摘要
植物三萜化合物是一类具有6个C5异戊二烯单元的高附加值天然化合物,具有抗炎、护肝、抗肿瘤、抗氧化和降血压等重要药理活性。在三萜化合物生物合成过程中,细胞色素P450酶通过引入羟基、羧基、羰基以及环氧基等官能团,为丰富三萜结构的多样性起到了重要的作用。然而,目前P450酶底物催化特异性机制仍不清晰,异源底盘细胞中表达率低、与细胞色素氧化还原酶(CPR)的适配性差限制了其在植物三萜化合物微生物异源合成中的应用。本文系统地介绍了植物三萜化合物的合成途径、P450酶的催化系统组成和催化机制。通过P450酶的理性与非理性的分子改造,P450酶及其CPR的适应性匹配以及关键代谢途径的区室化研究,以期为P450酶在高效合成三萜化合物的应用提供研究思路。
Plant triterpenoids are a large group of value-added natural compounds with six C5isoprene units.Many triterpenoids have pharmacological functions such as anti-inflammation,hepatoprotection,anti-tumor,anti-oxidation,and anti-hypertension.In the biosynthesis of triterpenoids,cytochrome P450 enzymes(P450s)play an important role in enlarging the structural diversity of triterpenoids by introducing hydroxyl,carboxyl,carbonyl and epoxy groups.However,the substrate specificity mechanism of P450s for triterpenoids synthesis is still not clear,and the heterologous expression rates of some P450 genes in heterologous chassis cells are low,and the efficiently transfer electrons between some P450s and CPR is not well,which seriously limits its application in the microbial heterologous synthesis of plant triterpenoids.In this paper,we systematically introduce the synthesis pathway of plant triterpenoids,the catalytic system’s composition and mechanism of P450s,and summarize the rational and irrational molecular modification strategies of P450s,the adaptive matching efficiency between P450s and CPR,rationally compartmentalizer,which provide potential strategies for the application of P450s in the efficient synthesis of triterpenoids.
作者
杨成佳
成旭
胡冰
吕波
李春
YANG Chengjia;CHENG Xu;HU Bing;LU Bo;LI Chun(School of Chemistry and Chemical Engineering,Beijing Institute of Technology,Beijing 100081,China;Department of Chemical Engineering,Tsinghua University,Beijing 100084,China)
出处
《生物加工过程》
CAS
2023年第1期39-49,共11页
Chinese Journal of Bioprocess Engineering
基金
国家重点研发计划(2018YFA0901800)。
关键词
三萜化合物
P450酶
催化机制
催化特异性
CPR适配
triterpenoids
cytochrome P450 enzymes
catalytic mechanism
catalytic specificity
CPR adaptation
作者简介
杨成佳(1993-),女,山西吕梁人,硕士研究生,研究方向:代谢工程与合成生物学;联系人:吕波,研究员,E-mail:lv-b@bit.edu.cn。
