Bacterial glycosidases for the production of universal red blood cells.
Enzymatic removal of blood group ABO antigens to develop universal red blood cells (RBCs) was a pioneering vision originally proposed more than 25 years ago. Although the feasibility of this approach was demonstrated in clinical trials for group B RBCs, a major obstacle in translating this technology to clinical practice has been the lack of efficient glycosidase enzymes. Here we report two bacterial glycosidase gene families that provide enzymes capable of efficient removal of A and B antigens at neutral pH with low consumption of recombinant enzymes. The crystal structure of a member of the alpha-N-acetylgalactosaminidase family reveals an unusual catalytic mechanism involving NAD+. The enzymatic conversion processes we describe hold promise for achieving the goal of producing universal RBCs, which would improve the blood supply while enhancing the safety of clinical transfusions.
Liu
Qiyong P
QP
ZymeQuest Inc., 100 Cummings Center, Suite 436H, Beverly, Massachusetts 01915, USA.
Sulzenbacher
Gerlind
G
Yuan
Huaiping
H
Bennett
Eric P
EP
Pietz
Greg
G
Saunders
Kristen
K
Spence
Jean
J
Nudelman
Edward
E
Levery
Steven B
SB
White
Thayer
T
Neveu
John M
JM
Lane
William S
WS
Bourne
Yves
Y
Olsson
Martin L
ML
Henrissat
Bernard
B
Clausen
Henrik
H
D000017:ABO Blood-Group System / Q000737:chemistry; D001419:Bacteria / Q000201:enzymology*; D001665:Binding Sites; D001788:Blood Grouping and Crossmatching; D002384:Catalysis; D002855:Chromatography, Thin Layer; D004912:Erythrocytes / Q000378:metabolism*; D005434:Flow Cytometry; D006026:Glycoside Hydrolases / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008969:Molecular Sequence Data; D011387:Prokaryotic Cells / Q000201:enzymology; D017433:Protein Structure, Secondary; D013379:Substrate Specificity; D017186:Titrimetry; D048809:alpha-N-Acetylgalactosaminidase / Q000737:chemistry
D000017:ABO Blood-Group System; D006026:Glycoside Hydrolases; D048809:alpha-N-Acetylgalactosaminidase