Optimizing yeast for high-level production of kaempferol and quercetin

Microbial Cell Factories

卷:22

Research

Juan Liu¹  Jiwei Mao¹  Marta Tous Mohedano¹  Yun Chen¹  Musa Tartik² 

[1] Department of Life Sciences, Chalmers University of Technology, Kemivägen 10, SE-412 96, Gothenburg, Sweden;

[2] Department of Molecular Biology and Genetics, Faculty of Arts and Sciences, Bingol University, 12000, Bingol, Turkey;Department of Life Sciences, Chalmers University of Technology, Kemivägen 10, SE-412 96, Gothenburg, Sweden;

关键词: Yeast;    Flavonoids;    Kaempferol;    Quercetin;   

DOI  :  10.1186/s12934-023-02084-4

 received in 2023-03-11, accepted in 2023-04-09,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundTwo important flavonoids, kaempferol and quercetin possess remarkably potent biological impacts on human health. However, their structural complexity and low abundance in nature make both bulk chemical synthesis and extraction from native plants difficult. Therefore microbial production via heterologous expression of plant enzymes can be a safe and sustainable route for their production. Despite several attempts reported in microbial hosts, the production levels of kaempferol and quercetin still stay far behind compared to many other microbial-produced flavonoids.ResultsIn this study, Saccharomyces cerevisiae was engineered for high production of kaempferol and quercetin in minimal media from glucose. First, the kaempferol biosynthetic pathway was reconstructed via screening various F3H and FLS enzymes. In addition, we demonstrated that amplification of the rate-limiting enzyme AtFLS could reduce the dihydrokaempferol accumulation and improve kaempferol production. Increasing the availability of precursor malonyl-CoA further improved the production of kaempferol and quercetin. Furthermore, the highest amount of 956 mg L− 1 of kaempferol and 930 mg L− 1 of quercetin in yeast was reached in fed-batch fermentations.ConclusionsDe novo biosynthesis of kaempferol and quercetin in yeast was improved through increasing the upstream naringenin biosynthesis and debugging the flux-limiting enzymes together with fed-batch fermentations, up to gram per liter level. Our work provides a promising platform for sustainable and scalable production of kaempferol, quercetin and compounds derived thereof.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

40507_2023_167_Article_IEq456.gif

13638_2023_2232_Article_IEq44.gif

40507_2023_167_Article_IEq451.gif

Fig. 4

13068_2023_2316_Article_IEq2.gif

Fig. 5

Fig. 4