黄酮类化合物在食品、医药等领域具有广泛应用。大量研究表明，微生物胞内丙二酰-CoA含量不足，是导致黄酮类化合物产量提升的瓶颈。目前对微生物积累丙二酰-CoA强化黄酮类化合物的研究策略主要依赖于静态调控策略。基于静态调控策略改造的代谢工程菌株，在发酵过程中通常需要添加诱导剂、抗生素，并进行精细的分阶段培养，极大的增加了生产过程的成本。本项目通过转录组学技术系统筛选酿酒酵母中可感应典型黄酮类化合物及其中间产物的反馈启动子，为改造酿酒酵母动态强化积累丙二酰-CoA提供合成生物学元件。利用筛选得到的系列反馈启动子构建黄酮类化合物感应信号放大系统，实现胞内丙二酰-CoA积累与细胞生长相偶联的动态调控模式。本项目的研究结果将系统解析酿酒酵母胞内丙二酰辅酶A的胞内调控过程，并为在真核微生物中建立自发动态调控过程强化以丙二酰辅酶A为前体的目标产物高效合成过程提供理论与技术参考。

Flavonoids have extensive applications in food and pharmaceutical industries. Previous researches showed that the bottleneck for the improvement of flavonoids titer in microorganisms was the limited supply of the malonyl-CoA. Current strategies for enhancing the malonyl-CoA for the flavonoids production mainly depended on the stationary regulation. The stationary regulation based metabolic engineering strains require the additional of inducers and antibiotics, and extraordinary multi-phase fermentation processes, which could significantly increase the cost for the final products. In the current project, we want to screen a series of promoters, which could responded to the different concentration of typical flavonoids and their intermediates, to provide the essential units for the engineering Saccharomyces cerevisiae for the dynamic regulation system. Based on the responsible promoters, we would further establish a series of signal amplification systems, which could be used for the dynamic coupled regulation between intracellular malonyl-CoA concentration and cell growth. The results obtained from the current project could not only systematically demonstrate the intracellular regulation process of malonyl-CoA in S. cerevisiae, but could also provide theoretical and technical references for establishing autonomously dynamic regulation systems with the malonyl-CoA as the precursor.