ADV SYNTH CATAL, 368, 8, e70413 1-19 (2026)

IF 4,0

Characterization of the Human Blood Group Glycosyltransferases GTA and GTB for the Synthesis of Blood Group Antigens

Pöstges Katja, Palm Philip, Hussnaetter Kai P., Filipová Eliška, Pelantová Helena, Petrásková Lucie, Bojarová Pavla, Křen Vladimír, Elling Lothar

 Abstract

Blood group antigens are critical determinants in transfusion medicine and immune responses, yet their enzymatic synthesis from complex glycans remains challenging. In this study, we recombinantly produced and characterized the human glycosyltransferases GTA and GTB in Escherichia coli for the synthesis of A and B blood group antigens. GTA and GTB showed strong Mn²⁺-dependence, high catalytic efficiency toward their donor substrates UDP-GalNAc and UDP-Gal, respectively, and a broad tolerance for human milk oligosaccharide (HMO)-and poly-N-acetyllactosamine (poly-LacNAc)-derived acceptor substrates. The combination of GTA and GTB with the bacterial α2-fucosyltransferase FutC was investigated using one-pot and stepwise synthetic strategies. We achieved efficient synthesis of the complex A and B blood group hexasaccharides, thereby demonstrating for the first time the enzymatic synthesis of blood group antigens from tetraose HMOs and tetraose poly-LacNAc acceptors. These include A-LNT (35 mg/56%), B-LNT (11 mg/17%), A-LNnT (22 mg/35%), B-LNnT (13 mg/22%), A-LN1-LN2 (55 mg/89%), B-LN1-LN2 (54 mg/100%), A-LN2-LN2 (23 mg/50%), and B-LN2-LN2 (9 mg/42%). In total, 14 ABH(O) blood group glycans were synthesized. Our study establishes enzymatic cascades as a versatile and sustainable approach to blood group antigen synthesis, paving the way for future applications in glycoengineering and studies of antibody and lectin glycoconjugate interactions in biomedicine.

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