Enzymatic Synthesis of Novel Glycyrrhizic Acid Glucosides Using a Promiscuous <i>Bacillus</i> Glycosyltransferase
oleh: Longhai Dai, Jiao Li, Jiangang Yang, Yan Men, Yan Zeng, Yi Cai, Yuanxia Sun
| Format: | Article |
|---|---|
| Diterbitkan: | MDPI AG 2018-12-01 |
Deskripsi
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.