Engineering yeast for the production of breviscapine by genomic analysis and synthetic biology approaches

Xiaonan Liu, Jian Cheng, Guanghui Zhang, Wentao Ding, Lijin Duan, Jing Yang, Ling Kui, Xiaozhi Cheng, Jiangxing Ruan, Wei Fan, Junwen Chen, Guangqiang Long, Yan Zhao, Jing Cai, Wen Wang, Yanhe Ma, Yang Dong, Shengchao Yang () and Huifeng Jiang ()
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Xiaonan Liu: Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences
Jian Cheng: Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences
Guanghui Zhang: Yunnan Agricultural University
Wentao Ding: Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences
Lijin Duan: Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences
Jing Yang: Yunnan Agricultural University
Ling Kui: University of Chinese Academy of Sciences
Xiaozhi Cheng: Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences
Jiangxing Ruan: Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences
Wei Fan: Yunnan Agricultural University
Junwen Chen: Yunnan Agricultural University
Guangqiang Long: Yunnan Agricultural University
Yan Zhao: Yunnan Agricultural University
Jing Cai: University of Macau
Wen Wang: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences
Yanhe Ma: Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences
Yang Dong: Yunnan Agricultural University
Shengchao Yang: Yunnan Agricultural University
Huifeng Jiang: Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences

Nature Communications, 2018, vol. 9, issue 1, 1-10

Abstract: Abstract The flavonoid extract from Erigeron breviscapus, breviscapine, has increasingly been used to treat cardio- and cerebrovascular diseases in China for more than 30 years, and plant supply of E. breviscapus is becoming insufficient to satisfy the growing market demand. Here we report an alternative strategy for the supply of breviscapine by building a yeast cell factory using synthetic biology. We identify two key enzymes in the biosynthetic pathway (flavonoid-7-O-glucuronosyltransferase and flavone-6-hydroxylase) from E. breviscapus genome and engineer yeast to produce breviscapine from glucose. After metabolic engineering and optimization of fed-batch fermentation, scutellarin and apigenin-7-O-glucuronide, two major active ingredients of breviscapine, reach to 108 and 185 mg l–1, respectively. Our study not only introduces an alternative source of these valuable compounds, but also provides an example of integrating genomics and synthetic biology knowledge for metabolic engineering of natural compounds.

Date: 2018
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DOI: 10.1038/s41467-018-02883-z

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