34 research outputs found
Antibacterial Strategy against H. pylori: Inhibition of the Radical SAM Enzyme MqnE in Menaquinone Biosynthesis
Evolutionarily Distinct Versions of the Multidomain Enzyme α-Isopropylmalate Synthase Share Discrete Mechanisms of V-Type Allosteric Regulation
Direct Spectroscopic Evidence for a High-Spin Fe(IV) Intermediate in Tyrosine Hydroxylase
Chemoenzymatic synthesis of GDP-l-fucose and the Lewis X glycan derivatives
Lewis X (Lex)-containing glycans play important roles in numerous cellular processes. However, the absence of robust, facile, and cost-effective methods for the synthesis of Lex and its structurally related analogs has severely hampered the elucidation of the specific functions of these glycan epitopes. Here we demonstrate that chemically defined guanidine 5′-diphosphate-β-l-fucose (GDP-fucose), the universal fucosyl donor, the Lex trisaccharide, and their C-5 substituted derivatives can be synthesized on preparative scales, using a chemoenzymatic approach. This method exploits l-fucokinase/GDP-fucose pyrophosphorylase (FKP), a bifunctional enzyme isolated from Bacteroides fragilis 9343, which converts l-fucose into GDP-fucose via a fucose-1-phosphate (Fuc-1-P) intermediate. Combining the activities of FKP and a Helicobacter pylori α1,3 fucosyltransferase, we prepared a library of Lex trisaccharide glycans bearing a wide variety of functional groups at the fucose C-5 position. These neoglycoconjugates will be invaluable tools for studying Lex-mediated biological processes