I was published in Nature
Certain biological functions require essential nutrients; these are molecules that the body cannot produce itself and must be taken up through the diet. Folate is one of these essential nutrients and folate deficiency is a problem in many developing countries. Researchers at UGent recently created a genetically modified rice variety, which produces large amounts of folate in the grains and stabilizes the nutrient so that the nutritional value is preserved after storage. The results were published in the renowned journal Nature Biotechnology. This rice variety presents a viable solution for folate deficiency in countries where rice is a major component of their diet.
No folate, no growth
Folate, also known as vitamin B9, is an essential micronutrient for humans. It is present in many kinds of food such as leafy vegetables, meat and dairy products and is particularly abundant in spinach, asparagus, yeast and liver. Folate is an indispensible cofactor in methylation reactions and is necessary for the biosynthesis of DNA and protein building blocks: nucleotides and amino acids. During rapid growth and cell division, higher folate levels are necessary. In humans, this rapid growth and division of cells occurs during the developmental stages of life, such as pregnancy and infancy. During these stages there is an increased need for folate and is vital for proper development.
Folate deficiency can also have an influence on many body functions and can lead to certain kinds of anemias and liver diseases. For example, neurotransmitter synthesis is dependent on the presence of folate and a shortage has been linked to depression. If insufficient folate is taken up before and during pregnancy, this can cause several congenital malformations. The most notable of these are neural tube defects such as the widely known spina bifida. An increased uptake of folate can thus prevent these developmental complications during pregnancy.
Fighting hidden hunger
Worldwide, fortification of flour with folate is a standard procedure and is mandatory for at least one major cereal grain in 76 countries. Adding folate to food is a suitable strategy for tackling folate deficiency in a large population. For people who require additional folate in their diet, many drug stores provide folate-containing food supplements. Folate is a water-soluble vitamin, so there is little concern for toxicity as excess folate will be excreted from the body in the urine. Folate deficiency is mainly an issue in developing countries, where the diet is limited. In India, and large parts of Asia, rice forms the bulk of the food consumed and while it is rich in calories, rice contains little folate. For this reason, famine is not necessarily present but the lack of micronutrients in the diet creates a ‘hidden hunger’.
The research team led by Dominique Van Der Straeten tackled this problem and developed a rice variety, through metabolic engineering, with a 100-fold increased folate level compared to wild-type rice in 2007. Their latest study shows that 50% of the folate is lost after 4 months of storage. Vitamins are fragile molecules and are sensitive to environmental factors such as temperature, light, oxygen and humidity. This frailty creates a challenge: storage in humid and relatively warm conditions is unavoidable in many developing countries.
How to preserve vitamins
Van Der Straeten and her team very elegantly solved this problem using two strategies. The first was to create a complex between folate and folate-binding proteins (FBP), as this stabilizes the vitamin. FBPs have not yet been discovered in plant species but are known to be present in mammals. By expressing a synthetic FBP derived from cow milk FBP in the rice variety, the folate that is produced can be bound by FBP and conserved. A second approach was to overexpress the folylpolyglutamate synthetase enzyme (FPGS) in the folate synthesis pathway. By doing this, the negatively charged glutamate ‘tail’ of folate is extended. This enhances retention of folate in the cell and allows long-term conservation of rice grains without substantial vitamin loss. Combining both strategies resulted in the next generation of high-folate rice: a variety with 150-fold higher folate levels compared to wild-type plants with next to no nutritional loss after 4 months of preservation.
References
Blancquaert, Dieter, et al. “Improving folate (vitamin B9) stability in biofortified rice through metabolic engineering.” Nature biotechnology (2015).
(Photo by Roberto Faccenda, https://creativecommons.org/licenses/by-sa/2.0/legalcode)
