代谢优化中的自发反应沉默
Spontaneous Reaction Silencing in Metabolic Optimization
摘要：
单细胞生物体的代谢反应通常被观察到在某些情况下变得异常或甚至不能进行活性。然而，与这种行为相关的机制以及条件和表型的范围仍然知之甚少。在这里，我们预测计算和分析，任何生物体进化到最大限度地提高生长速度，ATP生产，或任何其他线性函数的代谢通量往往显着减少活跃的代谢反应的数量相比，典型的非最佳状态。减少的数量在所研究的微生物物种中似乎是恒定的，并且仅略大于生物体生长所需的最小数量。我们发现，这种大规模的自发反应沉默是由大部分代谢反应的不可逆性引发的，并通过网络传播作为一个级联的不活动。我们的研究结果有助于解释现有的细胞内通量测量和潜在途径的使用实验数据，为微生物进化，鲁棒性和执行特定生化任务的多功能性提供新的线索。特别是，最佳反应活性的鉴定为最近提出的用于代谢功能的合成恢复的有趣的基于敲除的方法提供了严格的基础。
英文摘要：
Metabolic reactions of single-cell organisms are routinely observed to become dispensable or even incapable of carrying activity under certain circumstances. Yet, the mechanisms as well as the range of conditions and phenotypes associated with this behavior remain very poorly understood. Here we predict computationally and analytically that any organism evolving to maximize growth rate, ATP production, or any other linear function of metabolic fluxes tends to significantly reduce the number of active metabolic reactions compared to typical non-optimal states. The reduced number appears to be constant across the microbial species studied and just slightly larger than the minimum number required for the organism to grow at all. We show that this massive spontaneous reaction silencing is triggered by the irreversibility of a large fraction of the metabolic reactions and propagates through the network as a cascade of inactivity. Our results help explain existing experimental data on intracellular flux measurements and the usage of latent pathways, shedding new light on microbial evolution, robustness, and versatility for the execution of specific biochemical tasks. In particular, the identification of optimal reaction activity provides rigorous ground for an intriguing knockout-based method recently proposed for the synthetic recovery of metabolic function.
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