title: Efficient enzymatic systems for synthesis of novel α-mangostin glycosides exhibiting antibacterial activity against Gram-positive bacteria.
abstract: 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), (1)H and (13)C 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.
authors.affiliation: Institute of Biomolecule Reconstruction (iBR), Department of Pharmaceutical Engineering, Sun Moon University, #100, Kalsan-ri, Tangjeong-myeon, Asan-si, Chungnam, 336-708, Republic of Korea.
authors.forename: Tuoi Thi
authors.initials: TT
authors.lastname: Le
authors.forename: Ramesh Prasad
authors.initials: RP
authors.lastname: Pandey
authors.forename: Rit Bahadur
authors.initials: RB
authors.lastname: Gurung
authors.forename: Dipesh
authors.initials: D
authors.lastname: Dhakal
authors.forename: Jae Kyung
authors.initials: JK
authors.lastname: Sohng
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D001709:Biotechnology / Q000379:methods*; D006027:Glycosides / Q000378:metabolism / Q000494:pharmacology*; D016695:Glycosyltransferases / Q000378:metabolism; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D021241:Spectrometry, Mass, Electrospray Ionization; D013678:Technology, Pharmaceutical / Q000379:methods*; D014532:Uridine Diphosphate Glucose / Q000031:analogs & derivatives / Q000378:metabolism; D044004:Xanthones / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D006027:Glycosides; D044004:Xanthones; C012091:uridine diphosphate 2-deoxyglucose; D016695:Glycosyltransferases; C021053:mangostin; D014532:Uridine Diphosphate Glucose