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Conservation of high-flux backbone in alternate optimal and near-optimal flux distributions of metabolic networks

机译:高通量骨架在代谢网络的交替最佳和接近最佳通量分布中的守恒

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摘要

Constraint-based flux balance analysis (FBA) has proven successful in predicting the flux distribution of metabolic networks in diverse environmental conditions. FBA finds one of the alternate optimal solutions that maximizes the biomass production rate. Almaas et al. have shown that the flux distribution follows a power law, and it is possible to associate with most metabolites two reactions which maximally produce and consume a given metabolite, respectively. This observation led to the concept of high-flux backbone (HFB) in metabolic networks. In previous work, the HFB has been computed using a particular optima obtained using FBA. In this paper, we investigate the conservation of HFB of a particular solution for a given medium across different alternate optima and near-optima in metabolic networks of E. coli and S. cerevisiae. Using flux variability analysis (FVA), we propose a method to determine reactions that are guaranteed to be in HFB regardless of alternate solutions. We find that the HFB of a particular optima is largely conserved across alternate optima in E. coli, while it is only moderately conserved in S. cerevisiae. However, the HFB of a particular near-optima shows a large variation across alternate near-optima in both organisms. We show that the conserved set of reactions in HFB across alternate near-optima has a large overlap with essential reactions and reactions which are both uniquely consuming (UC) and uniquely producing (UP). Our findings suggest that the structure of the metabolic network admits a high degree of redundancy and plasticity in near-optimal flow patterns enhancing system robustness for a given environmental condition.
机译:基于约束的通量平衡分析(FBA)已被证明可以成功预测各种环境条件下代谢网络的通量分布。亚马逊物流找到了可最大化生物质生产率的替代性最佳解决方案之一。 Almaas等。已经表明通量分布遵循幂定律,并且可以与大多数代谢物相关联的两个反应分别最大地产生和消耗给定的代谢物。这一发现导致了代谢网络中高通量骨架(HFB)的概念。在以前的工作中,已使用通过FBA获得的特定最佳值来计算HFB。在本文中,我们研究了特定溶液的HFB在大肠杆菌和酿酒酵母的代谢网络中,在不同的最佳和接近最佳条件下,对于给定培养基的保存情况。使用通量变异性分析(FVA),我们提出了一种确定反应的方法,该反应可确保在HFB中,无论替代解决方案如何。我们发现,特定最佳蛋白的HFB在大肠杆菌中的其他最佳蛋白之间在很大程度上是保守的,而在酿酒酵母中则只是中等程度的保守。但是,在两种生物中,特定接近最佳状态的HFB在不同的接近最佳状态之间显示出很大的差异。我们显示,在HFB中,交替交替的接近最优的守恒反应集与基本反应和既是唯一消耗(UC)又是唯一产生(UP)的反应有很大的重叠。我们的发现表明,在给定的环境条件下,代谢网络的结构在接近最佳的流动模式中具有高度的冗余性和可塑性,从而增强了系统的鲁棒性。

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