Turning universal O into rare Bombay type blood

Area of Science:

• Biochemistry
• Hematology
• Microbiology

Background:

• Red blood cell antigens are crucial for safe blood transfusions.
• The Bombay phenotype (lack of H antigen) requires specific O_h blood transfusions, posing challenges due to rarity.
• Incompatibility in blood transfusions can lead to life-threatening reactions.

Purpose of the Study:

• To identify and characterize an enzyme capable of generating the afucosylated Bombay phenotype.
• To explore the potential of this enzyme in facilitating blood transfusions for Bombay phenotype individuals.

Main Methods:

• Discovery and characterization of FucOB, an α-1,2-fucosidase from *Akkermansia muciniphila*.
• X-ray crystallography to determine the enzyme's three-domain structure, including the GH95 hydrolase domain.
• Site-directed mutagenesis, enzymatic assays, and computational methods to understand substrate specificity and catalysis.
• Agglutination tests and flow cytometry to validate the enzyme's efficacy in converting blood types.

Main Results:

• FucOB effectively hydrolyzes Type I, II, III, and V H antigens, producing an afucosylated phenotype in vitro.
• Structural analysis revealed key insights into FucOB's catalytic mechanism and substrate interactions.
• The enzyme successfully converted universal O type blood into the rare Bombay type in laboratory tests.

Conclusions:

• FucOB is a novel α-1,2-fucosidase with the ability to generate the Bombay blood phenotype.
• This enzymatic approach presents a promising strategy for producing compatible blood for transfusion in Bombay phenotype patients.
• The findings open new avenues for managing transfusion challenges in rare blood group incompatibilities.