Model-based Engineering of Metabolism in Microbial Cells and Communities

微生物细胞和群落代谢的基于模型的工程

• 批准号: RGPIN-2016-06215
• 负责人: Mahadevan, Radhakrishnan
• 金额: $ 2.4万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=616166
• 关键词: Model; based; Engineering; Metabolism; Microbial

Metabolism is the source of energy required for powering cellular processes in all living things. Understanding metabolism in an integrated way allows the opportunity to harness the power of natural metabolic networks for several applications including the manufacture of renewable fuels and non-natural chemicals, clean-up of contaminated groundwater, and potentially for maintaining a healthy gut microbiome through nutritional and probiotic interventions. However, there are several challenges in engineering metabolism for these practical applications. A key limitation is the ability to quantitatively describe the dynamics of metabolic transience within the cells and the metabolic interactions with other species in microbial communities. Further, novel tools to manipulate metabolism in a dynamic manner will enable the precise engineering of metabolism. Hence, the objectives of the proposal are the development of modeling and optimization frameworks for large-scale metabolic networks in cells and communities along with experimental tools for the dynamic control of metabolic pathways. The ultimate objective is the application of these tools for the development of commercializable bioprocess for the manufacture of non-natural chemicals and model-based design for personalized nutrition and medicine.

新陈代谢是所有生物细胞过程所需能量的来源。以一种综合的方式理解代谢，可以让我们有机会利用自然代谢网络的力量进行多种应用，包括制造可再生燃料和非天然化学品，清理受污染的地下水，以及通过营养和益生菌干预维持健康的肠道微生物群。然而，在这些实际应用中，工程代谢存在一些挑战。一个关键的限制是能够定量描述细胞内代谢瞬态的动力学以及微生物群落中与其他物种的代谢相互作用。此外，以动态方式操纵代谢的新工具将使代谢的精确工程成为可能。因此，该提案的目标是开发细胞和群落中大规模代谢网络的建模和优化框架，以及代谢途径动态控制的实验工具。最终目标是将这些工具用于开发可商业化的生物工艺，用于制造非天然化学品和个性化营养和药物的基于模型的设计。