Metabolic enzyme cost explains variable trade-offs between microbial growth rate and yield.
Metabolic enzyme cost explains variable trade-offs between microbial growth rate and yield.
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DOI：
10.1371/journal.pcbi.1006010
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发表时间：
2018-03
影响因子：
4.3
通讯作者：
Liebermeister W
中科院分区：
文献类型：
--
作者：
Wortel MT;Noor E;Ferris M;Bruggeman FJ;Liebermeister W
微生物可以使每次或每次消耗的营养物的子细胞数量最大化。这两种策略分别对应于酶高效或底物高效代谢途径的使用。在现实中，快速增长往往与浪费，产量效率低下的代谢，和一般的热力学平衡之间的增长速度和生物量产量已被提出来解释这一点。我们研究了增长率/产量权衡使用一种新的建模框架，酶通量成本最小化（EFCM），并假设的增长率直接取决于酶的投资，生物质生产率。在E.大肠杆菌，我们筛选了所有基本通量模式导致细胞合成，其特征在于它们的生长速率和产量，他们提供，并研究了所产生的速度/产量帕累托前沿的形状。通过改变模型参数，我们发现，速率/产量的权衡是不普遍的，但取决于代谢动力学和环境条件。一个突出的权衡出现在氧气有限的增长，其中产量效率低的途径支持2-3倍的增长率比产量效率高的途径。EFCM可广泛用于预测在不同营养水平、酶参数扰动和单个或多个基因敲除下的最佳代谢状态和生长速率。当细胞竞争营养时，那些生长得更快，每次产生更多后代的细胞受到自然选择的青睐。相比之下，当细胞需要在有限的营养供应下最大化细胞数量时，快速生长并不重要，有效利用营养（即高生物量产量）是必不可少的。这就提出了一个关于新陈代谢的基本问题：细胞能否同时实现高生长率和产量，或者这两个目标之间是否存在冲突？使用一种新的建模方法，称为酶通量成本最小化（EFCM），我们预测细胞生长速率，并发现生长速率/产量权衡和随后的偏好酶效率或底物效率的代谢途径是不普遍的，但取决于生长条件，如外部葡萄糖和氧气浓度。
Microbes may maximize the number of daughter cells per time or per amount of nutrients consumed. These two strategies correspond, respectively, to the use of enzyme-efficient or substrate-efficient metabolic pathways. In reality, fast growth is often associated with wasteful, yield-inefficient metabolism, and a general thermodynamic trade-off between growth rate and biomass yield has been proposed to explain this. We studied growth rate/yield trade-offs by using a novel modeling framework, Enzyme-Flux Cost Minimization (EFCM) and by assuming that the growth rate depends directly on the enzyme investment per rate of biomass production. In a comprehensive mathematical model of core metabolism in E. coli, we screened all elementary flux modes leading to cell synthesis, characterized them by the growth rates and yields they provide, and studied the shape of the resulting rate/yield Pareto front. By varying the model parameters, we found that the rate/yield trade-off is not universal, but depends on metabolic kinetics and environmental conditions. A prominent trade-off emerges under oxygen-limited growth, where yield-inefficient pathways support a 2-to-3 times higher growth rate than yield-efficient pathways. EFCM can be widely used to predict optimal metabolic states and growth rates under varying nutrient levels, perturbations of enzyme parameters, and single or multiple gene knockouts. When cells compete for nutrients, those that grow faster and produce more offspring per time are favored by natural selection. In contrast, when cells need to maximize the cell number at a limited nutrient supply, fast growth does not matter and an efficient use of nutrients (i.e. high biomass yield) is essential. This raises a basic question about metabolism: can cells achieve high growth rates and yields simultaneously, or is there a conflict between the two goals? Using a new modeling method called Enzymatic Flux Cost Minimization (EFCM), we predict cellular growth rates and find that growth rate/yield trade-offs and the ensuing preference for enzyme-efficient or substrate-efficient metabolic pathways are not universal, but depend on growth conditions such as external glucose and oxygen concentrations.
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影响因子：
16.6
作者：
通讯作者：
--
DOI：
10.1016/j.bbagen.2011.05.014
发表时间：
2011-10-01
影响因子：
3
作者：
Goelzer, A.;Fromion, V.
通讯作者：
Fromion, V.
影响因子：
5.8
作者：
Liebermeister, Wolfram;Uhlendorf, Jannis;Klipp, Edda
通讯作者：
Klipp, Edda
影响因子：
2.8
作者：
Bekker, M.;Kramer, G.;de Mattos, M. J. Teixeira
通讯作者：
de Mattos, M. J. Teixeira
DOI：
10.1073/pnas.1308523110
发表时间：
2013-08-27
影响因子：
11.1
作者：
Bachmann, Herwig;Fischlechner, Martin;Teusink, Bas
通讯作者：
Teusink, Bas