Systems Metabolic Engineering of <i>Saccharomyces cerevisiae</i> for the High-Level Production of (2<i>S</i>)-Eriodictyol
Siqi Zhang | Juan Liu | Zhiqiang Xiao | Xinjia Tan | Yongtong Wang | Yifei Zhao | Ning Jiang | Yang Shan
(2<i>S</i>)-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 <i>Saccharomyces cerevisiae</i> 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 <i>p</i>-coumaric acid in <i>S. cerevisiae</i> and fine-tuned the metabolic pathway using promoter engineering and terminator engineering for the high-level production of (2<i>S</i>)-naringenin. Subsequently, the synthesis of ERD was achieved by introducing the <i>ThF3</i>′<i>H</i> gene from <i>Tricyrtis hirta</i>. Finally, by multiplying the copy number of the <i>ThF3</i>′<i>H</i> gene, the production of ERD was further increased, reaching 132.08 mg L<sup>−1</sup>. Our work emphasizes the importance of regulating the metabolic balance to produce natural products in microbial cell factories.
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