ArticleThe Plant cell2021
The 5-formyl-tetrahydrofolate proteome links folates with C/N metabolism and reveals feedback regulation of folate biosynthesis.
Article in The Plant cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 33 citations in OpenAlex.
- Photorespiration is linked to DNA methylation by formate as a one-carbon source.Nature plants · 2026Article
- Foliar folic acid application enhances nitrogen assimilation and improves quality-related metabolites accumulation inFrontiers in plant science · 2026Article
- Changes of folate constituents and contents in pakchoi as affected by nitrate to ammonium ratio in nutrient solution under hydroponic conditions.Journal of Zhejiang University. Science. B · 2025Article
- Folate from probiotic bacteria and its therapeutic applications.Archives of microbiology · 2025Review
- Folate depletion impact on the cell cycle results in restricted primary root growth in Arabidopsis.Plant molecular biology · 2025Article
- Genome and transcriptome wide association study identify candidate genes regulating folate levels in maize.Frontiers in plant science · 2025Article
- Transcriptomic Insights: Phytogenic Modulation of Buffel Grass (Plants (Basel, Switzerland) · 2024Article
- The serine-glycine-one-carbon metabolic network orchestrates changes in nitrogen and sulfur metabolism and shapes plant development.The Plant cell · 2024Article
- Arabidopsis Root Development Regulation by the Endogenous Folate Precursor, Para-Aminobenzoic Acid, via Modulation of the Root Cell Cycle.Plants (Basel, Switzerland) · 2023Article
- Foxtail millet [Frontiers in nutrition · 2023Article
- Reduced γ-glutamyl hydrolase activity likely contributes to high folate levels in Periyakulam-1 tomato.Horticulture research · 2023Article
- Metabolic network changes during skotomorphogenesis inPlant direct · 2022Article
- B vitamin supply in plants and humans: the importance of vitamer homeostasis.The Plant journal : for cell and molecular biology · 2022Review
- Folate (vitamin B9) content analysis in bread wheat (Frontiers in nutrition · 2022Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Folates are indispensable for plant development, but their molecular mode of action remains elusive. We synthesized a probe, "5-F-THF-Dayne," comprising 5-formyl-tetrahydrofolate (THF) coupled to a photoaffinity tag. Exploiting this probe in an affinity proteomics study in Arabidopsis thaliana, we retrieved 51 hits. Thirty interactions were independently validated with in vitro expressed proteins to bind 5-F-THF with high or low affinity. Interestingly, the interactors reveal associations beyond one-carbon metabolism, covering also connections to nitrogen (N) metabolism, carbohydrate metabolism/photosynthesis, and proteostasis. Two of the interactions, one with the folate biosynthetic enzyme DIHYDROFOLATE REDUCTASE-THYMIDYLATE SYNTHASE 1 (AtDHFR-TS1) and another with N metabolism-associated glutamine synthetase 1;4 (AtGLN1;4), were further characterized. In silico and experimental analyses revealed G35/K36 and E330 as key residues for the binding of 5-F-THF in AtDHFR-TS1 and AtGLN1;4, respectively. Site-directed mutagenesis of AtGLN1;4 E330, which co-localizes with the ATP-binding pocket, abolished 5-F-THF binding as well as AtGLN1;4 activity. Furthermore, 5-F-THF was noted to competitively inhibit the activities of AtDHFR-TS1 and AtGLN1;4. In summary, we demonstrated a regulatory role for 5-F-THF in N metabolism, revealed 5-F-THF-mediated feedback regulation of folate biosynthesis, and identified a total of 14 previously unknown high-affinity binding cellular targets of 5-F-THF. Together, this sets a landmark toward understanding the role of folates in plant development.
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