De Novo Production of Glycyrrhetic Acid 3-O-mono-β-D-glucuronide in Saccharomyces cerevisiae
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 th...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:b968d1021b874823a62e52acb421dac02021-11-30T13:32:53ZDe Novo Production of Glycyrrhetic Acid 3-O-mono-β-D-glucuronide in Saccharomyces cerevisiae2296-418510.3389/fbioe.2021.709120https://doaj.org/article/b968d1021b874823a62e52acb421dac02021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fbioe.2021.709120/fullhttps://doaj.org/toc/2296-4185Glycyrrhetic 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.Ying HuangDan JiangGuangxi RenYan YinYifan SunTengfei LiuChunsheng LiuFrontiers Media S.A.articleglycyrrhetic acid 3-O-mono-β-D-glucuronide (GAMG)Saccharomyces cerevisiaecytochrome P450 enzymes (CYPs)CRISPR/Cas9metabolic engineeringBiotechnologyTP248.13-248.65ENFrontiers in Bioengineering and Biotechnology, Vol 9 (2021) |
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glycyrrhetic acid 3-O-mono-β-D-glucuronide (GAMG) Saccharomyces cerevisiae cytochrome P450 enzymes (CYPs) CRISPR/Cas9 metabolic engineering Biotechnology TP248.13-248.65 |
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glycyrrhetic acid 3-O-mono-β-D-glucuronide (GAMG) Saccharomyces cerevisiae cytochrome P450 enzymes (CYPs) CRISPR/Cas9 metabolic engineering Biotechnology TP248.13-248.65 Ying Huang Dan Jiang Guangxi Ren Yan Yin Yifan Sun Tengfei Liu Chunsheng Liu De Novo Production of Glycyrrhetic Acid 3-O-mono-β-D-glucuronide in Saccharomyces cerevisiae |
description |
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. |
format |
article |
author |
Ying Huang Dan Jiang Guangxi Ren Yan Yin Yifan Sun Tengfei Liu Chunsheng Liu |
author_facet |
Ying Huang Dan Jiang Guangxi Ren Yan Yin Yifan Sun Tengfei Liu Chunsheng Liu |
author_sort |
Ying Huang |
title |
De Novo Production of Glycyrrhetic Acid 3-O-mono-β-D-glucuronide in Saccharomyces cerevisiae |
title_short |
De Novo Production of Glycyrrhetic Acid 3-O-mono-β-D-glucuronide in Saccharomyces cerevisiae |
title_full |
De Novo Production of Glycyrrhetic Acid 3-O-mono-β-D-glucuronide in Saccharomyces cerevisiae |
title_fullStr |
De Novo Production of Glycyrrhetic Acid 3-O-mono-β-D-glucuronide in Saccharomyces cerevisiae |
title_full_unstemmed |
De Novo Production of Glycyrrhetic Acid 3-O-mono-β-D-glucuronide in Saccharomyces cerevisiae |
title_sort |
de novo production of glycyrrhetic acid 3-o-mono-β-d-glucuronide in saccharomyces cerevisiae |
publisher |
Frontiers Media S.A. |
publishDate |
2021 |
url |
https://doaj.org/article/b968d1021b874823a62e52acb421dac0 |
work_keys_str_mv |
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1718406586087505920 |