萜烯生物合成中关键酶的研究进展<sup>*</sup>

doi:10.13523/j.cb.2102032

中国生物工程杂志

2021, Vol. 41

Issue (6): 60-70 DOI: 10.13523/j.cb.2102032

综述

萜烯生物合成中关键酶的研究进展^*

苗轶男¹,李敬知¹,王帅¹,李春^1,²,王颖^1,^**(

)

1 北京理工大学医药分子科学与制剂工程工信部重点实验室化学与化工学院生物化工研究所北京 100081
2 清华大学化学工程系北京 100084

Research Progress of Key Enzymes in Terpene Biosynthesis

MIAO Yi-nan¹,LI Jing-zhi¹,WANG Shuai¹,LI Chun^1,²,WANG Ying^1,^**(

)

1 Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Ministry of Industry and Information Technology, Institute of Biochemical Engineering, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 102488, China
2 Department of Chemical Engineering, Tsinghua University, Beijing 100084, China

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摘要：

萜烯类化合物是一类高度多样化的天然产物,具有抗肿瘤、抗氧化及免疫调节等生理活性,因此被广泛应用于医药健康、食品、化妆品领域。然而,直接从自然资源中获取萜烯类化合物效率低、成本高,且往往对生态环境产生不利影响,不能实现绿色可持续生产。微生物合成萜烯类化合物近年来备受关注,研究人员从合成途径的构建与调控、关键酶的理性及半理性改造、发酵工艺优化等多个方面进行了探究,取得了丰硕的成果。其中,合成途径中关键酶的催化效率是影响微生物生产萜烯类化合物的重要因素。针对关键酶的研究对于提高微生物合成萜烯类化合物的能力,推动该类天然产物微生物生产的大规模应用具有重要意义。对萜烯类化合物合成途径中的3-羟基-3-甲基戊二酰辅酶A还原酶(HMGR)、1-脱氧-D-木酮糖-5-磷酸合酶(DXS)、异戊二烯基二磷酸合成酶(IDS)和萜烯合酶(TPS)4种关键酶的研究进行了综述,并总结讨论了如何通过代谢工程和蛋白质工程手段以及合成生物学技术调节关键酶的催化活性,提高微生物合成萜烯类化合物的效率,对未来利用微生物合成萜烯类化合物的发展进行了展望。

关键词： 萜烯类化合物; 关键酶; 代谢工程; 蛋白质工程; 生物合成

Abstract:

Terpenes are a large class of highly diverse natural products with various physiological activities such as anti-tumor, anti-oxidation and immune regulation. Therefore, they are widely used in the fields of medicine and health, food, cosmetics, and biofuels. However, obtaining terpene compounds directly from natural resources is low efficient, costly, and often has an adverse impact on the ecological environment, making it impossible to achieve green and sustainable production. Microbial synthesis of terpenes has attracted much attention in recent years. Researchers have conducted explorations from the construction and regulation of synthetic pathways, protein engineering, and fermentation process optimization, and have obtained fruitful results. Among them, the efficiency of key enzymes in the synthetic pathway plays an important role in the microbial production of terpenes. Research on key enzymes is of great significance for improving the ability of microorganisms to synthesize terpenes and thus accelerating the large-scale application of microbial production of such natural products. Here, four key enzymes in the synthetic pathway of terpenes including 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), 1-deoxy-D-xylulose-5-phosphate synthase (DXS), isoprenyl diphosphate synthase (IDS), and terpene synthase (TPS) were introduced. The regulation of catalytic activities of key enzymes via metabolic engineering, protein engineering and synthetic biology to improve the efficiency of microbial synthesis of terpenes as well as the prospects of using microorganisms to synthesize terpenes were also reviewed.

Key words: Terpenes Key enzymes Metabolic engineering Protein engineering Biosynthesis

收稿日期: 2021-02-24 出版日期: 2021-07-06

ZTFLH:

Q819

基金资助: * 国家重点研发计划(2019YFA0905700);国家自然科学基金(22078020)

通讯作者: 王颖 E-mail: wy2015@bit.edu.cn

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引用本文:

苗轶男,李敬知,王帅,李春,王颖. 萜烯生物合成中关键酶的研究进展^*[J]. 中国生物工程杂志, 2021, 41(6): 60-70.

MIAO Yi-nan,LI Jing-zhi,WANG Shuai,LI Chun,WANG Ying. Research Progress of Key Enzymes in Terpene Biosynthesis. China Biotechnology, 2021, 41(6): 60-70.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.2102032 或 https://manu60.magtech.com.cn/biotech/CN/Y2021/V41/I6/60

图1 萜烯类化合物的生物合成途径

表1 萜烯生物合成中的关键酶

图2 反式(左)和顺式(右)IDS的反应途径

表2 萜烯化合物合成中的关键酶及调控策略

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