P450s在萜类合成方面的合成生物学研究进展 <sup>*</sup>

doi:10.13523/j.cb.2003024

中国生物工程杂志

2020, Vol. 40

Issue (8): 84-96 DOI: 10.13523/j.cb.2003024

综述

P450s在萜类合成方面的合成生物学研究进展 ^*

张玉婷^1,²,李伟国^1,²,梁冬梅^1,²,乔建军^1,²,财音青格乐^1,^2,^**(

)

1 天津大学化工学院系统生物工程教育部重点实验室天津 300072
2 天津化学化工协同创新中心合成生物学平台天津 300072

Research Progress in Synthetic Biology of P450s in Terpenoid Synthesis

ZHANG Yu-ting^1,²,LI Wei-guo^1,²,LIANG Dong-mei^1,²,QIAO Jian-jun^1,²,CAI YIN Qing-ge-le^1,^2,^**(

)

1 Key Laboratory of Systems Bioengineering of Ministry of Education, School of Chemical Engineering and Technology,Tianjin University, Tianjin 300072, China
2 Syn Bio Research Platform, Collaborative Innovation Center of Chemical Science and Engineering, Tianjin University, Tianjin 300072, China

全文: PDF(1184 KB) HTML

摘要：

细胞色素P450氧化酶能够催化一系列具有区域特异性、立体特异性的化学步骤,并参与许多天然产物如萜类化合物、甾醇以及生物碱的合成。萜类化合物是活性天然产物中的一大类化合物,在医药、香料等领域具有重要价值。萜类化合物的生物合成及合成后修饰需要P450s,但是目前已知P450s较低的催化活性极大地限制了萜类生物合成的效率。因此,迫切需要发掘和改造用于萜类生物合成的高活性P450s,以充分实现其巨大的工业应用潜力。综述了萜类代谢中涉及到的P450s家族以及近年来萜类生物合成中P450s的发掘和工程研究进展,重点介绍了合成生物学扩宽P450s在萜类合成应用中的主要策略,提出进一步加速P450s发掘和P450s工程的可行策略,并针对合成生物学技术为今后P450s在萜类合成中的应用提出建议与展望。

关键词： 细胞色素P450; 萜类化合物; P450s发掘; P450s工程; 合成生物学

Abstract:

The cytochrome P450 oxidase can catalyze a series of regiospecific and stereospecific chemical steps and participate in the synthesis of many natural products such as terpenoids, sterols and alkaloids. Terpenoids are a large class of compounds in active natural products and have important value in the fields of medicine and perfume. Terpenoids require P450s for biosynthesis and post-modification, but at present, the lower catalytic activity of known P450s greatly limits the efficiency of terpenoid biosynthesis. Therefore, it’s urgent to discover and modify highly active P450s for terpenoid biosynthesis to fully realize its immense industrial application potentiality. This article reviews the different P450s families in terpene metabolism and recent advances in the discovery and engineering of P450s in terpene biosynthesis. Furthermore, it highlights the main strategies of synthetic biology in broadening the application of P450s in terpene synthesis. Feasible strategies have been proposed to further accelerate the discovery of P450s and P450s engineering, based on synthetic biology technology, this article put forward suggestions and prospects for the future application of P450s in terpenoid synthesis.

Key words: Cytochrome P450 Terpenoids Discovery of P450s Engineering of P450s Synthetic biology

收稿日期: 2020-03-08 出版日期: 2020-09-10

ZTFLH:

Q819

基金资助: * 国家重点研发计划资助项目(2017YFD0201400)

通讯作者: 财音青格乐 E-mail: qinggele@tju.edu.cn

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引用本文:

张玉婷,李伟国,梁冬梅,乔建军,财音青格乐. P450s在萜类合成方面的合成生物学研究进展 ^*[J]. 中国生物工程杂志, 2020, 40(8): 84-96.

ZHANG Yu-ting,LI Wei-guo,LIANG Dong-mei,QIAO Jian-jun,CAI YIN Qing-ge-le. Research Progress in Synthetic Biology of P450s in Terpenoid Synthesis. China Biotechnology, 2020, 40(8): 84-96.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.2003024 或 https://manu60.magtech.com.cn/biotech/CN/Y2020/V40/I8/84

图1 P450s催化循环示意图

图2 萜类生物合成途径示意图

表1 参与萜类及其衍生物合成的植物P450s

表2 萜类代谢中功能表征的P450s的分布

图3 P450s催化萜类合成的主要策略

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