Identification of the D-glucuronyl C5-epimerase that introduces iduronic acid into N-linked glycans decorating archaeal glycoproteins

In Halobacterium salinarum, halophilic archaea that grow in saturated salt solutions, glycoproteins are modified by an N-linked tetrasaccharide that includes iduronic acid (IdoA). This represents the only known example of IdoA, a sugar better known as a component of glycosaminoglycans found in various eukaryal tissues, in N-glycosylation. Although much of the pathway used to assemble this tetrasaccharide is defined, the epimerase that presumably converts glucuronic acid (GlcA) into IdoA had yet to be described. In silico predictions assign this role to VNG1058H. In Hbt. salinarum deleted of VNG1058H, an N-linked tetrasaccharide appeared in which IdoA is replaced by GlcA and greatly reduced sulfation of the last two tetrasaccharide sugars is noted. The absence of VNG1058H, moreover, affects cell physiology. Furthermore, Hbt. salinarum differentially transcribe VNG1058H as a function of growth temperature, suggestive of a response to environmental change. VNG1058H is the first D-glucuronyl C5-epimerase to be identified in Archaea.