BioChem - DOS

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

Nature communications

Liu, Xiaonan; Cheng, Jian; Zhang, Guanghui; Ding, Wentao; Duan, Lijin; Yang, Jing; Kui, Ling; Cheng, Xiaozhi; Ruan, Jiangxing; Fan, Wei; Chen, Junwen; Long, Guangqiang; Zhao, Yan; Cai, Jing; Wang, Wen; Ma, Yanhe; Dong, Yang; Yang, Shengchao; Jiang, Huifeng

<▼1><P>The flavonoid extract from <I>Erigeron breviscapus</I>, breviscapine, has increasingly been used to treat cardio- and cerebrovascular diseases in China for more than 30 years, and plant supply of <I>E. breviscapus</I> 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-<I>O</I>-glucuronosyltransferase and flavone-6-hydroxylase) from <I>E. breviscapus</I> genome and engineer yeast to produce breviscapine from glucose. After metabolic engineering and optimization of fed-batch fermentation, scutellarin and apigenin-7-<I>O</I>-glucuronide, two major active ingredients of breviscapine, reach to 108 and 185 mg l<SUP>&#x2013;1</SUP>, 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.</P></▼1><▼2><P>Breviscapine is the flavonoid extract from medical plant <I>Erigeron breviscapus</I> for the treatment of cardio- and cerebrovascular disease. Here, the authors identify the key enzymes of the biosynthetic pathway from the plant genome and engineer yeast to produce breviscapine from glucose.</P></▼2>

2018

Nature Publishing Group UK

cc-by

2041-1723

9

1

pp.448

10.1038/s41467-018-02883-z

http://click.ndsl.kr/servlet/OpenAPIDetailView?keyValue=05787966&target=NART&cn=NART79519775

https://www.nature.com/articles/s41467-018-02883-z.pdf