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

Two enzymatic systems were developed for the efficient synthesis of glycoside products of alpha-mangostin, a natural xanthonoid exhibiting anti-oxidant, antibacterial, anti-inflammatory, and anticancer activities. In these systems, one-pot reactions for the synthesis of UDP-alpha-D-glucose and UDP-alpha-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 alpha-mangostin derivatives. alpha-Mangostin 3-O-beta-D-glucopyranoside, alpha-mangostin 6-O-beta-D-glucopyranoside, alpha-mangostin 3,6-di-O-beta-D-glucopyranoside, alpha-mangostin 3-O-beta-D-2-deoxyglucopyranoside, alpha-mangostin 6-O-beta-D-2-deoxyglucopyranoside, and alpha-mangostin 3,6-di-O-beta-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), H-1 and C-13 NMR analyses. In excess of the substrate, the maximum productions of three alpha-mangostin glucopyranosides (4.8 mg/mL, 86.5 % overall conversion of alpha-mangostin) and three alpha-mangostin 2-deoxyglucopyronosides (4.0 mg/mL, 79 % overall conversion of alpha-mangostin) were achieved at 4-h incubation period. All the alpha-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 alpha-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.