核苷酸生产技术现状及展望

核苷酸的生产方法主要有化学合成法、RNA酶解法、微生物发酵法以及生物催化法。探讨了这些方法的原理和发展及其在工业化生产中的优劣势。化学合成法的路线长、立体选择性差,所用试剂昂贵并有一定毒性,生产成本较高;酶解法能一次得到4种核苷酸的混合物且收率较高,是目前我国核苷酸工业生产所用的主要技术,但其后提取难度大,产品纯度不高;微生物发酵法难以解决细胞通透性的问题;生物催化法是发酵法的延伸,菌体培养和酶催化反应分两步进行,有效地解决了细胞通透性问题,并可以通过偶联不同的基因工程菌株生产多种复杂核苷酸、核苷糖乃至寡聚糖,这在核苷酸工业、医药及糖化学、糖生物学合成工业中是极其重要的一个环节。

Present situation and prospect for production technology of nucleotide

This paper reviews the principle and development of four nucleotides production methods which are chemical synthetic processes, enzymatic hydrolysis of RNA, fermentation and bioconversion. The advantages and disadvantages of the different methods in industrial production are discussed. The chemical synthetic process which requires expensive and poisonous materials,has more procedures and less stereoselectivity.The mixed solution of 5'-nucleotides could be carried out from the enzymatic hydrolysis of RNA with a high yield. It' s the main method for large-scale production of nucleotides in China. But the complication of separation for four nucleotides makes the process long and expensive and it is hard to get pure products. The problem of permeability cannot be solved by fermentation. The bioconversion is the extension of the fermentation which resolves the problem by separating culture and enzymatic reaction step by step. Complex nucleotides, sugar nucleotides and even carbohydrate can be synthesized by coupling metabolically engineered bacteria, which are important for the industry of nucleotide, medicine, glycochemistry and glycobiology.