An enzymatic pathway in the human gut microbiome that converts A to universal O type blood

2020-06-15

For emergency transfusions,blood group O negative is the variety of blood that has the lowest risk of causing serious reactions for most people who receive it. Because of this, it's sometimes called the universal blood donor type.To up the supply of universal blood, scientists have tried transforming the second most common blood, type A by removing the antigens. But they’ve met with limited success, as the known enzymes that can strip the red blood cell of the offending sugars aren’t efficient enough to do the job economically.

When scientist tested two of the resulting enzymes at once—adding them to substances that would glow if the sugars were removed. The enzymes also worked their magic in human blood. The enzymes originally come from a gut bacterium called Flavonifractor plautii, Rahfeld, Withers, and their colleagues report today in Nature Microbiology. Tiny amounts added to a unit of type A blood could get rid of the offending sugars, they found. “The findings are very promising in terms of their practical utility,” Narla says. In the United States, type A blood makes up just under one-third of the supply, meaning the availability of “universal” donor blood could almost double.

"Access to efficient enzymes that can convert A and B type red blood cells to ‘universal’ donor O would greatly increase the supply of blood for transfusions.Here we report the functional metagenomic screening of the human gut microbiome for enzymes that can remove the cognate A and B type sugar antigens. Among the genes encoded in our library of 19,500 expressed fosmids bearing gut bacterial DNA, we identify an enzyme pair from the obligate anaerobe Flavonifractor plautii that work in concert to efficiently convert the A antigen to the H antigen of O type blood, via a galactosamine intermediate. The X-ray structure of the N-acetylgalactosamine deacetylase reveals the active site and mechanism of the founding member of an esterase family. The galactosaminidase expands activities within the CAZy family GH36. Their ability to completely convert A to O of the same rhesus type at very low enzyme concentrations in whole blood will simplify their incorporation into blood transfusion practice, broadening blood supply..."

https://doi.org/10.1038/s41564-019-0469-7

-Nature Microbiology


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