On the optimality of the enzyme-substrate relationship in bacteria.

On the optimality of the enzyme-substrate relationship in bacteria.
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关于细菌中酶 - 基底关系的最佳性。

DOI:
10.1371/journal.pbio.3001416
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发表时间:
2021-10
期刊:
影响因子:
9.8
通讯作者:
Lercher MJ
Lercher MJ
中科院分区:
生物学1区
文献类型:
--
作者:
Dourado H;Mori M;Hwa T;Lercher MJ

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最近已经取得了很大的进展,了解蛋白质组分配对细菌生长的影响,少得多的是已知的酶和它们的底物,共同决定代谢通量的丰度之间的关系。在这里,我们报告了大肠杆菌中的酶和它们的底物的浓度之间的相关性。我们认为这种关系是最佳资源分配的结果,受到生物质密度的总体约束:对于由有效不可逆反应组成的细胞反应网络,当分配给每个基质的干质量等于不饱和有机物的干质量时,基于这种最优性原理的计算成功地预测了所观察到的酶和代谢物丰度之间的定量关系,仅通过分子量和酶-底物解离常数(Km)参数化。相应的组织原理为细胞投资于不同类型的分子提供了基本原理,这可能有助于设计更有效的合成细胞系统。本研究表明,在E.在大肠杆菌中,每种代谢物的细胞质量大约等于等待消耗它的游离酶的组合质量;这种简单的关系源于细胞干质量的最佳利用,并定量地描述了可用的实验数据。
Much recent progress has been made to understand the impact of proteome allocation on bacterial growth; much less is known about the relationship between the abundances of the enzymes and their substrates, which jointly determine metabolic fluxes. Here, we report a correlation between the concentrations of enzymes and their substrates in Escherichia coli. We suggest this relationship to be a consequence of optimal resource allocation, subject to an overall constraint on the biomass density: For a cellular reaction network composed of effectively irreversible reactions, maximal reaction flux is achieved when the dry mass allocated to each substrate is equal to the dry mass of the unsaturated (or “free”) enzymes waiting to consume it. Calculations based on this optimality principle successfully predict the quantitative relationship between the observed enzyme and metabolite abundances, parameterized only by molecular masses and enzyme–substrate dissociation constants (Km). The corresponding organizing principle provides a fundamental rationale for cellular investment into different types of molecules, which may aid in the design of more efficient synthetic cellular systems. This study shows that in E. coli, the cellular mass of each metabolite approximately equals the combined mass of the free enzymes waiting to consume it; this simple relationship arises from the optimal utilization of cellular dry mass, and quantitatively describes available experimental data.
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