苹果酸合成路径的碳流封存调控及其机制解析

微生物细胞工厂合成化学品过程中，目标产品的得率受到合成路径碳流封存效率的制约。然而，如何进行目标产品合成路径的碳流封存调控及其作用机制尚不清晰。本项目以E. coli中苹果酸合成路径为研究模型，借助计算生物学、合成生物学、代谢工程和组学分析等研究手段，通过构建与优化CO2羧化固定型苹果酸合成路径、设计与重构人造CO2固定途径、失活与进化TCA循环CO2释放步骤等策略调控碳流封存效率，并结合生理参数和组学数据，阐明苹果酸合成路径的碳流封存调控作用机制。本项目进一步增强了对碳流封存调控机制的理解，同时也为其它化学品高产菌株选育和生产路线优化提供了理论基础，因此具有重要的理论和实践意义。

During the process of chemicals synthesis with microbial cell factories, the yield of target products is restricted by carbon sequestration efficiency of its biosynthetic pathway. However, how to regulate carbon sequestration and its mechanism of the biosynthetic pathway for target products is still unclear. In this project, with the biosynthetic pathway of malate in E. coli as a as research model, carbon sequestration efficiency was first regulated by engineering the CO2-carboxylating pathway for malate biosynthesis, creating the artificial pathway for CO2 fixation, and evolving the functional inactivation pathway for CO2 release. Then, the mechanism of carbon sequestration in malate biosynthetic pathway was illuminated by analyzing physiological parameters and omic data. These research strategies and idea presented her could provide more understanding of the mechanism of carbon sequestration. Further, they could offer theoretical basis to breed the high-producing strain and optimize fermentation process.