Large-scale in vivo flux analysis shows rigidity and suboptimal performance of Bacillus subtilis metabolism
Large-scale in vivo flux analysis shows rigidity and suboptimal performance of Bacillus subtilis metabolism
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DOI：
10.1038/ng1555
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发表时间：
2005-06-01
期刊：
影响因子：
30.8
通讯作者：
Sauer, U
中科院分区：
文献类型：
--
作者：
Fischer, E;Sauer, U
定性的理论方法，如图论（1，2）和化学计量分析（3-6）开始揭示复杂的代谢反应网络的结构和系统功能。然而，目前，只有少数几个，很大程度上未经证实的定量概念提出了功能设计原则的全球通量分布（7，8）。作为功能的操作单位，分子通量通过将基因、蛋白质和代谢物与更高水平的生物功能联系起来来决定系统性细胞表型（9）。与其他“组学”分析形成鲜明对比，“通量组”分析仍然繁琐（10）。通过大规模的体内通量响应的定量，我们确定了一个强大的通量分布在137无效突变体的枯草芽孢杆菌。在其优选的基底上，B。枯草芽孢杆菌具有次优代谢，因为发育程序的调节器保持“待机”模式，该模式以最优生长为代价投资大量资源以预期变化的环境条件。网络刚性和鲁棒性可能是通用的功能设计原则，而待机模式可能更具体。
Qualitative theoretical approaches such as graph theory(1,2) and stoichiometric analyses(3-6) are beginning to uncover the architecture and systemic functions of complex metabolic reaction networks. At present, however, only a few, largely unproven quantitative concepts propose functional design principles of the global flux distribution(7,8). As operational units of function, molecular fluxes determine the systemic cell phenotype by linking genes, proteins and metabolites to higher-level biological functions(9). In sharp contrast to other 'omics' analyses, 'fluxome' analysis remained tedious(10). By large-scale quantification of in vivo flux responses, we identified a robust flux distribution in 137 null mutants of Bacillus subtilis. On its preferred substrate, B. subtilis has suboptimal metabolism because regulators of developmental programs maintain a 'standby' mode that invests substantial resources in anticipation of changing environmental conditions at the expense of optimal growth. Network rigidity and robustness are probably universal functional design principles, whereas the standby mode may be more specific.