Systematic Engineering of Saccharomyces cerevisiae Chassis for Efficient Flavonoid-7-O-Disaccharide Biosynthesis
Journal article, 2023

Flavonoids are an essential class of secondary metabolites found in plants and possess various nutritional, medicinal, and agricultural properties. However, the poor water solubility of flavonoid aglycones limits their potential applications. To overcome this issue, glycosylation is a promising approach for improving water solubility and bioavailability. In this study, we constructed a flavonoid-7-O-disaccharide biosynthetic pathway with flavonoid aglycones as substrates in Saccharomyces cerevisiae. Subsequently, through metabolic engineering and promoter strategies, we constructed a UDP-rhamnose regeneration system and optimized the UDP-glucose (UDPG) synthetic pathway. The optimized strain produced up to 131.3 mg/L eriocitrin. After this, the chassis cells were applied to other flavonoids, with substrates such as (2S)-naringenin, (2S)-hesperetin, diosmetin, and (2S)-eriodictyol, which resulted in the synthesis of 179.9 mg/L naringin, 276.6 mg/L hesperidin, 249.0 mg/L neohesperidin, 30.4 mg/L diosmin, and 100.7 mg/L neoeriocitrin. To the best of our knowledge, this is the first report on the biosynthesis of flavonoid-7-O-disaccharide.

glycosylation

promoter engineering

flavonoid glycosides

UDP-glucose

two-enzyme system

Author

Zhiqiang Xiao

Hunan University

Hunan Agricultural Product Processing Institute

Hunan Academy of Agricultural Sciences

Yongtong Wang

Hunan Agricultural Product Processing Institute

Hunan University

Hunan Academy of Agricultural Sciences

Juan Liu

Hunan Academy of Agricultural Sciences

Hunan Agricultural Product Processing Institute

Hunan University

Siqi Zhang

Hunan Agricultural Product Processing Institute

Hunan University

Hunan Academy of Agricultural Sciences

Xinjia Tan

Hunan Agricultural Product Processing Institute

Hunan Academy of Agricultural Sciences

Hunan University

Yifei Zhao

Hunan University

Hunan Agricultural Product Processing Institute

Hunan Academy of Agricultural Sciences

Jiwei Mao

Chalmers, Life Sciences, Systems and Synthetic Biology

Ning Jiang

Hunan Academy of Agricultural Sciences

Hunan Agricultural Product Processing Institute

Jingwen Zhou

Jiangnan University

Yang Shan

Hunan Agricultural Product Processing Institute

Hunan Academy of Agricultural Sciences

Hunan University

ACS Synthetic Biology

2161-5063 (eISSN)

Vol. 12 9 2740-2749

Subject Categories

Food Science

DOI

10.1021/acssynbio.3c00348

PubMed

37566738

More information

Latest update

3/7/2024 9