Ketodeoxynonulosonic Acid Hydroxylase (Kdnase) Assisted Site-Specific Enzymatic α2,6-Sialylation
Yu Zhou
Key Laboratory of Marine Drugs of Ministry of Education, Shandong Key Laboratory of Glycoscience and Glycotherapeutics, School of Medicine and Pharmacy, Ocean University of China, Qingdao, Shandong, 266003 China
State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, 300353 China
These authors contribute equally.
Search for more papers by this authorYun Li
Key Laboratory of Marine Drugs of Ministry of Education, Shandong Key Laboratory of Glycoscience and Glycotherapeutics, School of Medicine and Pharmacy, Ocean University of China, Qingdao, Shandong, 266003 China
These authors contribute equally.
Search for more papers by this authorJiayu Wen
State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, 300353 China
Department of Pharmacy and Health Management, Hebei Chemical and Pharmaceutical College, Shijiazhuang, Hebei, 050026 China
These authors contribute equally.
Search for more papers by this authorYan Zhang
Key Laboratory of Marine Drugs of Ministry of Education, Shandong Key Laboratory of Glycoscience and Glycotherapeutics, School of Medicine and Pharmacy, Ocean University of China, Qingdao, Shandong, 266003 China
Search for more papers by this authorCorresponding Author
Zhifei Hu
Key Laboratory of Marine Drugs of Ministry of Education, Shandong Key Laboratory of Glycoscience and Glycotherapeutics, School of Medicine and Pharmacy, Ocean University of China, Qingdao, Shandong, 266003 China
E-mail: [email protected]; [email protected]; [email protected]; [email protected]Search for more papers by this authorCorresponding Author
Kan Zhong
Key Laboratory of Marine Drugs of Ministry of Education, Shandong Key Laboratory of Glycoscience and Glycotherapeutics, School of Medicine and Pharmacy, Ocean University of China, Qingdao, Shandong, 266003 China
E-mail: [email protected]; [email protected]; [email protected]; [email protected]Search for more papers by this authorCorresponding Author
Hongzhi Cao
Key Laboratory of Marine Drugs of Ministry of Education, Shandong Key Laboratory of Glycoscience and Glycotherapeutics, School of Medicine and Pharmacy, Ocean University of China, Qingdao, Shandong, 266003 China
Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao, Shandong, 266237 China
E-mail: [email protected]; [email protected]; [email protected]; [email protected]Search for more papers by this authorCorresponding Author
Jiansong Cheng
State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, 300353 China
E-mail: [email protected]; [email protected]; [email protected]; [email protected]Search for more papers by this authorYu Zhou
Key Laboratory of Marine Drugs of Ministry of Education, Shandong Key Laboratory of Glycoscience and Glycotherapeutics, School of Medicine and Pharmacy, Ocean University of China, Qingdao, Shandong, 266003 China
State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, 300353 China
These authors contribute equally.
Search for more papers by this authorYun Li
Key Laboratory of Marine Drugs of Ministry of Education, Shandong Key Laboratory of Glycoscience and Glycotherapeutics, School of Medicine and Pharmacy, Ocean University of China, Qingdao, Shandong, 266003 China
These authors contribute equally.
Search for more papers by this authorJiayu Wen
State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, 300353 China
Department of Pharmacy and Health Management, Hebei Chemical and Pharmaceutical College, Shijiazhuang, Hebei, 050026 China
These authors contribute equally.
Search for more papers by this authorYan Zhang
Key Laboratory of Marine Drugs of Ministry of Education, Shandong Key Laboratory of Glycoscience and Glycotherapeutics, School of Medicine and Pharmacy, Ocean University of China, Qingdao, Shandong, 266003 China
Search for more papers by this authorCorresponding Author
Zhifei Hu
Key Laboratory of Marine Drugs of Ministry of Education, Shandong Key Laboratory of Glycoscience and Glycotherapeutics, School of Medicine and Pharmacy, Ocean University of China, Qingdao, Shandong, 266003 China
E-mail: [email protected]; [email protected]; [email protected]; [email protected]Search for more papers by this authorCorresponding Author
Kan Zhong
Key Laboratory of Marine Drugs of Ministry of Education, Shandong Key Laboratory of Glycoscience and Glycotherapeutics, School of Medicine and Pharmacy, Ocean University of China, Qingdao, Shandong, 266003 China
E-mail: [email protected]; [email protected]; [email protected]; [email protected]Search for more papers by this authorCorresponding Author
Hongzhi Cao
Key Laboratory of Marine Drugs of Ministry of Education, Shandong Key Laboratory of Glycoscience and Glycotherapeutics, School of Medicine and Pharmacy, Ocean University of China, Qingdao, Shandong, 266003 China
Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao, Shandong, 266237 China
E-mail: [email protected]; [email protected]; [email protected]; [email protected]Search for more papers by this authorCorresponding Author
Jiansong Cheng
State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, 300353 China
E-mail: [email protected]; [email protected]; [email protected]; [email protected]Search for more papers by this authorComprehensive 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 the synthesis of various α2,6-linked sialosides. However, Pd2,6ST is not a suitable enzyme for the regioselective α2,6-sialylation of complex acceptor substrates containing multiple galactose (Gal) and/or N-acetylgalactosamine (GalNAc) residues due to its promiscuous substrate specificity. In this study, a novel enzymatic substrate engineering strategy was developed to overcome this limitation by employing enzymatically introduced α2,6-linked ketodeoxynonulosonic acid (Kdn) as temporary “protecting group” at the unwanted sialylation sites. The Kdn “protecting group” can be selectively removed by a ketodeoxynonulosonic acid hydrolase from Aspergillus fumigatus (AfKdnase) at appropriate stage without affecting coexisting sialic acid residues, such as N-acetylneuraminic acid (Neu5Ac) or N-glycolylneuraminic acid (Neu5Gc). This strategy provides a general and practical approach for the synthesis of complex sialosides, including sialylated poly-LacNAc glycans, disialylated ganglioside glycan epitopes, and branched human milk oligosaccharides.
Supporting Information
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Appendix S1: Supporting Information |
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