合成生物学 ›› 2022, Vol. 3 ›› Issue (1): 168-183.DOI: 10.12211/2096-8280.2020-082

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微生物细胞工厂合成五环三萜皂苷类化合物

任师超1, 孙秋艳1, 冯旭东1, 李春1,2,3   

  1. 1.北京理工大学化学与化工学院化学工程系,生物化工研究所,医药分子科学与制剂工程工业和信息化部重点实验室,北京 100081
    2.清华大学化学工程系,工业生物催化教育部重点实验室,北京 100084
    3.清华大学,合成与系统生物学研究中心,北京 100084
  • 收稿日期:2021-03-29 修回日期:2021-06-06 出版日期:2022-02-28 发布日期:2022-03-14
  • 通讯作者: 冯旭东
  • 作者简介:任师超(1993—),男,博士研究生。研究方向为合成生物学。E-mail:3120170664@bit.edu.cn|冯旭东(1985—),男,博士,副教授。研究方向为合成生物学。E-mail:xd.feng@bit.edu.cn
  • 基金资助:
    国家重点研发计划(2019YFA0905700);北京市科技新星计划(Z191100001119099)

Biosynthesis of pentacyclic triterpenoid saponins in microbial cell factories

Shichao REN1, Qiuyan SUN1, Xudong FENG1, Chun LI1,2,3   

  1. 1.Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering,Ministry of Industry and Information Technology,Institute of Biochemical Engineering,Department of Chemical Engineering,School of Chemistry and Chemical Engineering,Beijing Institute of Technology,Beijing 100081,China
    2.Key Lab for Industrial Biocatalysis,Ministry of Education,Department of Chemical Engineering,Tsinghua University,Beijing 100084,China
    3.Center for Synthetic and Systems Biology,Tsinghua University,Beijing 100084,China
  • Received:2021-03-29 Revised:2021-06-06 Online:2022-02-28 Published:2022-03-14
  • Contact: Xudong FENG

摘要:

五环三萜皂苷类化合物具有丰富的药理、生理活性,广泛应用于医药、功能食品、保健品、化妆品等领域。目前五环三萜皂苷类化合物的主要获取方式是植物提取,随着合成生物学的发展,利用微生物细胞工厂合成植物天然产物逐渐成为研究热点,它具有生产周期短、工艺简单、环境友好、条件温和等优势,是未来的发展方向。本文结合五环三萜皂苷类化合物的来源及其天然合成途径,综述了典型五环三萜皂苷类化合物的分类、功能活性、结构特点及目前利用微生物细胞工厂合成五环三萜皂苷类化合物的研究现状;分析了部分五环三萜皂苷类化合物合成途径当中的未解析的关键修饰位点及关键酶,并结合已报道的体内、体外研究,对部分未知途径当中催化母核形成苷元的P450酶以及对苷元进行糖基化修饰的糖基转移酶进行了合理预测;结合当前研究现状分析、总结、归纳了利用微生物细胞工厂合成五环三萜皂苷类化合物存在的主要瓶颈,讨论了现阶段工业化生产现状及利用生物合成进行工业化生产所面临的挑战,为高效合成五环三萜皂苷类天然产物的微生物细胞工厂构建提供了理论支持和新思路。

关键词: 合成生物学, 五环三萜皂苷, 微生物细胞工厂, 糖基化修饰, 合成途径

Abstract:

Pentacyclic triterpenoid saponins are important plant natural products, which have five rings composed of six isoprene units. They are widely used in medicine, functional food, health care products, cosmetics and other fields due to their pharmacological and physiological activities. At present, pentacyclic triterpenoid saponins are derived mainly from direct extraction from plants, which has many disadvantages such as the long growth period of plants, competition for farmland, impact on ecological environment and low extraction yield. It is also difficult to obtain pentacyclic triterpenoid saponins through chemical synthesis because of the complexity of their structures, and in the meantime the process using organic reagents and performed under harsh reaction conditions is not environmentally friendly. In recent years, with the development of synthetic biology, A variety of microbial cell factories have been constructed to synthesize plant natural products, which present advantages over their chemical synthesis. In this article, the classification, functional activities, structural characteristics of typical pentacyclic triterpenoids and the progress of their synthesis through microbial cell factories are reviewed based on their plant sources and natural synthesis pathway. The unknown enzymes catalyzing synthesis of the key sites of sapogenins in the pentacyclic triterpenoid saponins synthesis pathway are analyzed. Combined with the reported in vivo and in vitro studies, P450 enzymes and glycosyltransferases that are responsible for the formation of sapogenins and saponins, respectively, in some unidentified pathways are predicted. Based on current research, main bottlenecks for pentacyclic triterpenoid saponins synthesis in microbial cell factories are highlighted, and the situation of industrial production and challenges are discussed, which provide theoretical support and new ideas for constructing microbial cell factories to synthesize pentacyclic triterpenoid saponins more efficiently.

Key words: synthetic biology, pentacyclic triterpenoid saponins, microbial cell factory, glycosylation, synthetic pathway

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