期刊
ACS SYNTHETIC BIOLOGY
卷 6, 期 10, 页码 1851-1859出版社
AMER CHEMICAL SOC
DOI: 10.1021/acssynbio.7b00172
关键词
metabolite biosensor; dynamic pathway regulation; metabolic engineering; transcriptional regulator; pathway optimization; model-based design
资金
- Human Frontier Science Program [RGY0076-2015]
- US National Science Foundation [MCB1453147]
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.
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