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.
flavonoid glycosides
two-enzyme system
promoter engineering
glycosylation
UDP-glucose
Author
Zhiqiang Xiao
Hunan University
Hunan Agricultural Product Processing Institute
Hunan Academy of Agricultural Sciences
Yongtong Wang
Hunan Academy of Agricultural Sciences
Hunan University
Hunan Agricultural Product Processing Institute
Juan Liu
Hunan University
Chalmers, Life Sciences, Systems and Synthetic Biology
Hunan Academy of Agricultural Sciences
Hunan Agricultural Product Processing Institute
Siqi Zhang
Hunan Agricultural Product Processing Institute
Hunan Academy of Agricultural Sciences
Hunan University
Xinjia Tan
Hunan Academy of Agricultural Sciences
Hunan Agricultural Product Processing Institute
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 University
Hunan Academy of Agricultural Sciences
ACS Synthetic Biology
2161-5063 (eISSN)
Vol. 12 9 2740-2749Subject Categories (SSIF 2011)
Food Science
DOI
10.1021/acssynbio.3c00348
PubMed
37566738