Fundamental Design Principles for Transcription-Factor-Based Metabolite Biosensors
Fundamental Design Principles for Transcription-Factor-Based Metabolite Biosensors
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DOI：
10.1021/acssynbio.7b00172
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发表时间：
2017-10-01
影响因子：
4.7
通讯作者：
Oyarzun, Diego A.
中科院分区：
文献类型：
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作者：
Mannan, Ahmad A.;Liu, Di;Oyarzun, Diego A.
代谢物生物传感器是当前代谢精确工程的核心，尽管大多数研究都集中在构建新的生物传感器上，但其可调性仍然知之甚少，并且是其广泛应用的基础。在这里，我们询问遗传修饰如何塑造基于代谢物反应转录因子的生物传感器的剂量反应曲线。以EscWrichia colt中的lac系统为模型系统，我们构建了具有可变操作点的启动子文库，揭示了生物传感器动态范围和响应阈值之间的相互依赖关系。我们开发了一种现象学理论来量化具有不同结构和可调参数的生物传感器中的此类设计约束。我们的理论揭示了最大可实现的动态范围，并为动态范围和响应阈值的正交控制提供了可调的参数。我们的工作揭示了合成生物学设计的基本极限，并为生物传感器设计在动态路径控制、菌株优化和代谢实时监测等应用中提供了定量指导。
Metabolite biosensors are central to current efforts toward precision engineering of metabolism Although most research has focused on building new biosensors, their tunability remains poorly understood and is fundamental for their broad applicability. Here we asked how genetic modifications shape the dose response curve of biosensors based on metabolite-responsive transcription factors. Using the lac system in EscWrichia colt as a model system, we built promoter libraries with variable operator sites that reveal interdependencies between biosensor dynamic range and response threshold. We developed a phepomenological theory to quantify such design constraints in biosensors with various architectures and tunable parameters. Our theory reveals a maximal achievable dynamic range and exposes tunable Parameters for orthogonal control of dynamic range and response threshold. Our work sheds light on fundamental limits of synthetic biology designs and provides quantitative guidelines for biosensor design in applications such as dynamic pathway control, strain optimization, and real-time monitoring of metabolism.