein synthesis and growth in Arabidopsis. Altogether, the model provides a solid basis for completely species-specific integration of high-throughput data, such as gene expression levels, and for condition-specific investigations of in silico metabolic engineering strategies.
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影响因子：
20.3
作者：
Kalathottukaren, Manu Thomas;Abraham, Libin;Kizhakkedathu, Jayachandran N.
通讯作者：
Kizhakkedathu, Jayachandran N.
影响因子：
56.9
作者：
BACHMAIR, A;FINLEY, D;VARSHAVSKY, A
通讯作者：
VARSHAVSKY, A
什么是通量平衡分析？
影响因子：
46.9
作者：
通讯作者：
--
DOI：
10.1073/pnas.1215142110
发表时间：
2013-02-19
影响因子：
11.1
作者：
Pick, Thea R.;Braeutigam, Andrea;Weber, Andreas P. M.
通讯作者：
Weber, Andreas P. M.