title: Nicotianamine, a novel enhancer of rice iron bioavailability to humans.
abstract: BACKGROUND
  Polished rice is a staple food for over 50% of the world's population, but contains little bioavailable iron (Fe) to meet human needs. Thus, biofortifying the rice grain with novel promoters or enhancers of Fe utilization would be one of the most effective strategies to prevent the high prevalence of Fe deficiency and iron deficiency anemia in the developing world.
  
  
  RESULTS
  We transformed an elite rice line cultivated in Southern China with the rice nicotianamine synthase gene (OsNAS1) fused to a rice glutelin promoter. Endosperm overexpression of OsNAS1 resulted in a significant increase in nicotianamine (NA) concentrations in both unpolished and polished grain. Bioavailability of Fe from the high NA grain, as measured by ferritin synthesis in an in vitro Caco-2 cell model that simulates the human digestive system, was twice as much as that of the control line. When added at 1:1 molar ratio to ferrous Fe in the cell system, NA was twice as effective when compared to ascorbic acid (one of the most potent known enhancers of Fe bioavailability) in promoting more ferritin synthesis.
  
  
  CONCLUSIONS
  Our data demonstrated that NA is a novel and effective promoter of iron utilization. Biofortifying polished rice with this compound has great potential in combating global human iron deficiency in people dependent on rice for their sustenance.
authors.affiliation: State Key Laboratory of Plant Physiology and Biochemistry, College of Life Sciences, Zhejiang University, Hangzhou, China.
authors.forename: Luqing
authors.initials: L
authors.lastname: Zheng
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Cheng
authors.forename: Chunxiang
authors.initials: C
authors.lastname: Ai
authors.forename: Xinhang
authors.initials: X
authors.lastname: Jiang
authors.forename: Xiaoshu
authors.initials: X
authors.lastname: Bei
authors.forename: Ye
authors.initials: Y
authors.lastname: Zheng
authors.forename: Raymond P
authors.initials: RP
authors.lastname: Glahn
authors.forename: Ross M
authors.initials: RM
authors.lastname: Welch
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Miller
authors.forename: Xin Gen
authors.initials: XG
authors.lastname: Lei
authors.forename: Huixia
authors.initials: H
authors.lastname: Shou
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000235:genetics*; D001383:Azetidinecarboxylic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D001682:Biological Availability; D018556:Crops, Agricultural; D006801:Humans; D007501:Iron / Q000493:pharmacokinetics*; D012275:Oryza / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D030821:Plants, Genetically Modified; D011401:Promoter Regions, Genetic; D019076:Transgenes
chemical_list: C082893:nicotianamine; D001383:Azetidinecarboxylic Acid; D007501:Iron; D019883:Alkyl and Aryl Transferases; C118230:nicotianamine synthase