Improved Enzyme for Efficient Production of Ginsenoside Rg3 from Plant Extracts

Jim Crocker
10th August, 2024

Improved Enzyme for Efficient Production of Ginsenoside Rg3 from Plant Extracts

Image Source: Natural Science News, 2024

Key Findings

  • Researchers at Nanjing Tech University optimized the production of rare ginsenosides Rg3 and Rh2 using genetic engineering and enzyme optimization
  • A mutation in the Bs-YjiCm enzyme significantly increased the yield of Rh2
  • The engineered UGTPg29 enzyme showed improved stability and efficiency, leading to a high yield of Rg3 in a "one-pot" three-enzyme reaction
Ginsenosides, the active compounds in ginseng, are known for their diverse pharmacological effects, including anti-inflammatory and anti-tumor properties. Recent research conducted by Nanjing Tech University has made significant strides in optimizing the biosynthesis of two rare ginsenosides, Rg3 and Rh2, which have shown promise in various medical applications[1]. The study focused on enhancing the production of these rare ginsenosides using a combination of genetic engineering and enzyme optimization. Ginsenosides Rg3 and Rh2 are derivatives of protopanaxadiol (PPD), a major component of ginseng. The enzymes responsible for converting PPD to Rh2 and Rh2 to Rg3 are UDP-glycosyltransferases, specifically the M315F variant of Bs-YjiC (Bs-YjiCm) from Bacillus subtilis and UGTPg29 from Panax ginseng. To increase the yield of Rh2, the researchers introduced a mutation (N178I) in the Bs-YjiCm enzyme. This mutation significantly boosted Rh2 production. Subsequently, they engineered the UGTPg29 enzyme to improve its stability and activity through semi-rational design. The resulting variant (R91M/D184M/A287V/A342L) demonstrated enhanced robustness and efficiency. The researchers then combined the optimized Bs-YjiCm and UGTPg29 enzymes with sucrose synthase AtSuSy from Arabidopsis thaliana in a "one-pot" three-enzyme reaction. This setup allowed for the efficient conversion of PPD to Rg3. By optimizing various factors such as enzyme ratios, pH levels, and concentrations of UDP, sucrose, and DMSO, they achieved a high Rg3 yield of 12.38 mM (9.72 g/L) with a final yield of 68.78% within 24 hours. This study builds on previous research highlighting the therapeutic potential of ginsenosides. For instance, ginsenosides have been shown to suppress hyper-inflammation and modulate immune responses, making them valuable in treating conditions like COVID-19[2]. Additionally, ginsenosides have demonstrated anti-tumor properties by regulating gene expression and apoptosis, particularly involving genes like TP53 and IL-6[3]. Moreover, the study's findings are consistent with earlier research indicating that the pharmacological activities of ginsenosides vary with the cultivation age and harvest season of ginseng[4]. The ability to biosynthesize specific ginsenosides like Rg3 and Rh2 efficiently could lead to more consistent and potent therapeutic applications, bypassing the variability introduced by natural cultivation. In summary, the research from Nanjing Tech University represents a significant advancement in the biosynthesis of rare ginsenosides Rg3 and Rh2. By optimizing enzyme activity and stability, the study has paved the way for large-scale production of these compounds, potentially enhancing their availability for medical use. This work not only supports the therapeutic potential of ginsenosides but also provides a robust framework for future research and development in ginsenoside biosynthesis.

BiotechBiochemPlant Science

References

Main Study

1) Engineering UDP-Glycosyltransferase UGTPg29 for the Efficient Synthesis of Ginsenoside Rg3 from Protopanaxadiol.

Published 9th August, 2024

https://doi.org/10.1007/s12010-024-05009-y

Related Studies

2) Ginseng as a Key Immune Response Modulator in Chinese Medicine: From Antipandemic History to COVID-19 Management.

https://doi.org/10.1142/S0192415X23500027

3) Ginsenosides and Tumors: A Comprehensive and Visualized Analysis of Research Hotspots and Antitumor Mechanisms.

https://doi.org/10.7150/jca.88783

4) Dynamic Changes in Neutral and Acidic Ginsenosides with Different Cultivation Ages and Harvest Seasons: Identification of Chemical Characteristics for Panax ginseng Quality Control.

https://doi.org/10.3390/molecules22050734


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