Enhanced Production of Advanced Biofuels through Model Guided Synthetic Biology

通过模型引导合成生物学提高先进生物燃料的生产

• 批准号: 1437836
• 负责人: Mark Blenner
• 金额: $ 31.39万
• 依托单位: Clemson University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1437836&HistoricalAwards=false
• 关键词: Enhanced; Production; Advanced; Biofuels; through

Principal Investigator: Mark BlennerNumber: 1437836This project seeks to improve the production of biodiesel in a genetically engineered strain of bacteria by understanding how sugars are converted into biodiesel. This will be accomplished through cell-based monitoring of the microorganism?s metabolism control processes through the principles of synthetic biology, which look holistically at how all metabolic processes within a cell interact with one another. A second aim of this project is control these metabolic processes to maintain high biodiesel production rates under changing environmental or process conditions. The results of this project may also apply to other metabolic pathways that produce sustainable fuels and chemicals, allowing transfer of these techniques from the laboratory to industry with more certainty and fewer complications. The project activities will also include efforts to engage women potentially interested in science, technology, engineering, and mathematics (STEM) careers in the state of South Carolina. Education and research will be integrated by providing training opportunities for students already in STEM, and local outreach to young women who might become more interested in STEM. Finally, this research will be integrated into a new elective course on protein and metabolic engineering offered at Clemson University. Technical DescriptionThis project will use simple unsteady-state kinetic models to rationalize protein engineering and synthetic biology based improvements to E. coli biodiesel production. Preliminary modeling studies identify inefficiencies due to pathway imbalance, and suggest that better flux distributions can be achieved through genetic and protein engineering efforts. Enzymes with catalytic efficiencies predicted to improve biodiesel production will be used. Critical enzymes will be engineered using directed evolution to relieve pathway bottlenecks. Protein-level feedback control will be engineered and combined with genetic level feedback control to allow pathway fluxes to remain high in spite of short and long time-scale metabolic perturbations. The combination of genetic and protein-level dynamic control will allow biofuel and other chemical producing systems to withstand perturbations from environmental variation and scale-up conditions without suffering large losses in yield and efficiency. The results of this project may lead to more general methods for balancing pathways that does not rely on explicit kinetic or flux data. The project activities will also include efforts to engage women potentially interested in science, technology, engineering, and mathematics (STEM) careers in the state of South Carolina. Education and research will be integrated by providing training opportunities for students already in STEM, and local outreach to young women who might become more interested in STEM. Finally, this research will be integrated into a new elective course on protein and metabolic engineering offered at Clemson University.

首席研究员：Mark Blenner 编号：1437836 该项目旨在通过了解糖如何转化为生物柴油来提高基因工程细菌菌株的生物柴油产量。 这将通过合成生物学原理对微生物代谢控制过程进行细胞监测来实现，合成生物学原理全面观察细胞内所有代谢过程如何相互作用。 该项目的第二个目标是控制这些代谢过程，以在不断变化的环境或过程条件下保持高生物柴油生产率。该项目的结果也可能适用于生产可持续燃料和化学品的其他代谢途径，从而使这些技术能够以更高的确定性和更少的复杂性从实验室转移到工业界。该项目活动还将包括努力吸引南卡罗来纳州对科学、技术、工程和数学 (STEM) 职业感兴趣的女性。 教育和研究将结合起来，为已经学习 STEM 的学生提供培训机会，并在当地向可能对 STEM 更感兴趣的年轻女性进行宣传。最后，这项研究将被纳入克莱姆森大学提供的蛋白质和代谢工程新选修课程中。 技术描述该项目将使用简单的非稳态动力学模型来合理化基于蛋白质工程和合成生物学的大肠杆菌生物柴油生产改进。初步建模研究发现了由于途径不平衡导致的效率低下，并表明可以通过基因和蛋白质工程努力实现更好的通量分布。将使用预计可提高生物柴油产量的催化效率酶。 将使用定向进化来设计关键酶，以缓解途径瓶颈。蛋白质水平反馈控制将被设计并与基因水平反馈控制相结合，以允许通路通量在短期和长期代谢扰动的情况下保持较高水平。遗传和蛋白质水平动态控制的结合将使生物燃料和其他化学品生产系统能够承受环境变化和规模化条件的干扰，而不会遭受产量和效率的巨大损失。该项目的结果可能会产生更通用的方法来平衡不依赖于显式动力学或通量数据的路径。该项目活动还将包括努力吸引南卡罗来纳州对科学、技术、工程和数学 (STEM) 职业感兴趣的女性。 教育和研究将结合起来，为已经学习 STEM 的学生提供培训机会，并在当地向可能对 STEM 更感兴趣的年轻女性进行宣传。最后，这项研究将被纳入克莱姆森大学提供的蛋白质和代谢工程新选修课程中。