Bacterial adaptation through distributed sensing of metabolic fluxes.
Bacterial adaptation through distributed sensing of metabolic fluxes.
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DOI：
10.1038/msb.2010.10
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发表时间：
2010
影响因子：
9.9
通讯作者：
Heinemann, Matthias
中科院分区：
文献类型：
--
作者：
Kotte, Oliver;Zaugg, Judith B.;Heinemann, Matthias
碳源的识别和对已识别变化的调节对于细菌在波动环境中的存活具有特别重要的意义。尽管大肠杆菌的中央代谢及其调节的全面知识基础，所采用的传感和监管调整机制的基本方面仍然不清楚。本文利用微分方程模型，耦合酶和转录调控的E。大肠杆菌的中心代谢，我们表明已知相互作用的相互作用在分子水平上详细解释了糖酵解和糖异生碳源之间代谢操作的全系统调整。我们表明，这些适应是通过间接识别碳源通过一种机制，我们称之为分布式传感细胞内代谢通量。这种机制使用两个一般的基序来建立通量信号代谢物，其与转录因子的结合形成通量传感器。由于这些传感器嵌入在全局反馈回路架构中，因此闭环自我调节可以在代谢本身中出现，因此，代谢操作可以自主地（不需要上游传感和信号）适应波动的碳源。
The recognition of carbon sources and the regulatory adjustments to recognized changes are of particular importance for bacterial survival in fluctuating environments. Despite a thorough knowledge base of Escherichia coli's central metabolism and its regulation, fundamental aspects of the employed sensing and regulatory adjustment mechanisms remain unclear. In this paper, using a differential equation model that couples enzymatic and transcriptional regulation of E. coli's central metabolism, we show that the interplay of known interactions explains in molecular-level detail the system-wide adjustments of metabolic operation between glycolytic and gluconeogenic carbon sources. We show that these adaptations are enabled by an indirect recognition of carbon sources through a mechanism we termed distributed sensing of intracellular metabolic fluxes. This mechanism uses two general motifs to establish flux-signaling metabolites, whose bindings to transcription factors form flux sensors. As these sensors are embedded in global feedback loop architectures, closed-loop self-regulation can emerge within metabolism itself and therefore, metabolic operation may adapt itself autonomously (not requiring upstream sensing and signaling) to fluctuating carbon sources.
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