化工进展 ›› 2021, Vol. 40 ›› Issue (3): 1202-1214.DOI: 10.16085/j.issn.1000-6613.2020-2101

• 专栏:绿色生物制造 • 上一篇    下一篇

微生物合成植物天然产物的细胞工厂设计与构建

孙文涛(), 李春()   

  1. 清华大学化学工程系,北京 100084
  • 收稿日期:2020-10-20 出版日期:2021-03-05 发布日期:2021-03-17
  • 通讯作者: 李春
  • 作者简介:孙文涛(1988—),男,博士,研究方向为代谢工程与合成生物学。E-mail:sunwentao2016@126.com
  • 基金资助:
    国家重点研发计划(2018YFA0901800);国家自然科学基金(21736002)

Design and construction of microbial cell factory for biosynthesis of plant natural products

SUN Wentao(), LI Chun()   

  1. Department of Chemical Engineering, Tsinghua University, Beijing 100084, China
  • Received:2020-10-20 Online:2021-03-05 Published:2021-03-17
  • Contact: LI Chun

摘要:

植物天然产物结构多样,具有丰富的生理活性与功能。利用微生物细胞工厂生产来源稀缺、获取难度大的植物天然产物具有经济可行、环境友好等优势。本文系统介绍了萜烯、黄酮以及生物碱的生物合成途径及其关键酶,阐述了差异转录组学、同功酶挖掘等途径解析与重构的方法。指出关键酶改造、途径动态调控、代谢区室化与代谢网络再平衡是增大外源途径代谢通量、抑制副产物合成、降低产物毒性与菌株代谢负担、提高目标产物合成能力的有效策略。提出了解析合成植物天然产物关键酶在微生物中的催化特异性机制、开发外源途径的高效组装方法等进一步提高微生物细胞工厂生产效率的建议。

关键词: 植物天然产物, 微生物细胞工厂, 途经重构, 合成生物学

Abstract:

Plant natural products possess diverse structures, physiological activities and functions. The use of microbial cell factories to produce plant natural products with scarce sources and difficult to obtain has the advantages of economic viability and environmental friendliness. This paper systematically introduces the biosynthetic pathways and key enzymes of terpenes, flavonoids and alkaloids, and expounds the decipher and reconstruction methods of their biosynthesis pathways including transcriptomics and isozyme mining. It is pointed out that enzyme engineering, dynamic control, metabolic compartmentation and metabolic network rebalance are effective strategies to increase the metabolic flux of exogenous pathways, inhibit by-product synthesis, reduce product toxicity and strain metabolic burden, and improve the synthesis ability of target products. Suggestions are put forward to further improve the production efficiency of microbial cell factories, such as analyzing the catalytic specific mechanism of plant enzymes in microorganisms, and developing efficient assembly methods for exogenous pathways.

Key words: plant natural products, microbial cell factories, pathway reconstruction, synthetic biology

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