胞磷胆碱的合成策略及研究进展

Advances in the synthesis of cytidine-5'-diphosphate choline

摘要:

胞磷胆碱(cytidine-5'-diphosphate choline, CDP-choline)是磷脂酰胆碱和乙酰胆碱的前体，参与形成细胞膜磷脂双分子层并能够稳定神经递质系统，对脑损伤引起的功能和意识障碍、帕金森病、抑郁症以及青光眼等均有疗效，在临床医学和保健品领域已有应用。胞磷胆碱的化学合成工艺需要采用昂贵且有毒的试剂且会产生各种副产物，工业化生产成本高，正逐步被生物合成法替代。生物合成法分为微生物发酵法和生物催化法两种：微生物发酵法原料相对低廉，但转化率低、分离纯化工艺繁杂；生物催化法分为细胞高密度培养和体外催化合成2个阶段，合成工艺繁杂，但转化率高、提取成本相对较低，是目前工业化生产的主要方式。本文综述了胞磷胆碱的化学合成和生物合成进展，重点介绍胞磷胆碱的代谢途径及生物催化合成工艺，以期为胞磷胆碱的工业化生产提供思路。

Abstract:

Cytidine-5'-diphosphate choline (CDP-choline) plays a crucial role in the formation of the phospholipid bilamolecular layer in cell membranes and the stabilization of the neurotransmitter system, acting as a precursor to phosphatidylcholine and acetylcholine. CDP-choline has been found effective in treating functional and consciousness disorders resulting from brain injury, Parkinson’s disease, depression and glaucoma, and other conditions. As such, CDP-choline is widely utilized in clinical medicine and health care products. The conventional chemical synthesis process of CDP-choline is gradually being replaced by biosynthesis due to the expensive and toxic reagents involved, the production of various by-products, and the high cost of industrial production. Biosynthesis of CDP-choline offers two strategies: microbial fermentation and biocatalysis. Microbial fermentation utilizes inexpensive raw materials but results in a relatively low conversion rate and requires a complex separation and purification process. Biocatalysis, on the other hand, involves two stages: the growth of a living “catalyst” and the conversion of the substrate. Although the synthetic process in biocatalysis is more complex, it offers a higher conversion ratio, and the downstream processing technique for extraction is relatively less costly. Consequently, biocatalysis is currently the primary strategy for the industrial production of CDP-choline. This review aims to summarize the progress made in both chemical synthesis and biosynthesis of CDP-choline, with particular focus on the metabolic pathway and the synthetic processes involved in biocatalysis, in order to provide insights for the industrial production of CDP-choline.