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SEEKING SAVINGS, SAFETY IN EXPRESSION OF PLANT PROTEINS
 

Iowa’s leaders have long recognized that the work of chemical engineers, plant geneticists, and associated researchers at Iowa State is critical if biotechnology is to be one of the pillars of the state’s economy in the 21st century.

In the vanguard of this drive throughout his career, Professor Charles Glatz and his associates are currently in the third year of a $432,000 USDA grant for the “Recovery and Purification of Recombinant Proteins from Plants for Therapeutics and Industrial Enzymes.”

Glatz’s current work is actually the fifth in a series of grants that date from 1994. Moving from the investigation of soybeans and then canola as mediums for gene expression, and working with industrial partners such as ProdiGene and Fibrogen, Glatz and his colleagues eventually settled on corn as the current preferred host for their investigations.

“It’s gotten to the point we can have plants produce foreign proteins of practical value,” Glatz observes. “And it’s just getting to where plants can produce high enough levels of those proteins to make it economically viable to do it that way.”

To date, researchers have developed recombinant proteins that serve as sweeteners, pharmaceutical enzymes to treat digestive disorders, and a replacement for gelatin made from animal byproducts. Making desired proteins, however, is just one challenge; removing contaminants so the proteins are actually suitable for their intended applications is another proposition altogether.

“Once you get the cell to do the hard part in making the protein,” Glatz says, “purification takes a bunch of steps and is quite costly—up to 80% of the cost. So what we’re trying to do in this process is to remove some of those obstacles before things get too far along—attack that processing cost once the plant produces it and by changing how the plant produces it.”

In this process, says Glatz, collaborators Paul Scott (USDA) and Professor Kan Wang of the ISU Department of Agronomy effect the transformation of the plant, preparing and targeting the same marker protein to different sites of the seed. Co-PI Larry Johnson, director of the Center for Crop Utilization and Research, then performs fractioning of the grain to separate germ, endosperm, and other elements, isolating the targeted protein for extraction. The process allows the team to determine the ideal host fraction of the seed for expression of a given protein.

While more closely integrating expression and purification may reduce overall costs, the process addresses key security concerns as well. There has been heated debate over the safety of transgenic crops, and as industrial production becomes imminent, measures to protect food crops from genetically altered varieties has assumed greater urgency.

“Growing transgenic corn for valuable new products when so much is now grown for traditional uses,” Glatz says, “has to be done in a way that’s not going to harm the traditional crop and, more challenging, that won’t be perceived as harming the traditional crop.”

Conducting initial grinding and fractionation of genetically-altered crops where they are raised, Glatz maintains, enables extraction of the purified protein further upstream in the production process, lessening the chance that viable genetically-altered seeds might enter and contaminate commodity grain marketing channels.

Regulation of this type of research activity is still evolving, Glatz notes, so it’s premature to imagine what the eventual scope of industrial production might be. Still, he says, as the science develops, the team anticipates looking at a variety of hosts besides corn that can best match the needs of industry for the production of specific proteins with responsible stewardship of the environment and food supply.