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

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.