title: Enzymatic glycosylation of the topical antibiotic mupirocin.
abstract: Mupirocin is a commercially available antibiotic that acts on bacterial isoleucyl-tRNA synthetase, thereby inhibiting protein synthesis and preventing bacterial infection. An in vitro glycosylation approach was applied to synthesize glycoside derivatives of mupirocin using different NDP-sugars and glycosyltransferase from Bacillus licheniformis. Ultra pressure liquid chromatography-photo diode array analyses of the reaction mixtures revealed the generation of product peak(s). The results were further supported by high-resolution quadruple time of flight electrospray ionization mass spectrometry analyses. The product purified from the reaction mixture with UDP-D-glucose was subjected to NMR analysis, and the structure was determined to be mupirocin 6-O-β-D-glucoside. Other glycoside analogs of mupirocin were determined based on high-resolution mass analyses. Antibacterial activity assays against Staphylococcus aureus demonstrated complete loss of antibacterial activity after glucosylation of mupirocin at the 6-hydroxyl position.
authors: Institute of Biomolecule Reconstruction, Department of Pharmaceutical Engineering, Sun Moon University, 100 Kalsan-ri, Tangjeonmyun, Asan-si, Chungnam, 336-708, Korea.
authors: Prakash
authors: P
authors: Parajuli
authors: Ramesh Prasad
authors: RP
authors: Pandey
authors: Anaya Raj
authors: AR
authors: Pokhrel
authors: Gopal Prasad
authors: GP
authors: Ghimire
authors: Jae Kyung
authors: JK
authors: Sohng
mesh_terms: D000287:Administration, Topical; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D055162:Biocatalysis / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D005960:Glucosides / Q000378:metabolism; D006001:Glycoconjugates / Q000378:metabolism; D006031:Glycosylation / Q000187:drug effects; D016695:Glycosyltransferases / Q000302:isolation & purification / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008826:Microbial Sensitivity Tests; D016712:Mupirocin / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D066244:Proton Magnetic Resonance Spectroscopy; D021241:Spectrometry, Mass, Electrospray Ionization; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D005960:Glucosides; D006001:Glycoconjugates; D016712:Mupirocin; D016695:Glycosyltransferases