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

EAGER：通用、可编程传感器调节器元件，用于微生物生物制造的动态控制和优化

• 批准号: 1836654
• 负责人: Kevin Solomon
• 金额: $ 9.92万
• 依托单位: Purdue University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-15 至 2019-10-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1836654&HistoricalAwards=false
• 关键词: EAGER; Universal; programmable; sensor; regulator

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.

微生物可以生产许多有价值的产品。在经济上制造这些产品的一个障碍是我们无法轻松地重定向代谢。该项目将评估特定类别的蛋白质作为代谢开关。如果成功，该策略可以大大扩展我们在生物学上生产化学物质的能力。该项目还将通过参与不足的毕业生和本科生的参与来发展多样的生物技术劳动力。该项目将构建和表征新的温度和pH响应式转录调节因子，这些调节剂对更大的科学界具有广泛的兴趣。该项目还确定了这些系统的潜力，作为代谢途径的可调，合成的动态调节剂。提出了一种模块化方法，其元素可以轻松地交换和调整以完全控制性能。合成弹性蛋白样蛋白（ELP）在新的环境中应用，以识别细胞应激的通用指标。由于传感器灵敏度通过ELP序列编程，因此感应元素很容易适应许多过程。同样，转录因子控制器元件可以用不同的物种特异性转录激活剂或阻遏物交换，以影响多种生产物种和控制模式的控制。预计该项目将通过引入一种新的工具来优化新型生产途径，从而扩大可行产品的投资组合，从而有助于改变微生物化学工厂的设计。该奖项反映了NSF的法定任务，并被认为是通过基金会的知识分子优点和更广泛影响的审查标准来通过评估来获得支持的。