An analytical theory of balanced cellular growth
An analytical theory of balanced cellular growth
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DOI：
10.1038/s41467-020-14751-w
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发表时间：
2020-03-06
影响因子：
16.6
通讯作者：
Lercher, Martin J.
中科院分区：
文献类型：
--
作者：
Dourado, Hugo;Lercher, Martin J.
微生物的生物适合性在很大程度上取决于它们复制其生物量组成的速度。在考虑质量守恒、反应动力学和单位体积干质量限制的同时，最大化这种平衡增长率的数学模型不可避免地是非线性的。在这里，我们为这些模型开发了一个通用理论，称为生长平衡分析(GBA)，它提供了蛋白质浓度、通量和生长速度的显式表达式。这些变量是细胞成分浓度的函数，为此，我们计算与代谢控制系数相关的边际适应成本和收益。在最大增长率下，所有集中度的净效益是相等的。GBA仅基于物理化学约束，揭示了细胞资源分配和生长的基本量化原理；它准确地预测了大肠杆菌和酵母中的生长速度和核糖体浓度之间的关系，以及大肠杆菌中的生长速度和干质量密度之间的关系。
The biological fitness of microbes is largely determined by the rate with which they replicate their biomass composition. Mathematical models that maximize this balanced growth rate while accounting for mass conservation, reaction kinetics, and limits on dry mass per volume are inevitably non-linear. Here, we develop a general theory for such models, termed Growth Balance Analysis (GBA), which provides explicit expressions for protein concentrations, fluxes, and growth rates. These variables are functions of the concentrations of cellular components, for which we calculate marginal fitness costs and benefits that are related to metabolic control coefficients. At maximal growth rate, the net benefits of all concentrations are equal. Based solely on physicochemical constraints, GBA unveils fundamental quantitative principles of cellular resource allocation and growth; it accurately predicts the relationship between growth rates and ribosome concentrations in E. coli and yeast and between growth rate and dry mass density in E. coli.