Biosynthesis of redox-active metabolites in response to iron deficiency in plants


Iron is an essential but poorly bioavailable nutrient because of its low solubility, especially in alkaline soils. Here, we describe the discovery of a previously undescribed redox-active catecholic metabolite, termed sideretin, which derives from the coumarin fraxetin and is the primary molecule exuded by Arabidopsis thaliana roots in response to iron deficiency. We identified two enzymes that complete the biosynthetic pathway of fraxetin and sideretin. Chemical characterization of fraxetin and sideretin, and biological assays with pathway mutants, suggest that these coumarins are critical for iron nutrition in A. thaliana. Further, we show that sideretin production also occurs in eudicot species only distantly related to A. thaliana. Untargeted metabolomics of the root exudates of various eudicots revealed production of structurally diverse redox-active molecules in response to iron deficiency. Our results indicate that secretion of small-molecule reductants by roots may be a widespread and previously underappreciated component of reduction-based iron uptake.

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Fig. 1: Metabolomics of T-DNA-insertion lines and heterologous gene expression reveal the sideretin biosynthetic pathway in A. thaliana.
Fig. 2: Chemical characterization of the iron-mobilization capacity of coumarins.
Fig. 3: Phenotypic characterization and complementation assays for s8h, cyp82C4, and other mutants under conditions of low iron availability.
Fig. 4: Phylogenetic distribution of sideretin-pathway enzyme orthologs and iron-deficiency-induced small-molecule exudation in various plants.
Fig. 5: Model for soil iron uptake in A. thaliana.


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This work was supported by US National Institutes of Health grant DP2 AT008321 and an HHMI–Simons Faculty Scholar Award to E.S.S. and by a grant from the Deutsche Forschungsgemeinschaft to N.v.W. (WI1728/21-1). J.R. was supported by an NIH Biotechnology Training Grant (T32 GM008412-20). We thank N. Schmid, J. Fuge, A. Bieber, H. Nierig, and M. Voges for valuable discussions and help with experiments; S. Elliott for advice on redox potential measurements; S. Fendorf for helpful discussions on rhizosphere iron; M. Kevin Brown and J. Du Bois for suggestions for chemical synthesis of sideretin; and T. Veltman for help with cyclic voltammetry measurements. We thank C. Curie (CNRS, IBIP, Montpellier) and M. B. Mudgett (Stanford University) for providing seeds.

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J.R., R.F.H.G., N.v.W., and E.S.S. designed experiments. J.R., R.F.H.G., and E.C. performed experiments. I.M. isolated homozygous T-DNA-insertion line cyp82C4-2. J.R., R.F.H.G., E.C., N.v.W., and E.S.S. analyzed data. J.R., R.F.H.G., N.v.W., and E.S.S. wrote the paper.

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Correspondence to Elizabeth S. Sattely.

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Rajniak, J., Giehl, R.F.H., Chang, E. et al. Biosynthesis of redox-active metabolites in response to iron deficiency in plants. Nat Chem Biol 14, 442–450 (2018).

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