{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T14:10:28Z","timestamp":1784902228095,"version":"3.55.0"},"reference-count":49,"publisher":"National Academy of Sciences","issue":"14","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2004,4,6]]},"abstract":"<jats:p>\n                    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\n                    <jats:italic>de novo<\/jats:italic>\n                    from pterins and\n                    <jats:italic>para<\/jats:italic>\n                    -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\n                    <jats:italic>folE<\/jats:italic>\n                    gene encoding GTP cyclohydrolase-1 was cloned from\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    and introduced into\n                    <jats:italic>Arabidopsis thaliana<\/jats:italic>\n                    through plant transformation. The expression of bacterial GTP cyclohydrolase-1 in transgenic\n                    <jats:italic>Arabidopsis<\/jats:italic>\n                    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.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0401342101","type":"journal-article","created":{"date-parts":[[2004,3,25]],"date-time":"2004-03-25T08:18:00Z","timestamp":1080202680000},"page":"5158-5163","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":121,"title":["Enhancement of folates in plants through metabolic engineering"],"prefix":"10.1073","volume":"101","author":[{"given":"Tahzeeba","family":"Hossain","sequence":"first","affiliation":[{"name":"Donald Danforth Plant Science Center, 975 North Warson Road, St. Louis, MO 63132; Friedman School of Nutrition and Policy, Tufts University, 711 Washington Street, Boston, MA 02111; and Dupont Agriculture and Nutrition, Box 88940, St. Louis, MO 63188"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irwin","family":"Rosenberg","sequence":"additional","affiliation":[{"name":"Donald Danforth Plant Science Center, 975 North Warson Road, St. Louis, MO 63132; Friedman School of Nutrition and Policy, Tufts University, 711 Washington Street, Boston, MA 02111; and Dupont Agriculture and Nutrition, Box 88940, St. Louis, MO 63188"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Selhub","sequence":"additional","affiliation":[{"name":"Donald Danforth Plant Science Center, 975 North Warson Road, St. Louis, MO 63132; Friedman School of Nutrition and Policy, Tufts University, 711 Washington Street, Boston, MA 02111; and Dupont Agriculture and Nutrition, Box 88940, St. Louis, MO 63188"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ganesh","family":"Kishore","sequence":"additional","affiliation":[{"name":"Donald Danforth Plant Science Center, 975 North Warson Road, St. Louis, MO 63132; Friedman School of Nutrition and Policy, Tufts University, 711 Washington Street, Boston, MA 02111; and Dupont Agriculture and Nutrition, Box 88940, St. Louis, MO 63188"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Beachy","sequence":"additional","affiliation":[{"name":"Donald Danforth Plant Science Center, 975 North Warson Road, St. Louis, MO 63132; Friedman School of Nutrition and Policy, Tufts University, 711 Washington Street, Boston, MA 02111; and Dupont Agriculture and Nutrition, Box 88940, St. Louis, MO 63188"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karel","family":"Schubert","sequence":"additional","affiliation":[{"name":"Donald Danforth Plant Science Center, 975 North Warson Road, St. Louis, MO 63132; Friedman School of Nutrition and Policy, Tufts University, 711 Washington Street, Boston, MA 02111; and Dupont Agriculture and Nutrition, Box 88940, St. Louis, MO 63188"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2004,3,24]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(91)90133-A"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/71.5.1295s"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/71.4.859"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.281.17.1632"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199212243272602"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/71.4.993"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199502023320511"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1996.03530480035037"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-129-7-199810010-00002"},{"key":"e_1_3_2_10_2","first-page":"10","volume":"11","year":"1997","unstructured":"Smaglik, P. 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