酶催化在维生素及其衍生物制备中的应用

Application of enzyme catalysis in the preparation of vitamins and their derivatives

酶是一种天然的催化剂,与化学催化剂相比,酶往往具有独特而卓越的催化性能。对酶的挖掘、改造和应用一直是生物工程重要研究方向。随着酶的挖掘和改造技术不断发展进步,酶催化技术在工业上的应用范围也越来越广。在维生素工业生产中,维生素C和维生素B_(12)早已实现发酵法生产,而维生素B_(2)在21世纪初也由化学合成转向发酵法生产。除上述维生素外,其他维生素均主要采用化学路线合成。而在维生素的化学合成路径中,酶催化替代化学催化的案例越来越多,比如维生素B_(3)、维生素B_(5)和维生素D_(3)的合成,以及维生素酯类和糖苷类衍生物的合成。所涉及的酶种类包括酯水解酶、天冬氨酸酶、P450酶和脂肪酶等。本文对酶的筛选和改造方法做了总结,综述了酶催化技术在维生素及其衍生物合成中的应用。随着对酶催化机制的深入理解,化学工程、计算机辅助设计等多学科交叉融合,酶催化技术将在维生素及其他天然产物的合成方面发挥其独特优势。

Enzymes,as a kind of natural catalysts,often have unique and excellent catalytic performance compared with chemical catalysts.The mining,modification and application of enzymes have always been a key research field of bioengineering.With the development of enzymes mining and modification technology,enzymatic catalysis has been widely used in industry.In the production of vitamins,vitamin C and vitamin B_(12) have been produced by fermentation with a long history,and vitamin B_(2) has also been produced by fermentation instead of chemical synthesis since the beginning of this century.In addition to the above vitamins,other vitamins are mainly synthesized by chemical routes.In the chemical process of vitamin synthesis,more and more cases of enzymatic catalysis to replace chemical catalysis have been explored for semi-chemo-based production.For examples:Biological enzymatic resolution instead of chemical chiral resolution in vitamin B_(5) synthesis;Nitrile hydration catalyzed by nitrile hydratase instead of chemical catalyst in the synthesis of vitamin B_(3);The synthesis of active vitamin D_(3)[such as 25(OH)vitamin D_(3)]by P450 enzyme.Furthermore,many vitamin esters or glycoside derivatives are synthesized by lipases or glycosyltransferases.In this article,industrial applications of enzymes in this regard are reviewed,including screening,directed evolution and rational modification of the enzymes.Moreover,the applications of enzymatic catalysis in the synthesis of vitamins are summarized,including vitamin B_(3),vitamin B_(5) and vitamin D_(3).The production of vitamin C is also highlighted because its fermentation process is similar to enzymatic catalysis.We also summarize the synthesis of several vitamin derivatives,mainly including ester derivatives of vitamin A,vitamin C and vitamin E,which are synthesized by lipases,and glycoside derivatives of vitamin C,which are synthesized by glycosyltransferases.Finally,we compare the advantages and disadvantages of chemical synthesis,fermentation and enzymatic catalysis in the production of vitamins.The characteristics and application potential of enzymatic catalysis are summarized.With the in-depth understanding of enzymatic catalysis mechanism,enzymes will play their unique advantages in the synthesis of vitamins and other natural products through integration of chemical engineering,computer aided design and other interdisciplinary knowledges.