Optimization of Pinocembrin Biosynthesis in Saccharomyces cerevisiae
Journal article, 2023

The flavonoid pinocembrin and its derivatives have gained increasing interest for their benefits on human health. While pinocembrin and its derivatives can be produced in engineered Saccharomyces cerevisiae, yields remain low. Here, we describe novel strategies for improved de novo biosynthesis of pinocembrin from glucose based on overcoming existing limitations in S. cerevisiae. First, we identified cinnamic acid as an inhibitor of pinocembrin synthesis. Second, by screening for more efficient enzymes and optimizing the expression of downstream genes, we reduced cinnamic acid accumulation. Third, we addressed other limiting factors by boosting the availability of the precursor malonyl-CoA, while eliminating the undesired byproduct 2′,4′,6′-trihydroxy dihydrochalcone. After optimizing cultivation conditions, 80 mg/L pinocembrin was obtained in a shake flask, the highest yield reported for S. cerevisiae. Finally, we demonstrated that pinocembrin-producing strains could be further engineered to generate 25 mg/L chrysin, another interesting flavone. The strains generated in this study will facilitate the production of flavonoids through the pinocembrin biosynthetic pathway.

flavonoids

yeast

tolerance

pathway optimization

byproduct

Author

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

ACS Synthetic Biology

2161-5063 (eISSN)

Vol. 12 1 144-152

Subject Categories

Microbiology

Biocatalysis and Enzyme Technology

Other Industrial Biotechnology

DOI

10.1021/acssynbio.2c00425

PubMed

36534476

More information

Latest update

2/22/2023