Systems Metabolic Engineering of Saccharomyces cerevisiae for the High-Level Production of (2S)-Eriodictyol
Journal article, 2024
(2S)-eriodictyol (ERD) is a flavonoid widely found in citrus fruits, vegetables, and important medicinal plants with neuroprotective, cardioprotective, antidiabetic, and anti-obesity effects. However, the microbial synthesis of ERD is limited by complex metabolic pathways and often results in a low production performance. Here, we engineered Saccharomyces cerevisiae by fine-tuning the metabolism of the ERD synthesis pathway. The results showed that the ERD titer was effectively increased, and the intermediate metabolites levels were reduced. First, we successfully reconstructed the de novo synthesis pathway of p-coumaric acid in S. cerevisiae and fine-tuned the metabolic pathway using promoter engineering and terminator engineering for the high-level production of (2S)-naringenin. Subsequently, the synthesis of ERD was achieved by introducing the ThF3 ' H gene from Tricyrtis hirta. Finally, by multiplying the copy number of the ThF3 ' H gene, the production of ERD was further increased, reaching 132.08 mg L-1. Our work emphasizes the importance of regulating the metabolic balance to produce natural products in microbial cell factories.
flavonoid
metabolic engineering
(2S)-eriodictyol
(2S)-naringenin
metabolic balance
Author
Siqi Zhang
Hunan University
Hunan Agricultural Product Processing Institute
Hunan Academy of Agricultural Sciences
Juan Liu
Chalmers, Life Sciences, Systems and Synthetic Biology
Zhiqiang Xiao
Hunan University
Hunan Agricultural Product Processing Institute
Hunan Academy of Agricultural Sciences
Xinjia Tan
Hunan Academy of Agricultural Sciences
Hunan University
Hunan Agricultural Product Processing Institute
Yongtong Wang
Hunan Agricultural Product Processing Institute
Hunan Academy of Agricultural Sciences
Hunan University
Yifei Zhao
Hunan University
Hunan Academy of Agricultural Sciences
Hunan Agricultural Product Processing Institute
Ning Jiang
Hunan Agricultural Product Processing Institute
Hunan University
Hunan Academy of Agricultural Sciences
Yang Shan
Hunan Agricultural Product Processing Institute
Hunan University
Hunan Academy of Agricultural Sciences
Journal of Fungi
2309608X (eISSN)
Vol. 10 2 119Subject Categories
Microbiology
DOI
10.3390/jof10020119
PubMed
38392791