Edward Moh (@mredwardmoh.bsky.social)

Polysialic Acid Synthesis on the N- and O-Glycans of Salmonid Polysialyltransferase ST8Sia IV Extension of N- and O-glycans with linear sialic acid polymers (polySias) was described on a limited number of mammalian glycoproteins, including the α2,8-polysialyltransferases ST8Sia II and ST8Sia IV. Previous in vitro analyses have shown that ST8Sia IV from the salmonid fish Coregonus maraena (Cma) had high polysialylation activity and broader donor substrate specificity compared to its human counterpart. In this study, we investigated whether the fish ST8Sia IV was able to polysialylate N- and O-glycans of glycoproteins with a focus on its autopolysialylation capacity. Using a combination of strategies, including plant-based glycoengineering, we found that the Cma ST8Sia IV is able to use both types of acceptors for the formation of long polySia chains with a degree of polymerization of >40 consisting of N-acetylneuraminic acid and N-glycolylneuraminic acid. Given the importance of polySias in multiple health and disease states, the Cma ST8Sia IV represents a useful biocatalyst with applications in the fields of biosafe therapeutics and glycobiology. https://pubs.acs.org/doi/full/10.1021/acsomega.5c12731