高效合成倍半萜酿酒酵母的构建策略<sup>*</sup>

doi:10.13523/j.cb.2110033

中国生物工程杂志

2022, Vol. 42

Issue (1/2): 14-25 DOI: 10.13523/j.cb.2110033

工业微生物的设计、改造与应用专题

高效合成倍半萜酿酒酵母的构建策略^*

李然¹,闫晓光¹,李伟国¹,梁冬梅²,财音青格乐¹,乔建军^1,^2,^**(

)

1 天津大学化工学院天津 300072
2 天津大学浙江绍兴研究院绍兴 312300

Strategies of Engineering Saccharomyces cerevisiae for High-efficiency Synthesis of Sesquiterpenes

LI Ran¹,YAN Xiao-guang¹,LI Wei-guo¹,LIANG Dong-mei²,CAI YIN Qing-ge-le¹,QIAO Jian-jun^1,^2,^**(

)

1 School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China
2 Zhejiang Shaoxing Research Institute of Tianjin University, Shaoxing 312300, China

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摘要：

倍半萜是具有较强香气和优良生物活性的萜类化合物,能用于香料、燃料和药物的合成。目前,工业上获取倍半萜的常见方法主要是化学合成以及植物提取。由于常见方法存在产率低、成本高和污染大等不可避免的问题,科研人员开始关注微生物合成倍半萜的相关研究,并且以酿酒酵母为宿主采用代谢工程、酶工程和合成生物学等方法构建了生产各种倍半萜的微生物细胞工厂。介绍和解析了酿酒酵母倍半萜合成途径。围绕乙酰辅酶A的积累、甲羟戊酸途径的强化和改造以及底物竞争途径的抑制三个方面,综述了改造和强化倍半萜合成途径的具体策略和相关实例。概述了近年来关于倍半萜合成酶的挖掘和突变研究进展。最后,针对如何进一步提高酿酒酵母合成倍半萜的效率提出展望与建议。

关键词： 倍半萜; 微生物合成; 酿酒酵母

Abstract:

Sesquiterpenes, which belong to terpenes and have strong fragrance and excellent biological activity, can be used in the synthesis of flavors, biofuels and pharmaceuticals. At present, the common methods of obtaining sesquiterpenes in industry are chemical synthesis and plant extraction. Due to the inevitable problems of low yield, high cost and large pollution in common methods, researchers begin to pay attention to the research of microbial synthesis of sesquiterpenes and used metabolic engineering, enzyme engineering and methods of synthetic biology to construct microbial cell factories of Saccharomyces cerevisiae, which can produce various sesquiterpenes. The sesquiterpene synthesis pathway has been introduced and analyzed in the paper. Focusing on the accumulation of the acetyl-CoA, the improvement and modification of the mevalonate pathway, and the inhibition of competitive pathways, specific strategies and relative examples about the improvement and modification of the sesquiterpene synthesis pathway are reviewed. The research progress about the characterization and mutation of sesquiterpene synthases in recent years is summarized. Finally, the prospect and suggestions are proposed to improve the efficiency of sesquiterpene synthesis in Saccharomyces cerevisiae.

Key words: Sesquiterpene Microbial synthesis Saccharomyces cerevisiae

收稿日期: 2021-10-22 出版日期: 2022-03-03

ZTFLH:

Q819

基金资助: * 国家重点研发计划资助项目(2020YFA0907900)

通讯作者: 乔建军 E-mail: jianjunq@tju.edu.cn

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引用本文:

李然,闫晓光,李伟国,梁冬梅,财音青格乐,乔建军. 高效合成倍半萜酿酒酵母的构建策略^*[J]. 中国生物工程杂志, 2022, 42(1/2): 14-25.

LI Ran,YAN Xiao-guang,LI Wei-guo,LIANG Dong-mei,CAI YIN Qing-ge-le,QIAO Jian-jun. Strategies of Engineering Saccharomyces cerevisiae for High-efficiency Synthesis of Sesquiterpenes. China Biotechnology, 2022, 42(1/2): 14-25.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.2110033 或 https://manu60.magtech.com.cn/biotech/CN/Y2022/V42/I1/2/14

表1 酿酒酵母合成不同倍半萜的改造策略

图1 酿酒酵母中倍半萜的合成途径

图2 倍半萜合成酶催化过程

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