ArticleProceedings of the National Academy of Sciences of the United States of America2004
Folate biofortification in tomatoes by engineering the pteridine branch of folate synthesis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 228 citations in OpenAlex.
- Reconfiguring biofortification strategies to transform food systems and address micronutrient deficiency of the 21st century.Journal of integrative plant biology · 2026Review
- Biological, dietetic and pharmacological properties of vitamin BNPJ science of food · 2025Review
- Exploration of folate and its derivatives in grains of wheat with different colors.Frontiers in genetics · 2025Article
- Review
- Comparative Transcriptome Analysis Reveals Mechanisms of Folate Accumulation in Maize Grains.International journal of molecular sciences · 2022Article
- Variation of vitamin B contents in maize inbred lines: Potential genetic resources for biofortification.Frontiers in nutrition · 2022Article
- Review
- Genetic and physiological regulation of folate in pak choi (Brassica rapa subsp. Chinensis) germplasm.Journal of experimental botany · 2020Article
- Comprehensive Vitamer Profiling of Folate Mono- and Polyglutamates in Baker's Yeast (Metabolites · 2020Article
- Plant Synthetic Metabolic Engineering for Enhancing Crop Nutritional Quality.Plant communications · 2020Review
- Genetic Engineering for Global Food Security: Photosynthesis and Biofortification.Plants (Basel, Switzerland) · 2019Review
- Improved folate accumulation in genetically modified maize and wheat.Journal of experimental botany · 2019Article
- Screening chemical modulators of benzoic acid derivatives to improve lipid accumulation inBiotechnology for biofuels · 2019Article
- From Central to Specialized Metabolism: An Overview of Some Secondary Compounds Derived From the Primary Metabolism for Their Role in Conferring Nutritional and Organoleptic Characteristics to Fruit.Frontiers in plant science · 2019Review
- Bioengineering of crop plants for improved tetrahydrofolate production.Bioengineered · 2018Review
- Toward Eradication of B-Vitamin Deficiencies: Considerations for Crop Biofortification.Frontiers in plant science · 2018Review
- Biofortified Crops Generated by Breeding, Agronomy, and Transgenic Approaches Are Improving Lives of Millions of People around the World.Frontiers in nutrition · 2018Review
- Genetic Engineering: A Possible Strategy for Protein-Energy Malnutrition Regulation.Molecular biotechnology · 2017Review
- Manipulation of Metabolic Pathways to Develop Vitamin-Enriched Crops for Human Health.Frontiers in plant science · 2017Review
- Metabolomics for Plant Improvement: Status and Prospects.Frontiers in plant science · 2017Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Plants are the main source of folate in human diets, but many fruits, tubers, and seeds are poor in this vitamin, and folate deficiency is a worldwide problem. Plants synthesize folate from pteridine, p-aminobenzoate (PABA), and glutamate moieties. Pteridine synthesis capacity is known to drop in ripening tomato fruit; therefore, we countered this decline by fruit-specific overexpression of GTP cyclohydrolase I, the first enzyme of pteridine synthesis. We used a synthetic gene based on mammalian GTP cyclohydrolase I, because this enzyme is predicted to escape feedback control in planta. This engineering maneuver raised fruit pteridine content by 3- to 140-fold and fruit folate content by an average of 2-fold among 12 independent transformants, relative to vector-alone controls. Most of the folate increase was contributed by 5-methyltetrahydrofolate polyglutamates and 5,10-methenyltetrahydrofolate polyglutamates, which were also major forms of folate in control fruit. The accumulated pteridines included neopterin, monapterin, and hydroxymethylpterin; their reduced forms, which are folate biosynthesis intermediates; and pteridine glycosides not previously found in plants. Engineered fruit with intermediate levels of pteridine overproduction attained the highest folate levels. PABA pools were severely depleted in engineered fruit that were high in folate, and supplying such fruit with PABA by means of the fruit stalk increased their folate content by up to 10-fold. These results demonstrate that engineering a moderate increase in pteridine production can significantly enhance the folate content in food plants and that boosting the PABA supply can produce further gains.
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