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Two Ginseng UDP-Glycosyltransferases Synthesize Ginsenoside Rg3 and Rd

TLDR
This work sequenced and assembled the ginseng transcriptome de novo and characterized two UDP-glycosyltransferases (PgUGTs), indicating that these two UGTs are key enzymes for the synthesis of ginsenosides and provide a method for producing specific ginsene biosynthesis through yeast fermentation.
Abstract
Ginseng is a medicinal herb that requires cultivation under shade conditions, typically for 4–6 years, before harvesting. The principal components of ginseng are ginsenosides, glycosylated tetracyclic terpenes. Dammarene-type ginsenosides are classified into two groups, protopanaxadiol (PPD) and protopanaxatriol (PPT), based on their hydroxylation patterns, and further diverge to diverse ginsenosides through differential glycosylation. Three early enzymes, dammarenediol-II synthase (DS) and two P450 enzymes, protopanaxadiol synthase (PPDS) and protopanaxatriol synthase (PPTS), have been reported, but glycosyltransferases that are necessary to synthesize specific ginsenosides have not yet been fully identified. To discover glycosyltransferases responsible for ginsenoside biosynthesis, we sequenced and assembled the ginseng transcriptome de novo and characterized two UDP-glycosyltransferases (PgUGTs): PgUGT74AE2 and PgUGT94Q2. PgUGT74AE2 transfers a glucose moiety from UDP-glucose (UDP-Glc) to the C3 hydroxyl groups of PPD and compound K to form Rh ₂ and F2, respectively, whereas PgUGT94Q2 transfers a glucose moiety from UDP-Glc to Rh ₂ and F2 to form Rg ₃ and Rd, respectively. Introduction of the two UGT genes into yeast together with PgDS and PgPPDS resulted in the de novo production of Rg ₃. Our results indicate that these two UGTs are key enzymes for the synthesis of ginsenosides and provide a method for producing specific ginsenosides through yeast fermentation.

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Biosynthesis and biotechnological production of ginsenosides

TL;DR: This review updates the conserved and diversified pathway/enzyme biosynthesizing ginsenosides which have been presented and highlights recent milestone works on functional characterization of key genes dedicated to the production of gINSenosides, and their application in engineering plants and yeast cells for large-scale production.
Journal ArticleDOI

P450s and UGTs: Key Players in the Structural Diversity of Triterpenoid Saponins

TL;DR: This review summarizes the recent progress in gene discovery and elucidates the biochemical functions of biosynthetic enzymes in triterpenoid saponin biosynthesis, with special focus on key players in generating the structural diversity of triter Penoids, cytochrome P450 monooxygenases (P450s) and the UDP-dependent glycosyltransferases (UGTs).
Journal ArticleDOI

Plant secondary metabolism linked glycosyltransferases: An update on expanding knowledge and scopes

TL;DR: The multiple advantages of glycosylation in plant secondary metabolomics highlight the increasing significance of the GTs, and in near future, the enzyme superfamily may serve as promising path for progress in expanding drug targets for pharmacophore discovery and development.
Journal ArticleDOI

Characterization of Panax ginseng UDP-Glycosyltransferases Catalyzing Protopanaxatriol and Biosyntheses of Bioactive Ginsenosides F1 and Rh1 in Metabolically Engineered Yeasts

TL;DR: It is shown that UGTPg1, which has been demonstrated to regio-specifically glycosylate the C20-OH of PPD, also specifically glycosYLates the C 20- OH of PPT to produce bioactive ginsenoside F1, and a sound manufacturing approach for bioactive PPT-type ginsenoides in yeast via synthetic biology strategies is provided.
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