Research abstract
Article abstract
Nature Biotechnology 25, 454 - 464 (2007)
Published online: 1 April 2007 | doi:10.1038/nbt1298
Bacterial glycosidases for the production of universal red blood cells
Qiyong P Liu1,9, Gerlind Sulzenbacher2,9, Huaiping Yuan1, Eric P Bennett3, Greg Pietz1,3, Kristen Saunders1, Jean Spence1, Edward Nudelman1, Steven B Levery4, Thayer White1, John M Neveu5, William S Lane5, Yves Bourne2, Martin L Olsson6,7, Bernard Henrissat2 & Henrik Clausen3,8
Abstract
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 
-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.
- ZymeQuest Inc., 100 Cummings Center, Suite 436H, Beverly, Massachusetts 01915, USA.
- Architecture et Fonction des Macromolécules Biologiques, UMR6098, CNRS, Universités Aix-Marseille I & II, Case 932, 163 Avenue de Luminy, 13288 Marseille Cedex 9, France.
- Departments of Cellular and Molecular Medicine and Oral Diagnostics, University of Copenhagen, Blegdamsvej, DK-2200 Copenhagen N, Denmark.
- Department of Chemistry, University of New Hampshire, Durham, New Hampshire 03824, USA.
- Harvard Microchemistry and Proteomics Analysis Facility, Harvard University, Cambridge, Massachusetts 02138, USA.
- Division of Hematology and Transfusion Medicine, Department of Laboratory Medicine, Lund University and University Hospital Blood Center, SE-22185, Lund, Sweden.
- Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.
- Hematology Division Brigham & Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
- These authors contributed equally to this work.
Correspondence to: Gerlind Sulzenbacher2,9 e-mail: gerlind.sulzenbacher@afmb.univ-mrs.fr
Correspondence to: Henrik Clausen3,8 e-mail: hc@imbg.ku.dk
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