EAGER: Universal, programmable sensor-regulator elements for dynamic control and optimization of microbial biomanufacturing

微生物能产生许多有价值的产品。经济地生产这些产品的一个障碍是我们无法轻易地改变新陈代谢。这个项目将评估一类特定的蛋白质作为代谢开关。如果成功，这一策略将极大地扩展我们生物制造化学品的能力。该项目还将通过代表性不足的研究生和本科生的参与，培养多样化的生物技术劳动力。该项目将构建和表征新的温度和pH响应转录调控因子，这对更大的科学界具有广泛的兴趣。该项目还确立了这些系统作为代谢途径的可调、合成动态调节器的潜力。提出了一种模块化方法，其元素可以很容易地交换和调整，以实现对性能的完全控制。合成弹性蛋白样蛋白（ELPs）被应用于一个新的背景下，以识别细胞应激的一般指标。由于传感器的灵敏度是由ELP序列编程的，因此传感元件很容易适应许多过程。同样，转录因子控制元件可以与不同物种特异性的转录激活因子或抑制因子交换，以在不同的生产物种和控制模式中实现控制。该项目有望通过引入一种新的工具来优化新的生产途径，从而扩大可行产品的组合，从而帮助改变微生物化工厂的设计。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Microbes can produce many valuable products. One obstacle to making these products economically is our inability to easily redirect metabolism. This project will evaluate a specific class of proteins as a metabolic switch. If successful, the strategy could greatly expand our ability to manufacture chemicals biologically. This project will also develop a diverse biotechnology workforce through the involvement of underrepresented graduate and undergraduate students. The project will construct and characterize novel temperature and pH responsive transcriptional regulators that are of broad interest to the greater scientific community. The project also establishes the potential of these systems as tunable, synthetic dynamic regulators of metabolic pathways. A modular approach whose elements can be easily swapped and tuned for full control of performance is proposed. Synthetic elastin-like proteins (ELPs), are applied in a novel context to recognize generic indicators of cellular stress. As sensor sensitivity is programmed by ELP sequence, sensing elements are readily adapted to a number of processes. Similarly, the transcription factor controller element may be swapped with different species- specific transcriptional activators or repressors to effect control in diverse production species and control modes. This project is expected to help transform microbial chemical factory design by introducing a new tool for the optimization of novel production pathways, thus broadening the portfolio of feasible products.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.