Dynamic resource allocation drives growth under nitrogen starvation in eukaryotes
Dynamic resource allocation drives growth under nitrogen starvation in eukaryotes
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DOI：
10.1038/s41540-020-0135-y
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发表时间：
2020-05
影响因子：
4
通讯作者：
Juan D. Tibocha-Bonilla;Manish Kumar;Anne Richelle;R. Godoy-Silva;K. Zengler;C. Zuñiga
中科院分区：
文献类型：
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作者：
Juan D. Tibocha-Bonilla;Manish Kumar;Anne Richelle;R. Godoy-Silva;K. Zengler;C. Zuñiga
细胞可以感知其细胞外环境的变化，并随后适应其生物质组成。营养物丰度定义了细胞产生生物质组分的能力。在营养有限的条件下，资源分配急剧转向富含碳的分子。在这里，我们使用动态的生物质组成数据来预测生长和反应通量分布的变化，使用可用的基因组规模的代谢模型的五个真核生物（三个异养和两个光养生物）。我们确定了代谢通量的时间分布，表明响应氮耗竭的途径和细胞器功能的长期趋势。令人惊讶的是，我们对模型灵敏度和生物合成成本的计算表明，生物质代谢物的自由能是生物合成成本的主要驱动因素，而不是分子量，从而解释了精氨酸和组氨酸的高成本。我们展示了代谢模型如何准确预测在生长过程中应对压力的交织机制的复杂性。
Cells can sense changes in their extracellular environment and subsequently adapt their biomass composition. Nutrient abundance defines the capability of the cell to produce biomass components. Under nutrient-limited conditions, resource allocation dramatically shifts to carbon-rich molecules. Here, we used dynamic biomass composition data to predict changes in growth and reaction flux distributions using the available genome-scale metabolic models of five eukaryotic organisms (three heterotrophs and two phototrophs). We identified temporal profiles of metabolic fluxes that indicate long-term trends in pathway and organelle function in response to nitrogen depletion. Surprisingly, our calculations of model sensitivity and biosynthetic cost showed that free energy of biomass metabolites is the main driver of biosynthetic cost and not molecular weight, thus explaining the high costs of arginine and histidine. We demonstrated how metabolic models can accurately predict the complexity of interwoven mechanisms in response to stress over the course of growth.