Metabolism constitutes the basis of life, and the dynamics of metabolism dictate various cellular processes. However, exactly how metabolite dynamics are controlled remains poorly understood. By studying an engineered fatty acid-producing pathway as a model, we found that upon transcription activation a metabolic product from an unregulated pathway required seven cell cycles to reach to its steady state level, with the speed mostly limited by enzyme expression dynamics. To overcome this limit, we designed metabolic feedback circuits (MeFCs) with three different architectures, and experimentally measured and modeled their metabolite dynamics. Our engineered MeFCs could dramatically shorten the rise-time of metabolites, decreasing it by as much as 12-fold. The findings of this study provide a systematic understanding of metabolite dynamics in different architectures of MeFCs and have potentially immense applications in designing synthetic circuits to improve the productivities of engineered metabolic pathways.

中文翻译：

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代谢反馈电路可快速控制代谢动力学

代谢构成生命的基础，新陈代谢的动力学决定了各种细胞过程。但是，如何准确控制代谢物动力学仍然知之甚少。通过研究工程化的脂肪酸产生途径作为模型，我们发现转录激活后，来自不受调控途径的代谢产物需要七个细胞周期才能达到其稳态水平，其速度主要受酶表达动力学的限制。为了克服这个限制，我们设计了具有三种不同结构的代谢反馈电路（MeFC），并通过实验测量和建模了它们的代谢动力学。我们设计的MeFC可大大缩短代谢物的上升时间，最多可将其减少12倍。