Ketodeoxynonulosonic Acid Hydroxylase (Kdnase) Assisted Site‐Specific Enzymatic α2,6‐Sialylation DOI Open Access

Yu Zhou,

Yun Li, Jiayu Wen

et al.

Chinese Journal of Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: March 26, 2025

Comprehensive Summary Owing to its promiscuous substrate specificity and high catalytic efficiency, the bacterial α2,6‐sialyltransferase from Photobacterium damselae (Pd2,6ST) has been widely used for synthesis of various α2,6‐linked sialosides. However, Pd2,6ST is not a suitable enzyme regioselective α2,6‐sialylation complex acceptor substrates containing multiple galactose (Gal) and/or N ‐acetylgalactosamine (GalNAc) residues due specificity. In this study, novel enzymatic engineering strategy was developed overcome limitation by employing enzymatically introduced ketodeoxynonulosonic acid (Kdn) as temporary “protecting group” at unwanted sialylation sites. The Kdn can be selectively removed hydrolase Aspergillus fumigatus ( Af Kdnase) appropriate stage without affecting coexisting sialic residues, such ‐acetylneuraminic (Neu5Ac) or ‐glycolylneuraminic (Neu5Gc). This provides general practical approach sialosides, including sialylated poly‐LacNAc glycans, disialylated ganglioside glycan epitopes, branched human milk oligosaccharides.

Language: Английский

Ketodeoxynonulosonic Acid Hydroxylase (Kdnase) Assisted Site‐Specific Enzymatic α2,6‐Sialylation DOI Open Access

Yu Zhou,

Yun Li, Jiayu Wen

et al.

Chinese Journal of Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: March 26, 2025

Comprehensive Summary Owing to its promiscuous substrate specificity and high catalytic efficiency, the bacterial α2,6‐sialyltransferase from Photobacterium damselae (Pd2,6ST) has been widely used for synthesis of various α2,6‐linked sialosides. However, Pd2,6ST is not a suitable enzyme regioselective α2,6‐sialylation complex acceptor substrates containing multiple galactose (Gal) and/or N ‐acetylgalactosamine (GalNAc) residues due specificity. In this study, novel enzymatic engineering strategy was developed overcome limitation by employing enzymatically introduced ketodeoxynonulosonic acid (Kdn) as temporary “protecting group” at unwanted sialylation sites. The Kdn can be selectively removed hydrolase Aspergillus fumigatus ( Af Kdnase) appropriate stage without affecting coexisting sialic residues, such ‐acetylneuraminic (Neu5Ac) or ‐glycolylneuraminic (Neu5Gc). This provides general practical approach sialosides, including sialylated poly‐LacNAc glycans, disialylated ganglioside glycan epitopes, branched human milk oligosaccharides.

Language: Английский

Citations

0