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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Autores principales: Ying Huang, Dan Jiang, Guangxi Ren, Yan Yin, Yifan Sun, Tengfei Liu, Chunsheng Liu
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Lenguaje:EN
Publicado: Frontiers Media S.A. 2021
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Acceso en línea:https://doaj.org/article/b968d1021b874823a62e52acb421dac0
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spelling 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)
institution DOAJ
collection DOAJ
language EN
topic glycyrrhetic acid 3-O-mono-β-D-glucuronide (GAMG)
Saccharomyces cerevisiae
cytochrome P450 enzymes (CYPs)
CRISPR/Cas9
metabolic engineering
Biotechnology
TP248.13-248.65
spellingShingle 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 AT yinghuang denovoproductionofglycyrrheticacid3omonobdglucuronideinsaccharomycescerevisiae
AT danjiang denovoproductionofglycyrrheticacid3omonobdglucuronideinsaccharomycescerevisiae
AT guangxiren denovoproductionofglycyrrheticacid3omonobdglucuronideinsaccharomycescerevisiae
AT yanyin denovoproductionofglycyrrheticacid3omonobdglucuronideinsaccharomycescerevisiae
AT yifansun denovoproductionofglycyrrheticacid3omonobdglucuronideinsaccharomycescerevisiae
AT tengfeiliu denovoproductionofglycyrrheticacid3omonobdglucuronideinsaccharomycescerevisiae
AT chunshengliu denovoproductionofglycyrrheticacid3omonobdglucuronideinsaccharomycescerevisiae
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