Department of Plant Sciences, University of Oxford, South Parks Road, Oxford, OX1 3RB, UK.
Plant J. 2013 Sep;75(6):1050-61. doi: 10.1111/tpj.12252. Epub 2013 Aug 6.
Flux balance models of metabolism generally utilize synthesis of biomass as the main determinant of intracellular fluxes. However, the biomass constraint alone is not sufficient to predict realistic fluxes in central heterotrophic metabolism of plant cells because of the major demand on the energy budget due to transport costs and cell maintenance. This major limitation can be addressed by incorporating transport steps into the metabolic model and by implementing a procedure that uses Pareto optimality analysis to explore the trade-off between ATP and NADPH production for maintenance. This leads to a method for predicting cell maintenance costs on the basis of the measured flux ratio between the oxidative steps of the oxidative pentose phosphate pathway and glycolysis. We show that accounting for transport and maintenance costs substantially improves the accuracy of fluxes predicted from a flux balance model of heterotrophic Arabidopsis cells in culture, irrespective of the objective function used in the analysis. Moreover, when the new method was applied to cells under control, elevated temperature and hyper-osmotic conditions, only elevated temperature led to a substantial increase in cell maintenance costs. It is concluded that the hyper-osmotic conditions tested did not impose a metabolic stress, in as much as the metabolic network is not forced to devote more resources to cell maintenance.
通量平衡模型的新陈代谢通常利用生物量的合成作为细胞内通量的主要决定因素。然而，由于运输成本和细胞维持对能量预算的主要需求，仅靠生物量限制不足以预测植物细胞中心异养代谢的实际通量。通过将运输步骤纳入代谢模型，并实施一种使用帕累托最优分析来探索 ATP 和 NADPH 产生之间的权衡以维持的过程，可以解决这个主要限制。这导致了一种基于氧化戊糖磷酸途径和糖酵解的氧化步骤之间的测量通量比来预测细胞维持成本的方法。我们表明，考虑到运输和维持成本，从培养中的异养拟南芥细胞的通量平衡模型预测的通量的准确性大大提高，而不管分析中使用的目标函数如何。此外，当新方法应用于对照细胞、升高的温度和高渗条件下时，只有升高的温度导致细胞维持成本的大幅增加。结论是，测试的高渗条件没有施加代谢应激，因为代谢网络没有被迫将更多资源用于细胞维持。
