GOALI: Advanced biomanufacturing with inducible feedback promoters

目标：具有诱导反馈启动子的先进生物制造

• 批准号: 1803747
• 负责人: Julius Lucks
• 金额: $ 50万
• 依托单位: Northwestern 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: 2018-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1803747&HistoricalAwards=false
• 关键词: GOALI; Advanced; biomanufacturing; inducible; feedback

Producing chemicals using microbes and biomass is an alternative to processes that use petroleum as a raw material. Performing this at a commercial scale is difficult. This project will develop a new tool to improve microbial chemical production. The tool will use the microbe's ability to sense its environment to improve performance. The microbes will produce a variety of industrial chemicals. Outreach to the community will take many forms. One involves hands-on demonstrations in a local high school and elementary school serving underrepresented populations. The broader public will be engaged through booths at Chicago-area Maker Faires. These activities are designed to stimulate interest in biology as a tool to solve societal challenges. They should also expand the pool of students pursuing STEM careers and entering the biomanufacturing workforce.IFPs (inducible feedback promoters) represent a new regulatory concept for metabolic pathway control and optimization. They combine naturally occurring stress responsive feedback with purely inducible timing control. Inducibility allows titration and timing of pathway expression to be rapidly explored. Stress responsive feedback allows autonomous expression optimization. The central objective is to develop and validate IFPs in the context of two industrially important metabolic pathways: terpenoid oxygenation and n-butanol production. This objective will be pursued through aims that validate the approach of IFP regulation in each pathway. We will create a community resource of unique IFPs applicable to diverse metabolic pathways. IFPs that are directly relevant for industrial bioprocess application will be fine-tuned using autonomous timing control through quorum-sensing and biosensors. These efforts will be done in collaboration with industry partners who will provide critical perspective to allow development of IFPs that provide the greatest possible value to industry.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.

使用微生物和生物质生产化学品是使用石油作为原材料的工艺的替代方案。以商业规模执行此操作很困难。该项目将开发一种新工具来提高微生物化学品的生产。该工具将利用微生物感知其环境的能力来提高性能。这些微生物将产生多种工业化学品。与社区的接触将采取多种形式。其中一项涉及在当地一所高中和小学为弱势群体提供实践示范。更广泛的公众将通过芝加哥地区创客博览会的展位参与其中。这些活动旨在激发人们对生物学作为解决社会挑战的工具的兴趣。他们还应该扩大追求 STEM 职业并进入生物制造劳动力的学生群体。IFP（诱导反馈促进剂）代表了代谢途径控制和优化的新监管概念。它们将自然发生的压力响应反馈与纯粹诱导的时间控制结合起来。诱导性允许快速探索途径表达的滴定和时间。压力响应反馈允许自主表达优化。中心目标是在两个工业上重要的代谢途径（萜类氧化和正丁醇生产）的背景下开发和验证 IFP。这一目标将通过在每个途径中验证 IFP 监管方法的目标来实现。我们将创建适用于多种代谢途径的独特 IFP 社区资源。与工业生物过程应用直接相关的 IFP 将通过群体感应和生物传感器使用自主定时控制进行微调。这些努力将与行业合作伙伴合作完成，他们将提供批判性视角，以允许开发为行业提供最大可能价值的 IFP。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力优势和能力进行评估，被认为值得支持。更广泛的影响审查标准。

项目成果

Dynamic Control of Gene Expression with Riboregulated Switchable Feedback Promoters

用核糖调节的可切换反馈启动子动态控制基因表达

• DOI: 10.1021/acssynbio.1c00015
• 发表时间: 2021-04
• 期刊: ACS Synthetic Biology
• 影响因子: 4.7
• 作者: Glasscock, Cameron J.;Biggs, Bradley W.;Lazar, John T.;Arnold, Jack H.;Burdette, Lisa A.;Valdes, Aliki;Kang, Min;Tullman;Tyo, Keith E.;Lucks, Julius B.
• 通讯作者: Lucks, Julius B.