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.

The reproducible forming-free resistive switching (RS) behavior in rare-earth-oxide Gd2O3 polycrystalline thin film was demonstrated. The characteristic of this forming-free RS was similar to that of other forming-necessary binary RS materials except that its initial resistance starts from not the high resistance state (HRS) but the low resistance state (LRS). An ultrahigh resistance switching ratio from HRS to LRS of about six to seven orders of magnitude was achieved at a bias voltage of 0.6 V. Mechanism analysis indicated that the existence of metallic Gd in the Gd2O3 films plays an important role in the forming-free RS performance. Our work provides a novel material with interesting RS behavior, which is beneficial to deepen our understanding of the origin of RS phenomenon.

Background: Kaempferol is a flavonol with broad bioactivity of anti-oxidant, anti-cancer, anti-diabetic, anti-microbial, cardio-protective and anti-asthma. Microbial synthesis of kaempferol is a promising strategy because of the low content in primary plant source. Methods:In this study, the biosynthesis pathway of kaempferol was constructed in the budding yeast Saccharomyces cerevisiae to produce kaempferol de novo, and several biological measures were taken for high production.Results: Firstly, a high efficient flavonol synthases (FLS) from Populus deltoides was introduced into the biosynthetic pathway of kaempferol. Secondly, a S. cerevisiae recombinant was constructed for de novo synthesis of kaempferol, which generated about 6.97 mg/L kaempferol from glucose. To further promote kaempferol production, the acetyl-CoA biosynthetic pathway was overexpressed and p-coumarate was supplied as substrate, which improved kaempferol titer by about 23 and 120%, respectively. Finally, a fed-batch process was developed for better kaempferol fermentation performance, and the production reached 66.29 mg/L in 40 h. Conclusions:The titer of kaempferol in our engineered yeast is 2.5 times of the highest reported titer. Our study provides a possible strategy to produce kaempferol using microbial cell factory.