The proteome is a terminal electron acceptor.
The proteome is a terminal electron acceptor.
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蛋白质组是末端电子受体。
DOI：
10.1101/2024.01.31.578293
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Phillips,Rob
中科院分区：
文献类型：
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作者：
Flamholz,AviI;Goyal,Akshit;Fischer,WoodwardW;Newman,DianneK;Phillips,Rob
微生物的新陈代谢非常灵活，即使可利用的营养物质与氧化还原态的生物量有很大差异，微生物也能生长。例如，大肠杆菌通过几种形式的发酵和呼吸，调整其生理机能，使其在还原和氧化的碳源上生长。为了了解这种代谢灵活性的限制和进化后果，我们开发了一个粗粒度的数学框架，将氧化还原化学与细胞资源分配的原则相结合。我们的模型继承了它们两个前身的关键品质：i）描述不同的代谢化学和ii）强制原子的同时平衡（例如，碳）、电子和能量（三磷酸腺苷）流动，如在氧化还原模型中，而iii）将生物质作为生长过程的产物和催化剂，如在资源分配模型中。组装呼吸，发酵和光合作用的综合模型澄清了关键的微生物学现象，包括证明自养生物比异养生物生长得更慢，因为细胞内还原碳的生产所施加的限制。我们的模型进一步预测，异养生长的改善相匹配的氧化还原状态的生物量的营养环境。通过对60,000个基因组和不同蛋白质组数据集的分析，我们发现了蛋白质确实积累了促进氧化还原匹配的氨基酸取代的证据。因此，我们提出了一种意想不到的基因组进化模式，其中由于对群体的氧化还原化学益处，仍然可以选择对蛋白质的个体生化或结构功能中性甚至有害的取代。
Microbial metabolism is impressively flexible, enabling growth even when available nutrients differ greatly from biomass in redox state.Escherichia coli, for example, rearranges its physiology to grow on reduced and oxidized carbon sources through several forms of fermentation and respiration. To understand the limits on and evolutionary consequences of this metabolic flexibility, we developed a coarse-grained mathematical framework coupling redox chemistry with principles of cellular resource allocation. Our models inherit key qualities from both of their antecedents: i) describing diverse metabolic chemistries and ii) enforcing the simultaneous balancing of atom (e.g., carbon), electron, and energy (adenosine triphosphate) flows, as in redox models, while iii) treating biomass as both the product and catalyst of the growth process, as in resource allocation models. Assembling integrated models of respiration, fermentation, and photosynthesis clarified key microbiological phenomena, including demonstrating that autotrophs grow more slowly than heterotrophs because of constraints imposed by the intracellular production of reduced carbon. Our model further predicted that heterotrophic growth is improved by matching the redox state of biomass to the nutrient environment. Through analysis of60,000 genomes and diverse proteomic datasets, we found evidence that proteins indeed accumulate amino acid substitutions promoting redox matching. We therefore propose an unexpected mode of genome evolution where substitutions neutral or even deleterious to the individual biochemical or structural functions of proteins can nonetheless be selected due to a redox-chemical benefit to the population.