Protein manufacturers must deal with their own sort of assembly line reject: the misfolded protein. Manufacturers can avoid the problem of tangled, gummed up, and hence useless proteins by relying on relatively costly production technologies, or they can resort to refolding techniques. Refolding, however, can be a tricky business. It can also be expensive and time-consuming.

Protein manufacturers have struggled to find efficient means of recycling valuable proteins. Such techniques could, for example, reduce costs for cancer treatments, food production, and other segments of the $160 billion global biotechnology industry. One such technique, say researchers at the University of California, Irvine, and South Australia's Flinders University, may soon be in hand.

These researchers, led by Gregory Weiss, Ph.D., UCI professor of chemistry and molecular biology and biochemistry, report that they have figured out a way to unboil the egg white of a hen egg. The unlikely-sounding feat dramatically demonstrates a new protein-refolding process that works much faster than a conventional technique, a kind of molecular dialysis.

The conventional technique is often left to work overnight. It can, however, take up to four days. “The new process takes minutes,” Dr. Weiss asserted. “It speeds things up by a factor of thousands.”

The new process was described January 23 in ChemBioChem, in an article entitled, “Shear-Stress-Mediated Refolding of Proteins from Aggregates and Inclusion Bodies.”

“We report the application of shear stress in micrometer-wide, thin fluid films to refold boiled hen egg white lysozyme, recombinant hen egg white lysozyme, and recombinant caveolin-1,” wrote the authors. “Furthermore, the approach allowed refolding of a much larger protein, cAMP-dependent protein kinase A (PKA).”

To re-create a clear protein known as lysozyme once an egg has been boiled, Dr. Weiss and his colleagues added a urea substance that chews away at the whites, liquefying the solid material. That's half the process; at the molecular level, protein bits are still balled up into unusable masses.
For the other half of the process, the scientists confined the tiny bits of protein to thin, microfluidic films and subjected them to sheer stress by means of a high-powered vortex fluid device. The protein bits were forced back into untangled, proper form.

“Yes, we have invented a way to unboil a hen egg. We start with egg whites boiled for 20 minutes at 90 degrees Celsius and return a key protein in the egg to working order,” said Dr. Weiss. “It's not so much that we're interested in processing the eggs; that's just demonstrating how powerful this process is. The real problem is there are lots of cases of gummy proteins that you spend way too much time scraping off your test tubes, and you want some means of recovering that material.”

The authors of the ChemBioChem article added that their rapid refolding technique could “significantly shorten times, lower costs, and reduce waste streams associated with protein expression for a wide range of industrial and research applications.”

For example, pharmaceutical companies currently create cancer antibodies in expensive hamster ovary cells that do not often misfold proteins. The ability to quickly and cheaply re-form common proteins from yeast or E. coli bacteria could potentially streamline protein manufacturing and make cancer treatments more affordable. Industrial cheese makers, farmers, and others who use recombinant proteins could also achieve more bang for their buck.








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