Getting to the root of protein production.

As scientists identify greater numbers of natural proteins that have medical and industrial use, they continue to search for efficient ways to produce the molecules in bulk. Investigators have induced bacteria to chum out extra proteins, cloned animals that secrete novel proteins in their milk, and engineered plants to deposit proteins of interest in leaves or seeds.

Now, a research team has made tomato plants that secrete desired proteins from their roots. When such plants are grown hydroponically--in a nutrient-containing solution rather than in soil--researchers can collect the protein of interest from the liquid with relative ease.

"This may really change the economics and feasibility of protein production in plants by allowing you to `milk' them in a way similar to milking a transgenic sheep or goat," says Ilya Raskin of Rutgers University in New Brunswick, N.J. He and his colleagues describe their new protein production technique in the May NATURE BIOTECHNOLOGY.

While roots are best known for drawing nutrients from the soil, Raskin notes that they also secrete various proteins, primarily to protect against bacteria and other disease agents. As scientists unraveled this secretion pathway, Raskin and his colleagues began to wonder if they could exploit it.

The investigators do so by changing the gene for any protein of interest. One alteration eliminates parts of the protein that signal a cell to retain the molecule. A second change adds a few amino acids that tell the cell to secrete the protein. The researchers also place the modified gene under the control of a DNA sequence that makes the gene active only in root cells. Finally, they insert the tailored gene into a tomato plant's genome.

Raskin's group made such modifications on three genes and induced tomato plant roots to secrete significant amounts of each gene's protein. "We haven't spent any time optimizing the system, and we're already getting respectable rates of production," says Raskin.

Tests on the proteins, none of which is of commercial interest, showed that the process didn't ruin their activity. The researchers are now introducing a gene into tomato plants to make their roots secrete a viral protein used in hepatitis B vaccines.

Collecting valuable proteins with this new technique wouldn't involve the harvesting of plants and the laborious, costly task of purifying the proteins from them, notes Robert L. Erwin of Biosource Technologies, a firm in Vacaville, Calif., that makes tobacco plants produce proteins in their leaves (SN: 1/30/99, p. 69). "You can harvest the protein [from the hydroponic solution] on a continual-flow basis. It would reduce what a lot of people have considered some of the disadvantages of transgenic plant protein production," he says.