Production of Triterpene Ginsenoside Compound K in the Non-conventional Yeast <i>Yarrowia lipolytica</i>

Li, Dashuai; Wu, Yufen; Zhang, Chuanbo; Sun, Jie; Zhou, Zhansong; Lu, Wenyu

doi:10.1021/acs.jafc.9b00009

Cited by 64 publications

(49 citation statements)

References 50 publications

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“…In general, increasing copy numbers of the genes involved in the rate-limiting enzymes or ginsenoside biosynthesis in engineered yeast will improve the target compound production. However, the highest copy number of the genes did not always lead to the highest product yield due to the metabolic burden in engineered yeast (Hu et al, 2019;Li et al, 2019). The integration of exogenous DNA into the yeast genome can be obtained through homology-direct recombination (HDR) or non-homologous end joining (NHEJ).…”

Section: Rh2mentioning

confidence: 99%

“…The integration of the synthetic codon optimization of DDS into single-and multi-copy sites of rDNA in the Y. lipolytica genome resulted in a DM production of 7.9 and 17.9 mg/L, respectively. Subsequently, the codon optimization of PPDS, ATR1, and UGT1 from P. ginseng, was also integrated into multi-copy site rDNA of the Y. lipolytica genome leading to the synthesis of PPD and compound K (Li et al, 2019).…”

Section: Enhancing Enzyme Expressionmentioning

confidence: 99%

“…Finally, PPD production could be obtained at 1,436.6 mg/L in fedbatch fermentation (Zhao et al, 2016c). Using the same strategy, engineered Y. lipolytica harboring fusion genes PgPPDS and t46AtCPR1 achieved a conversion rate of 98% of PPD from 111.8 mg/L of DM (Table 1) (Li et al, 2019).…”

Section: Modulation the Expression Of Cyp450smentioning

confidence: 99%

“…S. cerevisiae is a superior to E. coli in production ginsenosides because of its accumulate the sufficient pools of precursors for mevalonic acid (MVA) pathways (Ren et al, 2017). Moreover, compared with the potential cost of yeast-producing ginsenosides (∼US$ 0.5-25 per miligram), the value of ginsenosides extracted from Panax plants is relatively expensive with a current price of US$ 25-57 per miligram, depending on purity and type of ginsenosides (Dai et al, 2014;Wei et al, 2015;Li et al, 2019;Wang et al, 2019). Therefore, the development of the yeast-producing ginsenosides is expected to continuously enlarge for creating an alternative approach instead of extraction from plant source.…”

Section: Introductionmentioning

confidence: 99%

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Recent Advances in the Metabolic Engineering of Yeasts for Ginsenoside Biosynthesis

Chu

Montecillo

Bae

2020

Front. Bioeng. Biotechnol.

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Ginsenosides are a group of glycosylated triterpenes isolated from Panax species. Ginsenosides are promising candidates for the prevention and treatment of cancer as well as food additives. However, owing to a lack of efficient approaches for ginsenoside production from plants and chemical synthesis, ginsenosides may not yet have reached their full potential as medicinal resources. In recent years, an alternative approach for ginsenoside production has been developed using the model yeast Saccharomyces cerevisiae and non-conventional yeasts such as Yarrowia lipolytica and Pichia pastoris. In this review, various metabolic engineering strategies, including heterologous gene expression, balancing, and increasing metabolic flux, and enzyme engineering, have been described as recent advanced engineering techniques for improving ginsenoside production. Furthermore, the usefulness of a systems approach and fermentation strategy has been presented. Finally, the present challenges and future research direction for industrial cell factories have been discussed.

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Section: Rh2mentioning

confidence: 99%

Section: Enhancing Enzyme Expressionmentioning

confidence: 99%

Section: Modulation the Expression Of Cyp450smentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Recent Advances in the Metabolic Engineering of Yeasts for Ginsenoside Biosynthesis

Chu

Montecillo

Bae

2020

Front. Bioeng. Biotechnol.

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“…Gwak et al synthesized CK using tobacco as the host, and the concentration of CK achieved was 1.55-2.64 μg/g CDW [12]. Li et al overexpressed the key genes of the mevalonate (MVA) pathway and the fusion of PPDS-ARR1 in Yarrowia lipolytica, and the CK production in 5-L bioreactor was 161.8 mg/L with fermentation optimization [13].…”

Section: Open Accessmentioning

confidence: 99%

Promotion of compound K production in Saccharomyces cerevisiae by glycerol

et al. 2020

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Background: Ginsenoside compound K (CK), one of the primary active metabolites of protopanaxadiol-type ginsenosides, is produced by the intestinal flora that degrade ginseng saponins and exhibits diverse biological properties such as anticancer, anti-inflammatory, and anti-allergic properties. However, it is less abundant in plants. Therefore, enabling its commercialization by construction of a Saccharomyces cerevisiae cell factory is of considerable significance. Results:We induced overexpression of PGM2, UGP1, and UGT1 genes in WLT-MVA5, and obtained a strain that produces ginsenoside CK. The production of CK at 96 h was 263.94 ± 2.36 mg/L, and the conversion rate from protopanaxadiol (PPD) to ginsenoside CK was 64.23 ± 0.41%. Additionally, it was observed that the addition of glycerol was beneficial to the synthesis of CK. When 20% glucose (C mol) in the YPD medium was replaced by the same C mol glycerol, CK production increased to 384.52 ± 15.23 mg/L, which was 45.68% higher than that in YPD medium, and the PPD conversion rate increased to 77.37 ± 3.37% as well. As we previously observed that ethanol is beneficial to the production of PPD, ethanol and glycerol were fed simultaneously in the 5-L bioreactor fed fermentation, and the CK levels reached 1.70 ± 0.16 g/L. Conclusions:In this study, we constructed an S. cerevisiae cell factory that efficiently produced ginsenoside CK. Glycerol effectively increased the glycosylation efficiency of PPD to ginsenoside CK, guiding higher carbon flow to the synthesis of ginsenosides and effectively improving CK production. CK production attained in a 5-L bioreactor was 1.7 g/L after simultaneous feeding of glycerol and ethanol.

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Highly efficient production of diverse rare ginsenosides using combinatorial biotechnology

Cao

Zhang

et al. 2020

Biotech & Bioengineering

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The rare ginsenosides are recognized as the functionalized molecules after the oral administration of Panax ginseng and its products. The sources of rare ginsenosides are extremely limited because of low ginsenoside contents in wild plants, hindering their application in functional foods and drugs. We developed an effective combinatorial biotechnology approach including tissue culture, immobilization, and hydrolyzation methods. Rh2 and nine other rare ginsenosides were produced by methyl jasmonate‐induced culture of adventitious roots in a 10 L bioreactor associated with enzymatic hydrolysis using six β‐glycosidases and their combination with yields ranging from 5.54 to 32.66 mg L−1. The yield of Rh2 was furthermore increased by 7% by using immobilized BglPm and Bgp1 in optimized pH and temperature conditions, with the highest yield reaching 51.17 mg L−1 (17.06% of protopanaxadiol‐type ginsenosides mixture). Our combinatorial biotechnology method provides a highly efficient approach to acquiring diverse rare ginsenosides, replacing direct extraction from Panax plants, and can also be used to supplement yeast cell factories.

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Production of Triterpene Ginsenoside Compound K in the Non-conventional Yeast Yarrowia lipolytica

Cited by 64 publications

References 50 publications

Recent Advances in the Metabolic Engineering of Yeasts for Ginsenoside Biosynthesis

Recent Advances in the Metabolic Engineering of Yeasts for Ginsenoside Biosynthesis

Promotion of compound K production in Saccharomyces cerevisiae by glycerol

Highly efficient production of diverse rare ginsenosides using combinatorial biotechnology

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