Model-based Engineering of Metabolism in Microbial Cells and Communities

新陈代谢是为所有生物的细胞过程提供动力所需的能量来源。以综合的方式了解新陈代谢，使我们有机会利用自然新陈代谢网络的力量，用于多种应用，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，并有可能通过营养和益生菌干预来维持健康的肠道微生物群。然而，对于这些实际应用，在工程新陈代谢方面存在一些挑战。一个关键的限制是定量描述细胞内代谢瞬变的动态以及与微生物群落中其他物种的代谢相互作用的能力。此外，以动态方式操纵新陈代谢的新工具将使新陈代谢的精确工程成为可能。因此，该提案的目标是为细胞和社区中的大规模代谢网络开发建模和优化框架，以及用于动态控制代谢途径的实验工具。最终目标是将这些工具应用于开发可商业化的生物工艺，用于非天然化学品的生产和个性化营养和药物的基于模型的设计。

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.