Pathway elucidation of bioactive rhamnosylated ginsenosides in Panax ginseng and their de novo high-level production by engineered Saccharomyces cerevisiae.

Chaojing Li, Xing Yan, Zhenzhen Xu, Yan Wang, Xiao Shen, Lei Zhang, Zhihua Zhou, Pingping Wang

Communications biology 2022 Aug 02

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Rg2 and Re are both rhamnose-containing ginsenosides isolated exclusively from Panax plants, which exhibit broad spectrum of pharmacological activities. However, limitations of current plant-relied manufacturing methods have largely hampered their medical applications. Here, we report elucidation of the complete biosynthetic pathway of these two ginsenosides by the identification of a rhamnosyltransferase PgURT94 from Panax ginseng. We then achieve de novo bio-production of Rg2 and Re from glucose by reconstituting their biosynthetic pathways in yeast. Through stepwise strain engineering and fed-batch fermentation, the maximum yield of Rg2 and Re reach 1.3 and 3.6 g/L, respectively. Our work completes the identification of the last missing enzyme for Rg2 and Re biosynthesis and achieves their high-level production by engineered yeasts. Once scaled, this microbial biosynthesis platform will enable a robust and stable supply of Rg2 and Re and facilitate their food and medical applications. © 2022. The Author(s).

Citation

Chaojing Li, Xing Yan, Zhenzhen Xu, Yan Wang, Xiao Shen, Lei Zhang, Zhihua Zhou, Pingping Wang. Pathway elucidation of bioactive rhamnosylated ginsenosides in Panax ginseng and their de novo high-level production by engineered Saccharomyces cerevisiae. Communications biology. 2022 Aug 02;5(1):775