Enzymatic Synthesis of Novel Glycyrrhizic Acid Glucosides Using a Promiscuous <i>Bacillus</i> Glycosyltransferase
Glycyrrhetinic acid (GA) and glycyrrhizin (GA-3-<i>O</i>-[<i>β</i>-<span style="font-variant: small-caps;">d</span>-glucuronopyranosyl-(1→2)-<i>β</i>-<span style="font-variant: small-caps;">d</sp...
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MDPI AG
2018-12-01
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| Series: | Catalysts |
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| author | Longhai Dai Jiao Li Jiangang Yang Yan Men Yan Zeng Yi Cai Yuanxia Sun |
| author_facet | Longhai Dai Jiao Li Jiangang Yang Yan Men Yan Zeng Yi Cai Yuanxia Sun |
| author_sort | Longhai Dai |
| collection | DOAJ |
| description | Glycyrrhetinic acid (GA) and glycyrrhizin (GA-3-<i>O</i>-[<i>β</i>-<span style="font-variant: small-caps;">d</span>-glucuronopyranosyl-(1→2)-<i>β</i>-<span style="font-variant: small-caps;">d</span>-glucuronopyranoside], GL) are the major bioactive components of <i>Glycyrrhiza uralensis</i> and possess multifarious notable biological activities. UDP-glycosyltransferase (UGT)⁻catalyzed glycosylation remarkably extends the structural and functional diversification of GA-glycoside derivatives. In this study, six glucosides (<b>1</b>⁻<b>6</b>) of GA and GL were synthesized using a <i>Bacillus subtilis</i> 168⁻originated flexible UDP-glycosyltransferase Bs-YjiC. Bs-YjiC could transfer a glucosyl moiety from UDP-glucose to the free C3 hydroxyl and/or C30 carboxyl groups of GA and GL and further elongate the C30 glucosyl chain via a <i>β</i>-1-2-glycosidic bond. Glycosylation significantly increased the water solubility of these novel glucosides by 4⁻90 folds. In vitro assays showed that GA monoglucosides (<b>1</b> and <b>2</b>) showed stronger antiproliferative activity against human liver cancer cells HepG2 and breast cancer cells MCF-7 than that of GL and GL glucosides. These findings provide significant insights into the important role of promiscuous UGTs for the enzymatic synthesis of novel bioactive GA derivatives. |
| first_indexed | 2024-04-13T07:26:21Z |
| format | Article |
| id | doaj.art-ec197c1389ff4a2c861909883b5290b6 |
| institution | Directory Open Access Journal |
| issn | 2073-4344 |
| language | English |
| last_indexed | 2024-04-13T07:26:21Z |
| publishDate | 2018-12-01 |
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| series | Catalysts |
| spelling | doaj.art-ec197c1389ff4a2c861909883b5290b62022-12-22T02:56:28ZengMDPI AGCatalysts2073-43442018-12-0181261510.3390/catal8120615catal8120615Enzymatic Synthesis of Novel Glycyrrhizic Acid Glucosides Using a Promiscuous <i>Bacillus</i> GlycosyltransferaseLonghai Dai0Jiao Li1Jiangang Yang2Yan Men3Yan Zeng4Yi Cai5Yuanxia Sun6National Engineering Laboratory for Industrial Enzymes, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, ChinaNational Engineering Laboratory for Industrial Enzymes, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, ChinaNational Engineering Laboratory for Industrial Enzymes, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, ChinaNational Engineering Laboratory for Industrial Enzymes, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, ChinaNational Engineering Laboratory for Industrial Enzymes, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, ChinaNational Engineering Laboratory for Industrial Enzymes, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, ChinaNational Engineering Laboratory for Industrial Enzymes, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, ChinaGlycyrrhetinic acid (GA) and glycyrrhizin (GA-3-<i>O</i>-[<i>β</i>-<span style="font-variant: small-caps;">d</span>-glucuronopyranosyl-(1→2)-<i>β</i>-<span style="font-variant: small-caps;">d</span>-glucuronopyranoside], GL) are the major bioactive components of <i>Glycyrrhiza uralensis</i> and possess multifarious notable biological activities. UDP-glycosyltransferase (UGT)⁻catalyzed glycosylation remarkably extends the structural and functional diversification of GA-glycoside derivatives. In this study, six glucosides (<b>1</b>⁻<b>6</b>) of GA and GL were synthesized using a <i>Bacillus subtilis</i> 168⁻originated flexible UDP-glycosyltransferase Bs-YjiC. Bs-YjiC could transfer a glucosyl moiety from UDP-glucose to the free C3 hydroxyl and/or C30 carboxyl groups of GA and GL and further elongate the C30 glucosyl chain via a <i>β</i>-1-2-glycosidic bond. Glycosylation significantly increased the water solubility of these novel glucosides by 4⁻90 folds. In vitro assays showed that GA monoglucosides (<b>1</b> and <b>2</b>) showed stronger antiproliferative activity against human liver cancer cells HepG2 and breast cancer cells MCF-7 than that of GL and GL glucosides. These findings provide significant insights into the important role of promiscuous UGTs for the enzymatic synthesis of novel bioactive GA derivatives.https://www.mdpi.com/2073-4344/8/12/615glycyrrhetinic acidglycyrrhizin<i>Bacillus</i> UDP-glycosyltransferaseglycosylationcytotoxicity |
| spellingShingle | Longhai Dai Jiao Li Jiangang Yang Yan Men Yan Zeng Yi Cai Yuanxia Sun Enzymatic Synthesis of Novel Glycyrrhizic Acid Glucosides Using a Promiscuous <i>Bacillus</i> Glycosyltransferase Catalysts glycyrrhetinic acid glycyrrhizin <i>Bacillus</i> UDP-glycosyltransferase glycosylation cytotoxicity |
| title | Enzymatic Synthesis of Novel Glycyrrhizic Acid Glucosides Using a Promiscuous <i>Bacillus</i> Glycosyltransferase |
| title_full | Enzymatic Synthesis of Novel Glycyrrhizic Acid Glucosides Using a Promiscuous <i>Bacillus</i> Glycosyltransferase |
| title_fullStr | Enzymatic Synthesis of Novel Glycyrrhizic Acid Glucosides Using a Promiscuous <i>Bacillus</i> Glycosyltransferase |
| title_full_unstemmed | Enzymatic Synthesis of Novel Glycyrrhizic Acid Glucosides Using a Promiscuous <i>Bacillus</i> Glycosyltransferase |
| title_short | Enzymatic Synthesis of Novel Glycyrrhizic Acid Glucosides Using a Promiscuous <i>Bacillus</i> Glycosyltransferase |
| title_sort | enzymatic synthesis of novel glycyrrhizic acid glucosides using a promiscuous i bacillus i glycosyltransferase |
| topic | glycyrrhetinic acid glycyrrhizin <i>Bacillus</i> UDP-glycosyltransferase glycosylation cytotoxicity |
| url | https://www.mdpi.com/2073-4344/8/12/615 |
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