Dept. Molecular and Statistical Physics, SISSA - International School for Advanced Studies, Trieste, Italy.
ICTP- International Centre of Theoretical Physics, Trieste, Italy.
Sci Rep. 2016 Jun 10;6:27660. doi: 10.1038/srep27660.
A way to decipher the complexity of the cellular metabolism is to study the effect of different external perturbations. Through an analysis over a sufficiently large set of gene knockouts and growing conditions, one aims to find a unifying principle that governs the metabolic regulation. For instance, it is known that the cessation of the microorganism proliferation after a gene deletion is only transient. However, we do not know the guiding principle that determines the partial or complete recovery of the growth rate, the corresponding redistribution of the metabolic fluxes and the possible different phenotypes. In spite of this large variety in the observed metabolic adjustments, we show that responses of E. coli to several different perturbations can always be derived from a sequence of greedy and myopic resilencings. This simple mechanism provides a detailed explanation for the experimental dynamics both at cellular (proliferation rate) and molecular level ((13)C-determined fluxes), also in case of appearance of multiple phenotypes. As additional support, we identified an example of a simple network motif that is capable of implementing this myopic greediness in the regulation of the metabolism.
一种破译细胞代谢复杂性的方法是研究不同外部干扰的影响。通过对大量基因敲除和生长条件的分析，旨在找到一种统御代谢调控的普遍原理。例如，已知微生物在基因缺失后停止增殖只是暂时的。然而，我们并不知道决定生长速率的部分或完全恢复、相应的代谢通量再分配以及可能的不同表型的指导原则。尽管观察到的代谢调整存在很大的多样性，但我们表明，大肠杆菌对几种不同干扰的反应总是可以从一系列贪婪和短视的弹性中推导出来。这种简单的机制为细胞水平（增殖率）和分子水平（（13）C 确定的通量）的实验动态提供了详细的解释，即使出现多种表型也是如此。作为额外的支持，我们确定了一个简单的网络基元的例子，该基元能够在代谢调控中实现这种短视的贪婪。
