Planting the Seeds for Folate Enrichment
The body needs folate—a B vitamin—but can’t produce it. Getting too little folate during pregnancy can lead to anemia in a mom and birth defects for her baby. If other adults get too little of the vitamin, they may face increased vulnerability to vascular disease and cancer. In other words, people need to eat foods that give them plenty of folate, which includes dark green vegetables, beans, legumes, and fortified grains.
By tinkering with two genes that take part in folate production in tomato plants, researchers in Florida have found a way to make tomatoes a remarkably rich source of this valued nutrient. The team reports in the March 6 Proceedings of the National Academy of Sciences that its manipulations boosted folate concentrations in the fruit roughly 20-fold.
The altered tomatoes thus contain more folate per gram than any other food. In fact, a 100-gram serving of the new tomatoes would deliver 840 micrograms of the vitamin—more than double the recommended daily intake for adults and half-again what a pregnant woman should take to prevent a neural-tube birth defect in her baby.
Unfortunately, laments biochemist Andrew D. Hanson of the University of Florida, such genetically modified foods don’t appeal to most U.S. and European consumers. “That wasn’t clear when we started the project,” he says, but “now, it’s very clear.”
His colleague Jesse F. Gregory III, a food chemist, agrees. “Discussing how [the genetically engineered tomatoes] might be marketed is quite hypothetical, at least for decades.”
Nevertheless, Gregory suspects that public acceptance of genetically modified foods, including his group’s tomatoes, will grow. When the market is ready, he says, the team’s achievement will be there to exploit.
Making changes
A plant makes folate through chemical interactions among three natural chemicals: pteridine, p-aminobenzoate (PABA), and the amino acid glutamate.
Although most plants have no shortage of glutamate, Hanson says, the two other chemicals can be quite limited.
Several years ago, his team decided to try to boost folate in tomato plants by inserting a synthetic version of a gene from mice. It boosted the plants’ pteridine production 100-fold, but folate production only doubled. The bottleneck, Hanson’s group realized, was that PABA was still too limited.
“Think of these pathways [to folate] as two tributaries feeding into a river,” Hanson explains. “The first thing we did was engineer a dramatic increase in pteridine, one tributary of that river.” It wasn’t until the researchers inserted a PABA-boosting gene from a weed plant that the tomato had enough pteridine and PABA to more dramatically ramp up folate production.
Interestingly, the researchers found that the dually manipulated tomatoes continued to build their concentrations of folate throughout their maturation. That’s in sharp contrast to what tomatoes normally do. A conventional tomato develops about 0.5 parts per million (ppm) folate by the time it reaches full size but is still green. After that, the concentration doesn’t increase much. Fruits of the new transgenic version have about normal folate concentrations while green, but they then build to about 10 ppm when fully ripe.
The researchers chose tomatoes for their work mainly for convenience. An expert on tomato biology and engineering worked down the hall, Hanson notes, “so we had all of the skills needed to produce transgenic tomato plants.” It didn’t hurt, he says, that tomatoes are a major food crop and that their inherent acidity helps make any folate in them less likely to break down during transport and storage. Finally, the researchers had access to an experimental dwarf variety of the plant that grew quickly, so that many generations could be studied over relatively short periods.
In fact, Hanson says, because the biggest need for inexpensive folate fortification is in poor countries—especially in Africa and Asia—the goal for future folate-fortification projects will probably be “crops that are consumed in those countries as staples. Rice would be one target, as would be cereals like sorghum and maize, and sweet potatoes or other tuber crops.”
Hanson suspects that even these plants will need to be genetically modified to have big folate payoffs, because none of them naturally makes enough pteridine and PABA to be exploited by conventional cross-breeding.
New folate may be better absorbed
Folate is the name given to a family of related compounds with vitamin activity. What distinguishes one from another is the number of glutamate units that form a tail on the molecule.
Plants naturally make folate in versions containing one to seven glutamate units in their tails. However, among the transgenic tomatoes, Gregory notes, “the bulk of the folate has only one glutamate.” By contrast, unaltered tomato plants produced most of their folate with six glutamates.
Although there has been some inconsistency in the findings of research looking at how well folates with different-length glutamate tails are absorbed in the gut, Gregory notes that many studies have suggested that multiple-glutamate forms are 25 to 30 percent less absorbable than folate with a single-glutamate tail.
“So,” Hanson concludes, “it appears that if anything, our transgenic plants would be somewhat better in this regard.”
