基于溢流代谢调控的富马酸合成路径改造研究

微生物细胞工厂能够将可再生生物质资源大规模转化为人类所需的能源、化工、医药、食品及农业原材料。然而，由于大部分微生物细胞工厂的构建，需要引入部分或完整异源代谢途径，因此，容易引起溢流代谢。本项目通过设计富马酸合成途径、构建富马酸合成前体库、优化富马酸还原路径底物传输效率、阻断富马酸的分解代谢路径，逐步降低富马酸合成过程中的溢流代谢，提高富马酸的合成效率。所采用的研究思路和设计方法对其他化学品高效合成路径的构建与解析具有一定的参考价值，同时对代谢工程中未知限速途径酶的调控研究也具有一定的借鉴意义。

Microbial cell factories (MCF) are capable of transforming renewable biomass resources into raw materials for energy, chemical, pharmacy, food and agriculture. However, when MCF are constructed, the multi-gene pathways are introduced. This process usually gives rise to metabolic imbalance and intermediate metabolite accumulation, thus rsulting in serious overflow metabolism and low substrate transmission efficiency. In this project, these bottlenecks for fumarate production are progressively solved to enhance the efficiency of producing fumarate by designing the optimal fumarate biosynthetic pathway, constructing the precursor pool for fumarate production, optimizing intermediate metabolites transmission efficiency in the reductive pathway, blocking branch pathways for fumarate metabolism. The research strategies and idea used in this project are not only useful for the construction of the metabolic pathway for the other chemicals, but also are academic value for the studies of the unknown pathway enzymes in metabolic engineering.