title: Enhancement of folates in plants through metabolic engineering.
abstract: Humans depend on plants as a major source of dietary folates. Inadequate dietary levels of the vitamin folate can lead to megaloblastic anemia, birth defects, impaired cognitive development, and increased risk of cardiovascular disease and cancer. The biofortification of folate levels in food crops is a target for metabolic engineering. Folates are synthesized de novo from pterins and para-amino benzoic acid, which are subsequently combined to form dihydropteroate, the direct precursor to dihydrofolate. We postulated that GTP cyclohydrolase-1, which catalyzes the first committed step in pterin biosynthesis, was a rate-limiting step in pterin synthesis in plants and, therefore, in folate synthesis. On this basis, we proposed that the expression of an unregulated bacterial GTP cyclohydrolase-1 in plants would increase pterin biosynthesis with a concomitant enhancement of folate levels. The folE gene encoding GTP cyclohydrolase-1 was cloned from Escherichia coli and introduced into Arabidopsis thaliana through plant transformation. The expression of bacterial GTP cyclohydrolase-1 in transgenic Arabidopsis resulted in a 1,250-fold and 2- to 4-fold enhancement of pterins and folates, respectively. These results helped to identify other potential factors regulating folate synthesis, suggesting ways to further enhance folate levels in food crops.
authors.affiliation: Donald Danforth Plant Science Center, 975 North Warson Road, St. Louis, MO 63132, USA.
authors.forename: Tahzeeba
authors.initials: T
authors.lastname: Hossain
authors.forename: Irwin
authors.initials: I
authors.lastname: Rosenberg
authors.forename: Jacob
authors.initials: J
authors.lastname: Selhub
authors.forename: Ganesh
authors.initials: G
authors.lastname: Kishore
authors.forename: Roger
authors.initials: R
authors.lastname: Beachy
authors.forename: Karel
authors.initials: K
authors.lastname: Schubert
mesh_terms: D017360:Arabidopsis / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D017931:DNA Primers; D005492:Folic Acid / Q000378:metabolism*; D005818:Genetic Engineering; D030821:Plants, Genetically Modified
chemical_list: D017931:DNA Primers; D005492:Folic Acid