Key Glycosyltransferase Genes of <i>Panax notoginseng</i>: Identification and Engineering Yeast Construction of Rare Ginsenosides

Jiang, Zhouqian; Gao, Haiyun; Liu, Rong; Xia, Meng; Lü, Yun; Wang, Jiadian; Chen, Xianfeng; Zhang, Yifeng; Li, Dan; Tong, Yuru; Liu, Panting; Liu, Yuan; Luo, Yunfeng; Gao, Jie; Yin, Yong; Huang, Lusheng; Gao, Wei

doi:10.1021/acssynbio.2c00094

Cited by 11 publications

(4 citation statements)

References 42 publications

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“…40 A recent investigation demonstrated that PnUGT33, cloned from P. notoginseng, can catalyze glucose-addition reactions at both C-3 and C-20 positions to produce rare and highly polar ginsenosides (Table 2, Figures 3 and 4). 50 Furthermore, in contrast to traditional UGTs, GT95 syn from the UGT71 family is able to catalyze 20(R)-PPD and 20(R)-PPT to produce 20(R)-CK and 20(R)-F 1 , providing robust support for future research on ginsenoside C20-(S) and C20-(R) isomers. 51 Marking a breakthrough, the first UDP-Rha-dependent glycosyltransferase in P. notoginseng, PnUGT94M1, was identified.…”

Section: Astragalus Membranaceusmentioning

confidence: 89%

Progress in Identification of UDP-Glycosyltransferases for Ginsenoside Biosynthesis

Yuan,

Li,

et al. 2024

J. Nat. Prod.

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Ginsenosides, the primary pharmacologically active constituents of the Panax genus, have demonstrated a variety of medicinal properties, including anticardiovascular disease, cytotoxic, antiaging, and antidiabetes effects. However, the low concentration of ginsenosides in plants and the challenges associated with their extraction impede the advancement and application of ginsenosides. Heterologous biosynthesis represents a promising strategy for the targeted production of these natural active compounds. As representative triterpenoids, the biosynthetic pathway of the aglycone skeletons of ginsenosides has been successfully decoded. While the sugar moiety is vital for the structural diversity and pharmacological activity of ginsenosides, the mining of uridine diphosphate-dependent glycosyltransferases (UGTs) involved in ginsenoside biosynthesis has attracted a lot of attention and made great progress in recent years. In this paper, we summarize the identification and functional study of UGTs responsible for ginsenoside synthesis in both plants, such as Panax ginseng and Gynostemma pentaphyllum, and microorganisms including Bacillus subtilis and Saccharomyces cerevisiae. The UGT-related microbial cell factories for large-scale ginsenoside production are also mentioned. Additionally, we delve into strategies for UGT mining, particularly potential rapid screening or identification methods, providing insights and prospects. This review provides insights into the study of other unknown glycosyltransferases as candidate genetic elements for the heterologous biosynthesis of rare ginsenosides.

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Section: Astragalus Membranaceusmentioning

confidence: 89%

Progress in Identification of UDP-Glycosyltransferases for Ginsenoside Biosynthesis

Yuan,

Li,

et al. 2024

J. Nat. Prod.

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“…With the development of high-throughput sequencing technology, plant transcriptomes are being studied more and more extensively, facilitating the mining of biosynthetic pathways of many high-value plant natural products. , Currently, transcriptome sequencing technology combined with bioinformatics analysis is an effective means to mine UGTs. − de Costa et al and Kim et al identified glycosyltransferases Ca UGT73AD1 and Ca UGT73AH1 mediating glycosylation of asiatic acid from the C. asiatica transcriptome, but the UGTs that ultimately generate asiaticoside and madecassoside need to be further investigated. , Asiaticoside and madecassoside share the same sugar chain (glucose–glucose–rhamnose) linking their carboxyl groups .…”

Section: Discussionmentioning

confidence: 99%

Elucidation of the Biosynthesis of Asiaticoside and Its Reconstitution in Yeast

Zhao,

Wei,

et al. 2024

ACS Sustainable Chem. Eng.

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Asiaticoside is a triterpenoid in Centella asiatica with wound healing and anti-inflammatory activities. De novo production of asiaticoside remains incompletely resolved. To determine the asiaticoside biosynthetic pathway, a variety of metabolic engineering modifications were made to achieve a high level of synthesis of asiatic acid in Saccharomyces cerevisiae. Transcriptome analysis of C. asiatica identified 51 glycosyltransferases that are potentially involved in the glycosylation of asiatic acid to form asiaticoside. Functional analysis of these glycosyltransferases revealed that CaUGT73C7 and CaUGT73C8 function in the glucosylation of asiatic acid monoglycoside at the C-28 position and five rhamnose glycosyltransferases convert asiatic acid diglucoside to asiaticoside. To achieve the de novo biosynthesis of asiaticoside in S. cerevisiae, glycoside hydrolase EGH1 that degrades asiaticoside was knocked out and key pathway enzymes were introduced. After a series of metabolic engineering modifications, the de novo biosynthesis of asiaticoside was achieved with a titer of 772.3 μg/L in a 5 L fermenter. This is the first time the complete pathway of asiaticoside has been identified and de novo synthesis in microorganisms. The results provide a valuable reference for the biosynthesis of asiaticoside and other similar triterpenoid saponins.

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“…Unfortunately, the content of ginsenoside F1 is extremely low in Panax herbs and the price of ginsenoside F1 goes high, thus restricting the large-scale application of ginsenoside F1 in medicinal and healthcare industries. Recently, synthetic biology is considered as a sustainable and green solution to get important natural medicines by establishing heterologous synthesis system (Kai et al 2018;Bi et al 2022;Jiang et al 2022). We consider that ginsenoside F1 could also be produced through heterologous expression system with green mode rather than extracted it from the plants of Panax species.…”

Section: Introductionmentioning

confidence: 99%

Constructing a Biosynthetic Pathway of Ginsenoside F1 to Achieve Its Synthesis in Tobacco

Chen,

Lei,

et al. 2023

Preprint

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Ginsenoside F1 has high medicinal values, which is a kind of rare triterpene saponin isolated from Panax plants. The extremely low content of ginsenoside F1 in herbs has limited its research and application in medical field. In this work, we constructed a pathway in tobacco for the biosynthesis of ginsenoside F1 by metabolic engineering. Four enzyme genes (PnDDS, CYP12H, CYP6H and UGT20) isolated from Panax notoginseng were introduced into tobacco. Thus, a biosynthetic pathway for ginsenoside F1 synthesis was artificially constructed in tobacco cells; moreover, the four exogenous genes could be expressed in the roots, stems and leaves of transgenic plants. Consequently, ginsenoside F1 and its precursors were successfully synthesized in the transgenic tobacco, compared with Panax plants, the content of ginsenoside F1 in transgenic tobacco was doubled. Based on these results, a new approach was established to produce rare ginsenoside F1; meanwhile, such strategy could also be employed in plant hosts for the heterologous synthesis of other important or rare natural products.

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Key Glycosyltransferase Genes of Panax notoginseng: Identification and Engineering Yeast Construction of Rare Ginsenosides

Cited by 11 publications

References 42 publications

Progress in Identification of UDP-Glycosyltransferases for Ginsenoside Biosynthesis

Progress in Identification of UDP-Glycosyltransferases for Ginsenoside Biosynthesis

Elucidation of the Biosynthesis of Asiaticoside and Its Reconstitution in Yeast

Constructing a Biosynthetic Pathway of Ginsenoside F1 to Achieve Its Synthesis in Tobacco

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