黄酮类化合物是一类重要的植物天然产物，具有多种多样的生物活性，在食品、保健品和医药工业等领域具有广泛的应用前景。尽管研究人员已经在微生物中实现了一些黄酮类化合物的异源合成，但是产量仍然较低。导致微生物异源合成黄酮类化合物效率较低的关键问题，在于目前对于黄酮类化合物关键前体物质丙二酰辅酶A的代谢调控及其对大肠杆菌的细胞生长与关键代谢途径的作用缺乏了解。因此，本项目拟通过基于多位点的反义RNA调控和代谢途径模块化调控策略，实现大肠杆菌中丙二酰辅酶A代谢途径的理解调控。利用具有不同丙二酰辅酶A合成与供给能力的一系列大肠杆菌工程菌株，系统考察丙二酰辅酶A代谢对细胞生长与关键代谢途径的重要影响。在此基础上，通过系统调控大肠杆菌的丙二酰辅酶A代谢过程，优化典型黄酮类化合物的代谢途径，揭示丙二酰辅酶A代谢对黄酮类化合物合成过程的的定量关联。

Flavonoids are a group of important plant natural products that have diverse biological activities. Flavonoids have promising applications in food, health products and pharmaceutical industries. Though researchers achieved the production of different flavonoids in microorganisms, the yield is still very low. Previous researches showed that the bottleneck in improving the yield of flavonoids was caused by the limited understanding on the metabolism of the malonyl-CoA, which is one of the most important precursors of flavonoids. Besides, effect of the malonyl-CoA on the cell growth and main metabolic pathway in Escherichia coli still remains largely unknown. In this project, the malonyl-CoA metabolism was regulated by modular and anti-sense RNA based strategies. By using the strategies, a series of E. coli strains with different ability in malonyl-CoA biosynthesis were obtained. Therefore, effect of the malonyl-CoA on the cell growth and main metabolic pathway could be investigated with these strains. Besides, based on the understanding of the malonyl-CoA metabolism, the metabolic networks of several typical flavonoids would also be optimized to achieve the high efficient production of these chemicals in E. coli.