By tweaking an enzyme borrowed from a bacterium, researchers have taken a step closer to creating blood that is safe for transfusing to all people, regardless of their blood type — A, B, AB or O.
Compared with the unaltered enzyme, designated Sp3GH98, the engineered version is 170 times faster at chopping apart certain sugar-based markers found on blood cells, researchers report online April 14 in the Journal of the American Chemical Society. Those sugars are signals of blood type; severing them transforms blood cells into a generic blood type that could be used universally for life-saving transfusions.
The natural enzyme, which researchers swiped from the pneumonia-causing bacterium Streptococcus pneumonia, is innately good at shearing the sugar markers that define blood cells as type B. But slow slicing of type A markers has been a sticking point for creating universal blood.
Type A markers, like type B markers, are made of three sugars that jut from the outside of red blood cells. But type A markers are tricky to remove because they link to other sugars on the cells in four different ways. (Type B sugars attach in one way). Cleaving all four types of links is a slow, inefficient task when the natural enzyme is added to blood, says chemical biologist David Kwan of the University of British Columbia in Vancouver. For some natural enzymes, it would take either a lot of time or a lot of enzyme — milligrams or grams of enzyme to treat a pint of blood. Ideally, scientists would need only micrograms, Kwan says.
To hasten the process, Kwan and colleagues created a new method to introduce mutations into the parts of the enzyme responsible for sugar cutting. The researchers then screened the mutants for speedy cleavage of two of the four type A marker linkages.
The method is “really neat and important,” says glycobiologist Henrik Clausen of the University of Copenhagen. But, he says, the dangling sugars that remain on the cells could signal the human immune system to get rid of the blood cells. If this is the case, researchers would have to develop additional treatments to hide the lingering sugars.
Kwan says he and colleagues are still developing the strategy. Their next step will be to continue mutating the enzyme so it cleaves all four type A markers quickly.