揭示工程化设计的生物合成体系与细胞整体代谢网络的交互作用及适配性机制是合成生物学研究需要解决的关键科学问题。我们发现微生物固有的翻译后修饰系统在营养代谢及前体供应、合成代谢酶活性调节及代谢流分布调控中可能有重要作用。本项目拟以嵌入赤松素合成途径的工程化大肠杆菌、红霉糖孢菌（红霉素合成菌）及丙酮丁醇梭菌（丁醇生产菌）为研究对象，解析微生物酰基化修饰系统（酶、非酶）及调控信号通路，系统研究合成代谢相关酶酰基化修饰的发生、调节和动态变化，探讨酰基化修饰对代谢酶活性的调节效应机制及其对代谢流分布的影响，阐明酰基CoA积累对微生物合成代谢的多重作用及酰基化反馈调控机理，从酰基CoA平衡及蛋白质翻译后修饰角度揭示微生物内源或嵌入的人工生物合成体系与细胞整体代谢网络的互作机制，通过调节代谢酶酰基化修饰提高合成代谢的适配性及相对代谢流，为建立基于翻译后修饰调控的代谢工程及合成生物学设计提供理论基础。

The key scientific problem to be solved in synthetic biology is to elucidate the crosstalk and adaptive mechanism between the engineered synthetic pathway and the whole cellular metabolic network. Our studies found that the protein post-translational modifications (PTMs) might play a significant role in nutrition metabolism, supply of precursors, regulation of metabolic enzymatic activities and metabolic flux distribution in microorganisms. In this project, we will analyze the enzymatic and non-enzymatic acylation modification and regulatory signaling network in three strains: artificial engineered E. coli for pinosylvin production, Saccharopolyspora erythraea for erythromycin production, and Clostridium acetobutylicum for butanol biosynthesis. We will systematically investigate the occurrence, regulation, and dynamic change of acylation modification on metabolic enzymes in biosynthesis pathway, and their effects on enzymatic activities and metabolic flux distribution. Further, we will elucidate the acylation feedback regulation mechanism on microbial biosynthesis resulted from acyl-CoA accumulation, and also clarify the crosstalk between the artificial engineered pathways and whole cellular metabolic network at the post-translational level of protein acylation modifications. These studies will provide the theoretical principle for novel strategy of metabolic engineering and synthetic biology: ME and SynBio based on the protein acylation modifications for designing and optimizing the artificial engineered pathways through controlling acylation levels of enzymes.