Strategies of Engineering <i>Saccharomyces cerevisiae</i> for High-efficiency Synthesis of Sesquiterpenes

doi:10.13523/j.cb.2110033

China Biotechnology

2022, Vol. 42

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

Orginal Article

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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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

Received: 22 October 2021 Published: 03 March 2022

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Corresponding Authors: Jian-jun QIAO E-mail: jianjunq@tju.edu.cn

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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.

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

Table 1 Engineering strategies of Saccharomyces cerevisiae for the synthesis of different sesquiterpenes

Fig.1 Sesquiterpene biosynthetic pathway in Saccharomyces cerevisiae Key enzymes are shown:PDH-complex, Pyruvate dehydrogenase complex; PDC, Pyruvate decarboxylase; ALD, Acetaldehyde dehydrogenase; ACS, Acetyl-CoA synthase; ERG10, Acetoacetyl-CoA thiolase; HMGS, Hydroxymethylglutaryl-CoA synthase; HMGR, 3-Hydroxy-3-methylglutaryl-CoA reductase; ERG12, Mevalonate kinase; ERG8, Phosphomevalonate kinase; MVD1, Diphosphomevalonate decarboxylase; IDI1, Isopentenyl diphosphate isomerase; ERG20, Farnesyl diphosphate synthase; STS, Sesquiterpene synthase; LPP1, Lipid phosphate phosphatase; DPP1, Diacylglycerol pyrophosphate phosphatase; ERG9, Squalene synthase

Fig.2 Catalytic process of sesquiterpene synthase


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