Findings presented at the 256th ACS National Meeting and Exposition (19–23 August 2018; MA, USA) suggest donated blood can be made universal by utilizing enzymes found in the human gut. The research, carried out at the University of British Columbia (BC, Canada), identified a new family of enzymes reported to be 30 times more effective at removing red blood cell antigens than previously reported candidates.
“We have been particularly interested in enzymes that allow us to remove the A or B antigens from red blood cells,” commented Stephen Withers. “If you can remove those antigens, which are just simple sugars, then you can convert A or B to O blood.”
Adjusting donated blood to a common universal type has been pursued by scientists in recent years, however, they have been unsuccessful in finding efficient and selective enzymes that are safe and economical.
Enzyme candidates were assessed in collaboration with another lab at the University of British Columbia, using metagenomics to sample the genes of millions of microorganisms without the need to culture each species. E.coli was then used to select for DNA containing genes that code for enzymes to cleave sugar residues. The team utilized metagenomics to screen for new biocatalysts, instead of a means to learn about microbial ecology.
"This is a way of getting that genetic information out of the environment and into the laboratory setting and then screening for the activity we are interested in," remarked Withers.
Ultimately, the researchers found successful candidate enzymes in the microbiome of the human gut. Mucins, which are glycosylated proteins, line the gut wall and provide sugars to both serve as attachment points and feed gut bacteria that aid in digestion. Some mucin sugars were found to be similar in structure to antigens found on type A and B blood.
By identifying the enzymes bacteria use to remove sugars from mucin, the researchers found a novel family of enzymes that can remove red blood cell antigens, altering A- and B-type blood to the universal type-O.
The scientists are now working in collaboration with the Centre for Blood Research to validate the enzyme candidates and test them on a larger scale. Furthermore, Withers plans to stimulate natural evolution in the enzymes to create the most efficient enzyme for removing the antigens.
"I am optimistic that we have a very interesting candidate to adjust donated blood to a common type," concluded Withers.
"Of course, it will have to go through lots of clinical trials to make sure that it doesn't have any adverse consequences, but it is looking very promising."
Source: Withers SG. Discovery of CAZYmes for cell surface glycan removal through metagenomics: Towards universal blood. ACS National Meeting and Exposition 2018 (19–23 August; MA, USA)