Efficient enzymatic systems for synthesis of novel α-mangostin glycosides exhibiting antibacterial activity against Gram-positive bacteria

• Published in: Applied microbiology and biotechnology Vol. 98; no. 20; pp. 8527 - 8538
• Main Authors: Le, Tuoi Thi, Pandey, Ramesh Prasad, Gurung, Rit Bahadur, Dhakal, Dipesh, Sohng, Jae Kyung
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01-10-2014; Springer Berlin Heidelberg; Springer
• Subjects: 2-deoxyglucose; Analysis; Anti-Bacterial Agents - metabolism; Anti-Bacterial Agents - pharmacology; antibacterial properties; anticarcinogenic activity; Bacillus licheniformis; Bacillus subtilis; Biomedical and Life Sciences; Biotechnological Products and Process Engineering; Biotechnology; Biotechnology - methods; Chemical properties; Enzymes; glucose; Glycosides; Glycosides - metabolism; Glycosides - pharmacology; glycosylation; Glycosyltransferases - metabolism; Gram-positive bacteria; Gram-Positive Bacteria - drug effects; incubation period; Life Sciences; Microbial Genetics and Genomics; Microbiology; Micrococcus luteus; nuclear magnetic resonance spectroscopy; Product development; recycling; Spectrometry, Mass, Electrospray Ionization; Staphylococcus aureus; Technology, Pharmaceutical - methods; Uridine Diphosphate Glucose - analogs & derivatives; Uridine Diphosphate Glucose - metabolism; water solubility; Xanthones - metabolism; Xanthones - pharmacology; Antibacterial activity; Mangostin; Mangostin glycosides; One-pot reaction
• ISSN: 0175-7598; 1432-0614
• DOI: 10.1007/s00253-014-5947-5

Two enzymatic systems were developed for the efficient synthesis of glycoside products of α-mangostin, a natural xanthonoid exhibiting anti-oxidant, antibacterial, anti-inflammatory, and anticancer activities. In these systems, one-pot reactions for the synthesis of UDP-α-D-glucose and UDP-α-D-2-deoxyglucose were modified and combined with a glycosyltransferase (GT) from Bacillus licheniformis DSM-13 to afford C-3 and C-6 position modified glucose and 2-deoxyglucose conjugated novel α-mangostin derivatives. α-Mangostin 3-O-β-D-glucopyranoside, α-mangostin 6-O-β-D-glucopyranoside, α-mangostin 3,6-di-O-β-D-glucopyranoside, α-mangostin 3-O-β-D-2-deoxyglucopyranoside, α-mangostin 6-O-β-D-2-deoxyglucopyranoside, and α-mangostin 3,6-di-O-β-D-2-deoxyglucopyranoside were successfully produced in practical quantities and characterized by high-resolution quadruple time-of-flight electrospray ionization-mass spectrometry (HR-QTOF ESI/MS), ¹H and ¹³C NMR analyses. In excess of the substrate, the maximum productions of three α-mangostin glucopyranosides (4.8 mg/mL, 86.5 % overall conversion of α-mangostin) and three α-mangostin 2-deoxyglucopyronosides (4.0 mg/mL, 79 % overall conversion of α-mangostin) were achieved at 4-h incubation period. All the α-mangostin glycosides exhibited improved water solubility, and their antibacterial activity against three Gram-positive bacteria Micrococcus luteus, Bacillus subtilis, and Staphylococcus aureus was drastically enhanced by the glucosylation at C-3 position. In this study, diverse glycosylated α-mangostin were produced in significant quantities by using inexpensive starting materials and recycling co-factors within a reaction vessel without use of expensive NDP-sugars in the glycosylation reactions.