Optimizing yeast for high-level production of kaempferol and quercetin
Journal article, 2023

BACKGROUND: Two 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. RESULTS: In 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. CONCLUSIONS: De 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.

Yeast

Kaempferol

Flavonoids

Quercetin

Author

Musa Tartik

Chalmers, Life Sciences, Systems and Synthetic Biology

Bingöl University

Juan Liu

Chalmers, Life Sciences, Systems and Synthetic Biology

Marta Tous Mohedano

Chalmers, Life Sciences, Systems and Synthetic Biology

Jiwei Mao

Chalmers, Life Sciences, Systems and Synthetic Biology

Yun Chen

Chalmers, Life Sciences, Systems and Synthetic Biology

Microbial Cell Factories

14752859 (eISSN)

Vol. 22 1 74

Bioinformatics Services for Data-Driven Design of Cell Factories and Communities (DD-DeCaF)

European Commission (EC) (EC/H2020/686070), 2016-03-01 -- 2020-02-28.

Systems metabolic engineering of yeast for production of flavonoids

Novo Nordisk Foundation (NNF18OC0034844), 2019-01-01 -- 2021-12-31.

Increasing oxygen utilisation in biotechnological processes

Novo Nordisk Foundation (NNF22OC0079873), 2023-01-01 -- 2025-12-31.

Subject Categories

Microbiology

Plant Biotechnology

Biocatalysis and Enzyme Technology

Other Industrial Biotechnology

DOI

10.1186/s12934-023-02084-4

PubMed

37076829

Related datasets

Additional file 2 of Optimizing yeast for high-level production of kaempferol and quercetin [dataset]

DOI: 10.6084/m9.figshare.22662441

More information

Latest update

9/21/2023