Fortification of plant folate genes in rice

Tetrahydrofolate is a B vitamin that serves as a coenzyme critical in the methylation cycle and DNA synthesis. It has an important role in the pathogenesis of a broad spectrum of human disease including anemia, cardiovascular disease, thromboembolism, dementia and Alzheimers along with various cancers. Importantly low folate has been demonstrated to be a major cause of congenital neural tube defects (NTDs). Folate cannot be synthesized by vertebrates, consequently plant food is the primary source. Rice however, which provides half the world's population with 80 percent of their diets, is particularly low in folate. The production of a rice crop yielding high level folate would benefit not only the developing world, but also the developed world as a supplement to fortified wheat products, particularly as the number of persons avoiding wheat products is rising markedly. We have identified and isolated four genes essential to the production of folate from wheat, a cereal with higher endogenous folate levels than rice. These are guanosine triphosphate cyclohydrolase1 (GCH1); HPPK/DHPS (6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK), 7,8-dihydropteroate synthase (DHPS); 4-amino-4-deoxychorismate synthase (pABA) and tetrahydrofolypolyglutamate synthase (FPGS). Each of these will be transformed into rice plants either singly or in combination via particle bombardment. The use of wheat genes, a closely related cereal, should alleviate problems seen with introduction of genes from distantly related species where poor gene homology results in a less functional pathway in the host plant.