酿酒酵母高效合成萜类化合物的组合调控策略

doi:10.16085/j.issn.1000-6613.2018-1138

摘要/Abstract

摘要：

萜类化合物具有广泛的生理活性与重要的经济价值，利用酿酒酵母进行萜类合成具有低价、高效等优势。然而部分植物源合成萜类的关键酶在酿酒酵母中难表达、产量低，难以工业应用，因此有效的调控策略显得至关重要。本文从萜类化合物在酿酒酵母中的合成途径入手，介绍了关键酶、代谢途径、CRISPR基因编辑系统和人工合成染色体技术4个方面的调控策略在酿酒酵母合成萜类化合物中的应用。阐述了关键酶的筛选、改造，理性与非理性设计，MVA途径、乙酰辅酶A合成途径与亚细胞结构的代谢途径改造的优势。指出了多重调控策略组合调控的方式是实现酿酒酵母高效合成萜类化合物的有效方法。此外，CRISPR基因编辑系统与人工合成染色体技术的快速发展将为酿酒酵母细胞工厂的深入开发与利用提供有力工具。

关键词: 萜类化合物, 酿酒酵母, 组合调控, 代谢工程, 合成生物学

Abstract:

Terpenoids have a wide range of physiological activities and important economic value, and using Saccharomyces cerevisiae for terpenoids synthesis has the advantages of low cost and high efficiency. However, due to the low expression and catalytic efficiency of many key enzymes for terpenoids synthesis in S. cerevisiae, it is difficult to realize industrial applications. The regulation strategies of key enzymes, metabolic pathways, CRISPR gene editing system and synthetic chromosome technology used in S. cerevisiae were elaborated. And the advantages of key enzymes screening, modification, rational and irrational design; regulation strategies for MVA pathway, acetyl-coenzyme A synthesis pathway and subcellular structural modification were summarized. To achieve efficient synthesis of terpenoids in S. cerevisiae, combinatorial regulation strategies should be adopted, and the development of the CRISPR gene editing system and synthetic chromosome technology will provide a powerful tool for the in-depth development and utilization of the S. cerevisiae.

Key words: terpenoids, Saccharomyces cerevisiae, combinatorial regulation, metabolic engineering, synthetic biology

中图分类号:

Q819

常鹏程, 于洋, 王颖, 李春. 酿酒酵母高效合成萜类化合物的组合调控策略[J]. 化工进展, 2019, 38(01): 598-605.

Pengcheng CHANG, Yang YU, Ying WANG, Chun LI. Combinatorial regulation strategies for efficient synthesis of terpenoids in Saccharomyces cerevisiae[J]. Chemical Industry and Engineering Progress, 2019, 38(01): 598-605.

图/表 2

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萜类	合成量	萜类	合成量
牻牛儿醇	36.04^[10]	铁锈醇	10^[14]
椒二醇	50^[11]	β-香树脂醇	138.80^[15]
紫衫二烯	8.7^[12]	甘草次酸	18.9^[16]
次丹参酮二烯	488mg/L^[13]	齐敦果酸	606.9mg/L^[4]

萜类	合成量	萜类	合成量
牻牛儿醇	36.04^[10]	铁锈醇	10^[14]
椒二醇	50^[11]	β-香树脂醇	138.80^[15]
紫衫二烯	8.7^[12]	甘草次酸	18.9^[16]
次丹参酮二烯	488mg/L^[13]	齐敦果酸	606.9mg/L^[4]

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