4.7 Article

Biosynthesis and engineering of kaempferol in Saccharomyces cerevisiae

Journal

MICROBIAL CELL FACTORIES
Volume 16, Issue -, Pages -

Publisher

BMC
DOI: 10.1186/s12934-017-0774-x

Keywords

Kaempferol; Flavonol synthase; Acetyl-CoA; Saccharomyces cerevisiae

Funding

  1. 973 Program [2015CB755704]
  2. Chinese Academy of Sciences
  3. National Natural Science Foundation of China [31670100, 31501041]
  4. Tianjin Research Program of Application Foundation and Advanced Technology [15JCYBJC24200]
  5. University of Macau [SRG2015-00062-ICMS-QRCM]

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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.

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