Biosynthesis and engineering of kaempferol in Saccharomyces cerevisiae

Microb Cell Fact. 2017 Sep 26;16(1):165. doi: 10.1186/s12934-017-0774-x.

Abstract

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.

Keywords: Acetyl-CoA; Flavonol synthase; Kaempferol; Saccharomyces cerevisiae.

MeSH terms

  • Biosynthetic Pathways
  • Fermentation
  • Glucose / metabolism
  • Kaempferols / biosynthesis*
  • Metabolic Engineering
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism*

Substances

  • Kaempferols
  • kaempferol
  • Glucose