Structural Determination and Chemical Synthesis of the <i>N</i>-Glycan from <i>Thermococcus kodakarensis</i>: Discovery of a Highly Glycosylated <i>myo</i>-Inositol Core

Glycosylation is one of the most abundant post-translational modifications and is essential for various biological phenomena. Herein, we describe the isolation, structural determination, and chemical synthesis of the N-glycan from the hyperthermophilic archaeon Thermococcus kodakarensis. The N-glycan from the organism possesses a unique structure including myo-inositol, which has not been found in previously characterized N-glycans. In this structure, myo-inositol is highly glycosylated and linked with a disaccharide unit through a phosphodiester. The straightforward synthesis of this glycan was accomplished through diastereoselective phosphorylation and phosphodiester construction by SN2 coupling. As hyperthermophilic lineages diverged early during evolution, this study can be expected to open the door to approaching the primitive function of glycan modification at the molecular level.