1.浙江新和成股份有限公司,浙江 绍兴 312500
2.浙江大学化学工程与生物工程学院生物工程研究所,浙江 杭州 310027
[ "王盼盼(1990—),男,博士。研究方向为维生素类产品的生物合成,长期从事酶改造、酶催化和发酵工艺优化相关研发工作。E-mail:wpan2016@sina.com" ]
[ "于洪巍(1972—),男,博士,教授。长期从事生物催化研究,致力于利用蛋白质工程和代谢工程手段提高化学品的生物合成效率。E-mail:yuhongwei@zju.edu.cn" ]
收稿:2021-07-02,
修回:2021-11-10,
纸质出版:2022-06-30
移动端阅览
王盼盼, 于洪巍. 酶催化在维生素及其衍生物制备中的应用[J]. 合成生物学, 2022, 3(3): 500-515
WANG Panpan, YU Hongwei. Application of enzyme catalysis in the preparation of vitamins and their derivatives[J]. Synthetic Biology Journal, 2022, 3(3): 500-515
王盼盼, 于洪巍. 酶催化在维生素及其衍生物制备中的应用[J]. 合成生物学, 2022, 3(3): 500-515 DOI: 10.12211/2096-8280.2021-070.
WANG Panpan, YU Hongwei. Application of enzyme catalysis in the preparation of vitamins and their derivatives[J]. Synthetic Biology Journal, 2022, 3(3): 500-515 DOI: 10.12211/2096-8280.2021-070.
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.
2
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