Mining of UDP‐glucosyltrfansferases in licorice for controllable glycosylation of pentacyclic triterpenoids

Zhang, Liang; Ren, Shi‐Chao; Liu, Xiaofei; Liu, Xiaochen; Guo, Fang; Sun, Wentao; Feng, Xudong; Li, Chun

doi:10.1002/bit.27518

Cited by 27 publications

(40 citation statements)

References 42 publications

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“…Although systematic metabolic engineering strategies have been employed in the present study, the production of GA and GAMG was still much lower than other triterpenoids (include GA) reported previously ( Zhu et al, 2017 ; Zhuang et al, 2017 ; Wang C. et al, 2019 ; Zhang et al, 2020 ). The discrepancy in GA production might result from the use of yeast strains with different genetic backgrounds.…”

Section: Discussionmentioning

confidence: 64%

De Novo Production of Glycyrrhetic Acid 3-O-mono-β-D-glucuronide in Saccharomyces cerevisiae

Huang

Jiang

Ren

et al. 2021

Front. Bioeng. Biotechnol.

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Glycyrrhetic acid 3-O-mono-β-D-glucuronide (GAMG) is a rare compound in licorice and its short supply limits the wide applications in the pharmaceutical, cosmetic, and food industries. In this study, de novo biosynthesis of GAMG was achieved in engineered Saccharomyces cerevisiae strains based on the CRISPR/Cas9 genome editing technology. The introduction of GAMG biosynthetic pathway resulted in the construction of a GAMG-producing yeast strain for the first time. Through optimizing the biosynthetic pathway, improving the folding and catalysis microenvironment for cytochrome P450 enzymes (CYPs), enhancing the supply of UDP-glucuronic acid (UDP-GlcA), preventing product degradation, and optimizing the fermentation conditions, the production of GAMG was increased from 0.02 μg/L to 92.00 μg/L in shake flasks (4,200-fold), and the conversion rate of glycyrrhetic acid (GA) to GAMG was higher than 56%. The engineered yeast strains provide an alternative approach for the production of glycosylated triterpenoids.

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Section: Discussionmentioning

confidence: 64%

De Novo Production of Glycyrrhetic Acid 3-O-mono-β-D-glucuronide in Saccharomyces cerevisiae

Huang

Jiang

Ren

et al. 2021

Front. Bioeng. Biotechnol.

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“…Glycosyltransferase activity also affected glycoside compound production . In our study, Ugt73c6 and Ugt73b2, two glycosyltransferases, showed different catalytic abilities, with Ugt73C6 having a stronger catalytic ability in producing naringenin-7-O-glucoside from (2 S )-naringenin.…”

Section: Discussionmentioning

confidence: 65%

Glycosylation Modification Enhances (2S)-Naringenin Production in Saccharomyces cerevisiae

Lyv

et al. 2022

ACS Synth. Biol.

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(2S)-Naringenin is an important flavonoid precursor, with multiple nutritional and pharmacological activities. Both (2S)-naringenin and other flavonoid production are hindered by poor water solubility and inhibited cell growth. To address this, we increased solubility and improved cell growth by partially glycosylating (2S)-naringenin to naringenin-7-O-glucoside, which facilitated increased extracellular secretion, by knocking out endogenous glycosyl hydrolase genes, EXG1 and SPR1, and expressing the glycosyltransferase gene (UGT733C6). Naringenin-7-O-glucoside synthesis was further improved by optimizing UDP-glucose and shikimate pathways. Then, hydrochloric acid was used to hydrolyze naringenin-7-O-glucoside to (2S)-naringenin outside the cell. Thus, our optimized Saccharomyces cerevisiae strain E32T19 produced 1184.1 mg/L (2S)-naringenin, a 7.9-fold increase on the starting strain. Therefore. we propose that glycosylation modification is a useful strategy for the efficient heterologous biosynthesis of (2S)-naringenin in S. cerevisiae.

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“…UGT73C11, 51,52 UGT73C33 and UGT73F24, 53 which had been reported to show activity toward pentacyclic triterpenoids, were first tested in vitro for the C-28 glucosylation of CE and/or OA. Unfortunately, as shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Sustainable production of rare oleanane-type ginsenoside Ro with an artificial glycosylation pathway in Saccharomyces cerevisiae

et al. 2022

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Mining of UDP‐glucosyltrfansferases in licorice for controllable glycosylation of pentacyclic triterpenoids

Cited by 27 publications

References 42 publications

De Novo Production of Glycyrrhetic Acid 3-O-mono-β-D-glucuronide in Saccharomyces cerevisiae

De Novo Production of Glycyrrhetic Acid 3-O-mono-β-D-glucuronide in Saccharomyces cerevisiae

Glycosylation Modification Enhances (2S)-Naringenin Production in Saccharomyces cerevisiae

Sustainable production of rare oleanane-type ginsenoside Ro with an artificial glycosylation pathway in Saccharomyces cerevisiae

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