EAGER: Dynamic Flux Control Enabled by Synthetic Metabolic Valves

EAGER项目由MCB的系统和合成生物学计划以及可持续发展能源计划资助，将导致新工具的开发，使研究人员能够在化学品的生物制造过程中以精确的方式控制碳，能量和其他资源在细胞中的分配。 这将允许碳和能量从细胞生长转移到产物形成，这将增加产物产量。 此外，这些工具可以从生物制造中使用的细菌转移到其他生物体，并用于解决有关这些系统中代谢控制和调节的基本问题。 研究员将在跨学科环境中培训研究生和本科生，并指导参加国际遗传工程机器（iGEM）竞赛的本科生，这是一项国际竞赛，通过要求年轻人设计和构建微生物的新功能来吸引科学和工程领域的年轻人。该项目旨在开发代谢途径中的灵活（可控）阀门，使碳通量通过途径被随意重新定向。这将使微生物代谢的动态优化，将代谢通量从与生长相关的途径转移到与产物形成相关的途径。研究人员将使用CRISPRi基因沉默技术结合受控的酶降解来实现所需的碳通量。然后，研究人员将通过详细的代谢通量测量来测试这些策略的有效性。 这些工具不仅可以改善当前的代谢工程和合成生物学实践，从而影响可再生化学品的生物制造，而且如果可以转移到其他宿主，该技术可以用于解决有关代谢和代谢途径调节的重要问题。

This EAGER project, funded by the Systems and Synthetic Biology program in MCB and the Energy for Sustainability program, will lead to the development of new tools that will enable investigators to control the allocation of carbon, energy, and other resources in cells in a precise way during the biomanufacture of chemicals. This will allow carbon and energy to be diverted from cell growth to product formation, which should increase product yield. In addition, the tools could be transferred from bacteria used in biomanufacturing to other organisms, and used to address fundamental questions about control and regulation of metabolism in these systems. The investigator will train graduate and undergraduate students in an interdisciplinary environment and mentor undergraduates who participate in the International Genetically Engineering Machine (iGEM) competition, an international competition that engages young people in science and engineering by asking them to design and build new function into microorganisms.Technical Description: This project aims to develop flexible (controllable) valves in metabolic pathways that will allow carbon flux through pathways to be redirected at will. This would enable the dynamic optimization of microbial metabolism, shifting metabolic flux from pathways associated with growth to those associated with product formation. Researchers will use CRISPRi gene silencing technologies coupled with controlled enzyme degradation to achieve the desired carbon flux. The researchers will then test the effectiveness of these strategies thru detailed metabolic flux measurements. The tools could not only improve current metabolic engineering and synthetic biology practices, and thus impact biomanufacturing of renewable chemicals, but if transferable to other hosts, the technology could be used to address important questions about regulation of metabolism and metabolic pathways.