A team of researchers headed by University of British Columbia scientist Stephen Withers reports on enzymes — from the human gut — that remove A or B antigens from red blood cells 30 times more efficiently than previously reported enzymes.

“We have been particularly interested in enzymes that allow us to remove the A or B antigens from red blood cells. If you can remove those antigens, which are just simple sugars, then you can convert A or B to O blood,” Dr. Withers said.

“Scientists have pursued the idea of adjusting donated blood to a common type for a while, but they have yet to find efficient, selective enzymes that are also safe and economical.”

To assess potential enzyme candidates more quickly, Dr. Withers and colleagues used a technique called metagenomics.

“With metagenomics, you take all of the organisms from an environment and extract the sum total DNA of those organisms all mixed up together,” Dr. Withers said.

“Casting such a wide net allows us to sample the genes of millions of microorganisms without the need for individual cultures.”

“We then use E. coli to select for DNA containing genes that code for enzymes that can cleave sugar residues.”

The team considered sampling DNA from mosquitoes and leeches, the types of organisms that degrade blood, but ultimately found successful candidate enzymes in the human gut microbiome.

Glycosylated proteins called mucins line the gut wall, providing sugars that serve as attachment points for gut bacteria while also feeding them as they assist in digestion.

Some of the mucin sugars are similar in structure to the antigens on A- and B-type blood.

The scientists homed in on the enzymes the bacteria use to pluck the sugars off mucin and found a new family of enzymes that are 30 times more effective at removing red blood cell antigens than previously reported candidates.

“We are now working to validate these enzymes and test them on a larger scale for potential clinical testing,” they said.

“In addition, we plan to carry out directed evolution, a protein engineering technique that simulates natural evolution, with the goal of creating the most efficient sugar-removing enzyme.”

The researchers presented their results today at the 256th National Meeting & Exposition of the American Chemical Society in Boston, Massachusetts.

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Stephen G. Withers. 2018. Discovery of CAZYmes for cell surface glycan removal through metagenomics: Towards universal blood. 256th ACS National Meeting & Exposition, abstract # CARB 105