代谢物必需性阐明了大肠埃希菌代谢的耐用性
Metabolite essentiality elucidates robustness of Escherichia coli metabolism
摘要：
复杂的生物系统在组织的各个层面上对遗传和环境的变化都非常强大。大肠杆菌代谢的许多生物学功能可以通过使用冗余或替代途径来抵抗单基因甚至多基因突变。因此，只有有限数量的基因被鉴定为对细胞是致命的。在这方面，以反应为中心的基因缺失研究在理解代谢稳健性方面具有局限性。在这里，我们报告使用通量总和，这是一个特定的代谢物周围的所有传入或传出通量在伪稳态条件下的总和，作为一个很好的保守属性，阐明这种鲁棒性的E。从代谢物的角度来看。的功能行为，以及对细胞生存至关重要的代谢产物的结构和进化特性，通过基于约束的通量分析扰动条件下进行了研究。必需代谢物能够保持稳定的通量总和，即使对严重的扰动，积极重新分配相关的通量。发现破坏通量和维持抑制细胞生长。这种分析代谢物必要性的方法提供了对细胞稳健性和伴随的脆弱性的深入了解，其可用于多种应用，包括用于治疗病原体的新药的开发。
英文摘要：
Complex biological systems are very robust to genetic and environmental changes at all levels of organization. Many biological functions of Escherichia coli metabolism can be sustained against single-gene or even multiple-gene mutations by using redundant or alternative pathways. Thus, only a limited number of genes have been identified to be lethal to the cell. In this regard, the reaction-centric gene deletion study has a limitation in understanding the metabolic robustness. Here, we report the use of flux-sum, which is the summation of all incoming or outgoing fluxes around a particular metabolite under pseudo-steady state conditions, as a good conserved property for elucidating such robustness of E. coli from the metabolite point of view. The functional behavior, as well as the structural and evolutionary properties of metabolites essential to the cell survival, was investigated by means of a constraints-based flux analysis under perturbed conditions. The essential metabolites are capable of maintaining a steady flux-sum even against severe perturbation by actively redistributing the relevant fluxes. Disrupting the flux-sum maintenance was found to suppress cell growth. This approach of analyzing metabolite essentiality provides insight into cellular robustness and concomitant fragility, which can be used for several applications, including the development of new drugs for treating pathogens.
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