大肠杆菌乙酰辅酶A代谢调控及其应用研究进展

利用生物法合成生物基化学品具有高效、绿色、可持续发展等优势。乙酰辅酶A作为细胞内物质代谢的重要中间产物，是利用生物转化法合成许多生物基化学品的重要前体，在微生物碳代谢过程中发挥着枢纽作用。本文综述了大肠杆菌乙酰辅酶A的合成、代谢调控策略及其重要应用，重点总结了乙酰辅酶A的合成途径及近期发展的提高乙酰辅酶A胞内通量的代谢调控策略，包括乙酸途径的代谢调控、丙酮酸合成乙酰辅酶A途径的代谢调控、中心碳代谢途径的代谢调控、β氧化合成乙酰辅酶A途径的代谢调控和乙酰辅酶A合成新途径的发掘，进一步展望了提高乙酰辅酶A供给的策略，利用基因组编辑技术构建合成乙酰辅酶A为前体化学品细胞工厂的方法。

Advances in acetyl coenzyme A metabolic engineering with Escherichia coli

Biosynthesis of chemicals has the advantages of high efficiency, green and sustainable development. Acetyl coenzyme A, as an important intermediate of cellular metabolism in cells, is an important precursor for the synthesis of many biochemicals, and has played a vital role in the process of microbial carbon metabolism. Here we reviewed the synthesis and strategies of metabolic regulation of acetyl coenzyme A in Escherichia coli and its important applications. We also summarized the synthesis pathway of acetyl coenzyme A and the recent development of metabolic regulation strategies to increase the intracellular metabolic flux of acetyl coenzyme A production, these including metabolic regulation of the acetyl coenzyme A synthesized by acetic acid and pyruvate, metabolic regulation of the central carbon metabolic pathway and acetyl coenzyme A synthesized by beta oxidation pathway, and discovery of new pathways for acetyl coenzyme A synthesis. Finally, we prospected the feasible strategies of increasing acetyl coenzyme A supply and discussed methods of constructing cell factories for synthesizing acetyl coenzyme A as precursor chemicals by genome editing technology.