Designer plants one step closer to growing low-cost medical, industrial proteins
By Krishna Ramanujan
Imagine if plants could be engineered to produce vaccines, pharmaceuticals, proteins and enzymes for medical, agricultural and industrial applications at a fraction of their current cost.
A new Cornell-led study describes a major advancement in the field, literally.
The market for such biologically derived proteins is forecast to reach $300 billion in the near future. Industrial enzymes and other proteins are currently made in large, expensive fermenting reactors, but making them in plants grown outdoorscould reduce production costs by three times.
Cornell and University of Illinois researchers have engineered plants capable of making proteins not native to the plant itself. The study describes the first successful rearing of such plants outdoors in the field, a necessity for economic viability, so they can be grown at large scales.
“We knew these plants grew well in the greenhouse, but we just never had the opportunity to test them out in the field,” said Beth Ahner, professor of biological and environmental engineering and senior author of “Field-grown tobacco plants maintain robust growth while accumulating large quantities of a bacterial cellulase in chloroplasts,” published July 8 in the journal Nature Plants. Jennifer Schmidt, a graduate student in Ahner’s lab, is a co-first author.
That opportunity came when University of Illinois plant biology professor Stephen Long obtained a permit from the U.S. Department of Agriculture to grow the genetically modified plants in the field.
Conventional wisdom suggested that the burden of asking plants to turn 20% of the proteins they have in their cells into something the plant can’t use would greatly stunt growth.
“When you put plants in the field, they have to face large transitions, in terms of drought or temperature or light, and they’re going to need all the protein that they have,” Ahner said. “But we show that the plant still is able to function perfectly normally in the field [while producing nonnative proteins]. That was really the breakthrough.”
Though more research is needed, lab experiments showed that when the plants have enough sun, water and fertilizer, they will increase their uptake of nutrients as needed to compensate for the extra protein load.
In the study, the researchers genetically modified tobacco plants to produce the cellulase protein Cel6A, an enzyme. In the science realm, tobacco is a heavily studied model plant that biologists use in research because so much is known about it. The production of Cel6A serves as a proof of principle, but in a practical sense, it belongs to a large group of related enzymes used in the manufacturing of modern laundry detergents; in the textile industry, such as in the softening of blue jeans and other fabrics; and in the processing of food and animal feed. Also, cheaper cellulases can greatly reduce the end cost of ethanol and other biomass-derived green products.
The genetic engineering was achieved by delivering DNA with instructions for making a desired protein into the chloroplasts of plants cells. The plants containing chloroplasts that adopt this DNA are then cultivated. Chloroplasts are the photosynthesizing organelles in plants and contain their own DNA. Plant cells cannot make their own chloroplasts but inherit them from each daughter cell during cell division.
This design helps prevent plants with designer proteins grown in the field from contaminating other tobacco plants and relatives through the spread of pollen, which is contained in the stamen, the male portion of the plant.
“One of the advantages of the technology that we’re using is that the chloroplasts in most crop plants are inherited through the maternal line, so the genes are not in the pollen,” Ahner said. “The pollen is one of the main concerns for dispersal to other transgenic crops.”
In future work, Schmidt is investigating how to get plants to consistently produce different types of proteins. “We’re trying to understand the basic biological mechanism that allows any protein to be accumulated” in a genetically modified plant, Ahner said.
Justin McGrath, a research scientist in Long’s lab, is a co-first author of the paper. Maureen Hanson, the Liberty Hyde Bailey Professor in the Department of Molecular Biology and Genetics, is a co-author.
The study was funded by the USDA.