Bacterial Glycosidases for the Production of Universal Red Blood Cells

Nat Biotechnol. 2007 Apr;25(4):454-64. doi: 10.1038/nbt1298. Epub 2007 Apr 1.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ABO Blood-Group System / chemistry
  • Bacteria / enzymology*
  • Binding Sites
  • Blood Grouping and Crossmatching
  • Catalysis
  • Chromatography, Thin Layer
  • Erythrocytes / metabolism*
  • Flow Cytometry
  • Glycoside Hydrolases / metabolism*
  • Humans
  • Hydrogen-Ion Concentration
  • Kinetics
  • Molecular Sequence Data
  • Prokaryotic Cells / enzymology
  • Protein Structure, Secondary
  • Substrate Specificity
  • Titrimetry
  • alpha-N-Acetylgalactosaminidase / chemistry

Substances

  • ABO Blood-Group System
  • Glycoside Hydrolases
  • alpha-N-Acetylgalactosaminidase

Associated data

  • GENBANK/AM039444
  • GENBANK/AM039445
  • GENBANK/AM039446
  • GENBANK/AM039447
  • GENBANK/AM039448
  • GENBANK/AM039449
  • GENBANK/AM109953
  • GENBANK/AM109954
  • GENBANK/AM109955
  • GENBANK/AM109956
  • GENBANK/AM109957
  • PDB/2IXA
  • PDB/2IXB