Vitamin D is an essential element for bones to process calcium, but it is not abundant in nature. The compound is primarily generated through the sun’s action on the skin. In its absence, fish oil, the liver of some animals and eggs are some of the few alternatives in the human diet. Now, a group of researchers has managed to make tomatoes produce as much vitamin D as the amount contained in two eggs, using a genetic modification technique. This is good news for vegans and for the more than one billion people who are deficient in the essential micronutrient.
Vitamin D is a hormone resulting from the action of medium wave ultraviolet rays (UVB) on human skin. This action converts a substance called 7-dehydrocholesterol (7-DHC), a precursor to cholesterol, into the vitamin. 7-DHC is present in tomato leaves and in green tomatoes. But, as the fruit matures, it is lost. Five years ago, it was discovered that the plant has two metabolic pathways for 7-DHC. One is used to produce defenses against pathogens. But the other, for unknown reasons, is not used.
Researchers from centers in several countries have used this second route to activate the production of 7-DHC, also called provitamin D3. The main author of the study, Cathie Martin, a scientist at the John Innes Centre, a British horticultural research institute, explains the process: “Provitamin D3 is synthesized in the tomato as an intermediate in the production of cholesterol and steroidoglycyl alkaloids [substances that act against pathogens]. We removed the activity of the enzyme that converts 7-DHC to cholesterol, which allowed 7-DHC to accumulate in high amounts in the leaves, but also in higher levels in green fruit and even ripe fruit.” To deactivate this enzyme, the scientists used the CRISPR genetic modification technique.
The next thing they did was to recover a natural process. By passing leaves and fruits through UVB rays, they converted 7-DHC into vitamin D. The amounts were very significant and never before detected in a vegetable. The leaves reached a concentration of 200 micrograms per gram of leaf. In the fruit, the amounts are smaller: 0.3 micrograms per gram in green ones and 0.2 in ripe ones. But a tomato would be enough to get between 20% and 30% of the daily vitamin D that humans need. The study’s authors believe that greater exposure to ultraviolet rays, including in the process of drying tomatoes in the sun, would increase the concentration.
When altering a metabolic pathway that, among other things, is involved in the generation of hormones, it is key to discern whether development or defenses are affected. “In other species, deletion of the gene that encodes 7-delta sterol reductase [the enzyme that converts 7-DHC into cholesterol] affects plant growth because this enzyme is necessary for the biosynthesis of brassinosteroids, a plant hormone that it intervenes in several development processes, especially height,” recalls Martin. In fact, investigations with lettuce or arabidopsis, the base plant of vegetable research, showed that blocking this route caused them to grow almost like bonsai. Tomatoes’ advantage is that they have a double pathway. “In Solanaceae (tomato, potato, aubergine and pepper) there is a second gene that specifically synthesizes cholesterol that is not necessary for the synthesis of brassinosteroids. That is what we eliminated so that our plants would not remain dwarfed.”
“The leaves, now a waste, could be a source of vitamin D”Gloria Torres Cortés, head of research and development of pre and probiotic products at the MAAVI Innovation Center of Kimitec
Gloria Torres Cortés, head of research and development of pre- and probiotic products at the MAAVI Innovation Center of the Kimitec biotechnology company, highlights that the challenge remains to increase the concentration of 7-DHC. “The leaves, which are currently treated as waste, could be a source of vitamin D. In addition, the strategy could be improved if other plants were edited [with CRISPR],” says the scientist, who has not participated in the study. The same method could be used to make other nightshades, such as peppers or aubergines, also generate the provitamin.
José Blanca, a genetics professor at the Polytechnic University of Valencia, is an expert in the history and genetics of tomatoes. “The new CRISPR technology makes it possible to create mutants with unprecedented simplicity. This has allowed them to create mutant tomatoes for a key enzyme in the production of defense compounds, which effectively now produces and accumulates vitamin D,” he says.
But Blanca doubts that this advance will come out of the laboratories soon. “In Europe, and especially in Spain, vitamin D deficiency in the population is quite common, so these tomatoes, or other vegetables or fruits in which the same is done, could be a good public health tool. Unfortunately, this will be difficult to achieve without a change in legislation because it is currently almost impossible to produce CRISPR-bred varieties in Europe due to anti-GMO legislation.”