国际学术期刊《自然通讯》1月31日在线发表中国合成生物学首次实现灯盏花素人工细胞全合成的最新研究成果。灯盏花素合成技术有望将灯盏花(E. breviscapus)素从种植提取转为可持续工业化生产，成本数量级下降，为中药现代化提供新模式。

灯盏花在云南民间用于治疗瘫痪已有上千年历史，灯盏花素为以灯盏乙素为主含少量灯盏甲素的混合物，具有扩张脑血管、降低脑血管阻力、增加脑血流量、改善微循环、对抗血小板聚集等作用，由于临床效果显著，灯盏花素被列为全国中医医院急诊科治疗心脑血管疾病的必备中成药。

灯盏花|来源：百度图片

中国科学院天津工业生物技术研究所与云南农业大学灯盏花团队合作，成功从灯盏花基因组中获得灯盏花素合成途径中的关键基因，并实现了灯盏乙素、灯盏甲素的全合成。

Figure 1. Proposed pathway for breviscapine biosynthesis inE. breviscapusand construction of the apigenin-7-O-glucuronide producing platform strain.

Figure 2. P450 enzymes screening and functional identification.

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

Nature Communications(IF12.124)Pub Date:2018-01-31, DOI:10.1038/s41467-018-02883-z

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, Huifeng Jiang

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.