Engineering yeast for the production of breviscapine by genomic analysis and synthetic biology approaches.
Engineering yeast for the production of breviscapine by genomic analysis and synthetic biology approaches.
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通过基因组分析和合成生物学方法对酵母进行工程改造，用于生产灯盏花素。
DOI：
10.1038/s41467-018-02883-z
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发表时间：
2018-01-31
影响因子：
16.6
通讯作者：
Jiang H
中科院分区：
文献类型：
--
作者：
Liu X;Cheng J;Zhang G;Ding W;Duan L;Yang J;Kui L;Cheng X;Ruan J;Fan W;Chen J;Long G;Zhao Y;Cai J;Wang W;Ma Y;Dong Y;Yang S;Jiang H
灯盏细辛黄酮类提取物在我国已被越来越多地用于心脑血管疾病的治疗，但其植物来源却不多。灯盏花素已不足以满足日益增长的市场需求。在这里，我们报告了另一种策略，通过建立一个酵母细胞工厂，利用合成生物学的灯盏花素供应。我们鉴定了E.灯盏花素基因组和工程酵母从葡萄糖生产灯盏花素。经过代谢工程和补料分批发酵的优化，灯盏花素的两个主要活性成分野黄芩苷和芹菜素-7-O-葡萄糖醛酸苷，分别达到108和185 mg l-1。我们的研究不仅介绍了这些有价值的化合物的替代来源，但也提供了一个例子，整合基因组学和合成生物学知识的天然化合物的代谢工程。灯盏花素是从药用植物灯盏花中提取的黄酮类化合物，用于治疗心脑血管疾病。在这里，作者从植物基因组中识别出生物合成途径的关键酶，并设计酵母从葡萄糖中生产灯盏花素。
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. Breviscapine is the flavonoid extract from medical plant Erigeron breviscapus 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.
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在面包酵母中生产人参皂苷苷元
影响因子：
4.6
作者：
Dai Z;Wang B;Liu Y;Shi M;Wang D;Zhang X;Liu T;Huang L;Zhang X
通讯作者：
Zhang X
影响因子：
48
作者：
Gibson, Daniel G.;Young, Lei;Smith, Hamilton O.
通讯作者：
Smith, Hamilton O.
影响因子：
12.3
作者：
Haas, Brian J.;Salzberg, Steven L.;Zhu, Wei;Pertea, Mihaela;Allen, Jonathan E.;Orvis, Joshua;White, Owen;Buell, C. Robin;Wortman, Jennifer R.
通讯作者：
Wortman, Jennifer R.
DOI：
10.1126/science.aac9373
发表时间：
2015-09-04
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Galanie S;Thodey K;Trenchard IJ;Filsinger Interrante M;Smolke CD
通讯作者：
Smolke CD
影响因子：
2.8
作者：
Lee, Hyejin;Kim, Bong Gyu;Ahn, Joong-Hoon
通讯作者：
Ahn, Joong-Hoon