Center for Quantitative Biology, School of Physics and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, 100871, China.
Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
Nat Commun. 2019 Mar 20;10(1):1279. doi: 10.1038/s41467-019-09261-3.
A classic problem in microbiology is that bacteria display two types of growth behavior when cultured on a mixture of two carbon sources: the two sources are sequentially consumed one after another (diauxie) or they are simultaneously consumed (co-utilization). The search for the molecular mechanism of diauxie led to the discovery of the lac operon. However, questions remain as why microbes would bother to have different strategies of taking up nutrients. Here we show that diauxie versus co-utilization can be understood from the topological features of the metabolic network. A model of optimal allocation of protein resources quantitatively explains why and how the cell makes the choice. In case of co-utilization, the model predicts the percentage of each carbon source in supplying the amino acid pools, which is quantitatively verified by experiments. Our work solves a long-standing puzzle and provides a quantitative framework for the carbon source utilization of microbes.
微生物学中的一个经典问题是，当细菌在两种碳源的混合物中培养时，会表现出两种生长行为：两种来源依次被消耗（双相生长）或同时被消耗（共利用）。对双相生长分子机制的研究导致了 lac 操纵子的发现。然而，人们仍然不清楚微生物为什么会有不同的吸收营养物质的策略。在这里，我们展示了从代谢网络的拓扑特征可以理解双相生长与共利用之间的差异。一个蛋白质资源最优分配的模型定量解释了细胞为什么以及如何做出选择。在共利用的情况下，该模型预测了每种碳源在供应氨基酸池中的比例，实验结果定量验证了这一预测。我们的工作解决了一个长期存在的难题，并为微生物利用碳源提供了一个定量框架。
