Rosin, a characteristic bioactive compound of the endangered medicinal plant Rhodiola rosea, exhibits diverse pharmacological properties. However, conventional approaches such as chemical synthesis and plant extraction fail to meet the requirements of sustainable development. In this study, we engineered Saccharomyces cerevisiae to construct a glucose-based microbial platform for rosin biosynthesis. First, feedback inhibition in the aromatic amino acid synthesis pathway was alleviated by overexpression of feedback-resistant mutant enzymes and introduction of exogenous isozymes. Concurrently, the phosphoketolase pathway was integrated to enhance erythrose-4-phosphate (E4P) supply, thereby reinforcing aromatic amino acid biosynthesis. The reported cinnamoyl-CoA reductase (CCR) and carboxylic acid reductase (CAR) pathways are both capable of synthesizing cinnamyl alcohol. This study systematically evaluated, these two pathways in S. cerevisiae, achieving de novo biosynthesis of cinnamyl alcohol with shake-flask titers of 0.35 mg/L and 35.51 mg/L, respectively. Subsequently, seven glycosyltransferases (GTs) were screened for cinnamyl alcohol glycosylation, with AtUGT73C5^syn from Arabidopsis thaliana demonstrating the highest catalytic efficiency. By integrating Atugt73c5^syn into the cinnamyl alcohol-producing strain, we achieved de novo biosynthesis of rosin in S. cerevisiae for the first time, which reached a titer of 14.91 mg/L in shake flasks. Further optimization by increasing the copy number of glycosyltransferase and the UDP-glucose supply increased the titer of rosin to 23.54 mg/L. This study establishes a foundational platform for developing S. cerevisiae as a microbial cell factory for high-titer phenylpropanoid glycoside production.

• PMID: 41457548
• DOI full text
• PubMed
• PubTator

Reference Type

English Abstract | Journal Article

Authors

Hao Y, Bai P, Tu L, Yin H, Zhuang Y, Liu T

Primary Lit For

Additional Lit For

Review For