Engineering tomatoes to produce vitamin D

 Scientists have used a novel way to modify tomato plants to have fruits rich in  a precursor to vitamin D

Li, J., Scarano, A., Gonzalez, N.M. et al. Biofortified tomatoes provide a new route to vitamin D sufficiency. Nat. Plants (2022). https://doi.org/10.1038/s41477-022-01154-6

Reading the pages of the World Sustainable Development Goals 2 (SDG2) — Eradicating Hunger — is depressing to say the least. According to the estimates made in 2020, nearly 690 million people, who make up close to 8.9% of the world’s population, are hungry. This number has increased by 60 million in the preceding five years. The index which was initially decreasing has started to rise since 2015. This does not portend well for the SDG2 which has as its target zero hunger by 2030, and the guess is, if this trend continues, that the world will have 840 million people affected by hunger by 2030.

There are various ramifications to hunger, and an important part of it is micronutrient malnutrition. This is a term used for diseases caused by deficiency of vitamins and minerals in the diet. This is particularly a problem in developing countries and the number of those suffering from this so-called invisible hunger is huge. Some methods of combating this are to provide micronutrient supplements in the form of tablets or capsules and to fortify food products such as flour or salt by enhancing micronutrients in them. There is also the route of genetically modifying plants to produce biofortified leaves and fruit which can be consumed to alleviate micronutrient hunger.

In this line, a paper in Nature Plants by Jie Li et al tries to address vitamin D deficiency by genetically modifying tomato (Solanum lycopersicum) plants so that the fruit contains a significant amount of provitamin D 3 which is a precursor from which humans can make vitamin D. Provitamin D 3 has the chemical name 7-dehydrocholesterol, or 7-DHC for short. Humans can synthesise Vitamin D from 7-DHC when they are exposed to ultraviolet B (UVB) light. Vitamin D is needed for a process known as calcium homeostasis which is the maintenance of constant concentration of calcium ions in the body. This is needed for, among other things, bone development and strength, and its deficiency is a cause of conditions such as rickets and osteoporosis.

Other diseases that are associated with vitamin D deficiency are cancer, Parkinson’s disease and dementia. Vitamin D 3 is present in fish and dairy products. Vegetarian diets are particularly deficient in Vitamin D.

The recommended intake of vitamin D is 15 microgram per day for children and 20 microgram per day for elders. This can be given through supplements or a careful exposure to sunlight, but there are various caveats for the latter. It is in this context that the work of J. Li et al is significant. The authors of the paper, published in Nature Plants, tweaked a recently discovered pathway in tomato plants to produce cholesterol and a substance called steroidal glycoalkaloid (SGA for short) using the CRISPR-Cas9 gene editing tool. This inhibits the conversion of 7-DHC to cholesterol and instead the former accumulates in the leaves, green and ripe fruits.

Usually, in untreated tomato plants, 7-DHC is present in leaves and to a lower extent in green fruit, but not in ripe fruit — which is the most consumed of the lot. The researchers showed that in their modified plants, the suppression of the activity of a particular gene, “led to substantial increases of 7-DHC levels in leaves and green fruit,” and, according to the paper, while levels of 7-DHC were lower in ripe fruits of the mutant, they remained high enough that if converted to Vitamin D 3 by shining UVB light, the amount in one tomato would be equivalent to that in two eggs or 28 grams of tuna, both of which are recommended sources of vitamin D. In addition, the researchers report that the mutants showed a reduction in their leaves of a substance called alpha-tomatine, and they comment that this may even be beneficial because of alpha-tomatine’s reported toxicant or antinutritional activity. Surprisingly, the cholesterol levels in both fruit and leaves of the mutants was higher that of the wild-type. This was despite having blocked the conversion of 7-DHC to cholesterol.