Folic acid and folates: the feasibility for nutritional enhancement in plant foods

Abstract

In mammalian and plant cells the folates play a key role in the methylation cycle and in the DNA biosynthesis cycle (in the de novo biosynthesis of purines and pyrimidines). Deficiency of folate in the diet is likely to result in a reduction in the capacity to synthesise DNA and maintain the usual rate of cell division. This most evidently results in the production of anaemia from folate deficiency due to a reduction in the biosynthesis of cells in the bone marrow. In addition it has been shown that high levels of plasma homocysteine occur which is an important risk factor in cardiovascular disease. Furthermore it has been shown that reduced maternal folate status is associated with the progressive increase in neural tube defects in infants. There is good evidence for folate deficiency in a considerable number of the population in developed countries, even where folate supplementation of foods is practised, and for a level of intake in excess of the recommended dietary allowance. This paper reviews the principal routes of folate biosynthesis in plants and the potential for increasing the levels of natural folates through conventional plant breeding and biotechnological means. The effect of the major food preservation processes on the levels of folates in plants is also reviewed. The current information about the bioavailability of folates from plant food sources, and how this might be improved, is also summarised. The important health benefits that would arise from increasing folate intake in the diet provide a strong incentive for considering how this might be achieved. © 2000 Society of Chemical Industry

Folate biofortification in tomatoes by engineering the pteridine branch of folate synthesis

“…T etrahydrofolate (THF) and its derivatives (collectively termed folates) are essential cofactors for the one-carbon transfer reactions needed to form methionine, serine, purines, and thymidylate (1,2). Whereas plants and microorganisms can synthesize folates, humans and other animals lack a complete folate synthesis pathway and so require a dietary supply.…”

“…Whereas plants and microorganisms can synthesize folates, humans and other animals lack a complete folate synthesis pathway and so require a dietary supply. For humans, this supply comes mostly from plant sources (2,3). Green leafy vegetables and legume seeds are folate-rich, but staple foods such as cereals, tubers, and many fruits are relatively poor in folate; related to this, folate intakes are seriously inadequate in poor countries and suboptimal even in rich ones (3)(4)(5).…”

“…A promising alternative strategy (biofortification) is to enhance the folate content of food organisms by metabolic engineering (2,8,9). The validity of this approach has been demonstrated in food-grade lactic acid bacteria, in which engineering tripled folate production (10).…”

“…The validity of this approach has been demonstrated in food-grade lactic acid bacteria, in which engineering tripled folate production (10). Because the plant folate synthesis pathway is now known (2,(11)(12)(13)(14)(15), folate engineering can be attempted with plants, and several groups have begun doing this (16)(17)(18)(19). We have chosen to engineer the folate pathway in tomatoes, in view of their worldwide importance as a food crop, their well developed molecular genetics, and their relatively low folate content (3,13).…”

Enhancement of folates in plants through metabolic engineering

“…Folates are synthesized de novo from pterins and paraaminobenzoic acid (PABA) by means of a multistep pathway (15)(16)(17), whereas pterins and PABA are synthesized from GTP and chorismate, respectively (Fig. 1).…”