Whale protein puts researchers on path to developing synthetic blood

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Whale myoglobin may hold the key to creating synthetic blood(Credit: Rice University)

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Researchers at Rice University have discovered that a protein found in whale meat may hold the key to developing synthetic blood. The protein, called myoglobin, allows marine mammals to remain submerged at great depths for up to two hours and has an ultra-stable structure that could one day allow for the manufacturing of a blood substitute using bacteria as biofactories.

The team, led by Rice University biochemist John Olson, is developing the synthetic blood in order to address a major problem in emergency medicine: the chronic shortage of whole blood. Currently, emergency services rely on donated blood for transfusions. When this isn't available, the only alternatives are serums and saline solutions. The problem is, whole blood has a very short shelf life, blood serum not much more, and saline solutions are good for little more than keeping the blood system topped up so the heart can keep working.

The goal of the Rice team is to use genetically-engineered bacteria to manufacture a molecule based on myoglobin, which is similar but simpler in structure to hemoglobin, the protein found in red blood corpuscles that allows blood to carry oxygen and makes corpuscles and blood red. The tricky bit is to find the right myoglobin to start off.

Hemoglobin works by bonding with oxygen in a way that's both chemical and physical. That is, the globin part of the molecule holds the heme group, which can change its shape, so it can unfold to catch oxygen molecules, then fold up again to seal them in a waterproof pocket.

Unfortunately, it's a protein so complex that it takes some major computing power to map its structure, which means that it's extremely difficult to synthesize outside the body.

Researchers George Phillips, Premila Samuel and John Olson at Rice University(Credit: Rice University)

Myoglobin is found in the muscle tissues of most species of marine mammals as well as humans. Its function is similar to hemoglobin, except it's found in muscle tissue, where it acts as a local oxygen reserve for quick access. In marine mammals, it's found in much higher quantities and gives whale meat its rich, dense color. Whale myoglobin is 60 times as stable as human myoglobin and doesn’t unfold readily. This allows whales and other marine mammals to store large quantities of it in their muscles, and indicates that the myoglobin could be manufactured on a large scale using bacteria.

"Whales and other deep-diving marine mammals can pack 10 to 20 times more myoglobin into their cells than humans can, and that allows them to 'download' oxygen directly into their skeletal muscles and stay active even when they are holding their breath," says Olson. "The reason whale meat is so dark is that it’s filled with myoglobin that is capable of holding oxygen. But when the myoglobin is newly made, it does not yet contain heme. We found that the stability of heme-free myoglobin is the key factor that allows cells to produce high amounts of myoglobin."

Using a new method that allows them to study myoglobin outside a living cell, the team looked at a heme-free form of myoglobin called an apoprotein or apomyoglobin. According to team member Premila Samuel, the structures of the different myoglobins are very similar, but differences in their amino acid sequences affect their stability. This becomes more obvious in the heme-free or "apo" versions, where chemicals that force them to unfold can be used to measure their stability. The more chemical needed, the more stable the molecule.

Put into practical terms, the Rice team found that whale myoglobin can be produced in 10 to 20 times the quantity of human or pig for the same effort. Though the outcome of the Rice team's work isn't yet a synthetic form of blood, they say that the methods they've developed will allow for faster screening of large libraries of hemoglobin variants without having to work with purified proteins in milligram quantities and is a major step toward identifying more stable recombinant hemoglobins that could one day be used in a blood substitute.

The team's findings were published in the Journal of Biological Chemistry.

The video below discusses the synthetic blood research.

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