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  5. Elucidation and functional characterization of the biosynthetic pathway of the natural sweetener phyllodulcin in Hydrangea macrophylla.

Elucidation and functional characterization of the biosynthetic pathway of the natural sweetener phyllodulcin in Hydrangea macrophylla.

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Resource type
Journal article
Creator (person)
Padmakumar Sarala, Goutham
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Engel, Frauke
Hartmann, Anja
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von Wirén, Nicolaus
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Hajirezaei, Mohammad-Reza
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Date published
April 9, 2026
Abstract
Among the various natural products found in Hydrangea species, the bioactive dihydroisocoumarin, phyllodulcin (PD) stands out as a non-caloric, high-intensity sweetener, which is up to 800 times sweeter than sucrose. Additionally, PD possesses medicinal properties and plays plant-specific roles in pathogen resistance and abiotic stress tolerance. However, the biosynthetic pathway of PD in Hydrangea has remained unexplored. To identify intermediates and candidate genes involved in the biosynthesis of PD, we first conducted a screening approach, in which 14 out of 182 different Hydrangea accessions were selected for their contrasting foliar concentrations of PD and closely related hydrangenol (HD). Analysis of phenylpropanoid pathway (PPP) metabolites showed that accessions of H. macrophylla with high PD levels displayed distinct metabolite profiles compared to those with low PD concentrations. Specifically, caffeic acid, ferulic acid, and their derivatives, such as scopolin, scopoletin, esculetin, and fraxetin, were predominant in accessions with low PD concentrations. Conversely, the metabolite levels of phenylalanine, umbelliferone, p-coumaric acid, naringenin, resveratrol, and thunbergiol C (Thn C) were higher in accessions producing more PD. Transcriptome analysis revealed differentially expressed genes involved in phenylpropanoid biosynthesis, flavonoid biosynthesis, and stilbene biosynthesis pathways that are crucial for PD biosynthesis. Moreover, the identification of cyclase and ketoreductase genes, which were upregulated in accessions with high PD, provided further evidence for the biosynthetic pathway leading to PD. Based on metabolite profiling and gene expression data, we propose a hypothetical biosynthetic pathway for PD.
Project(s)
Priority 5: Enhanced Partnerships
Funder
Funder nameAwards
Bundesministerium für Wirtschaft und Energie, Germany
Projekt DEAL
Open access funding
Journal title
Scientific Reports
Volume
16
Article number
12044
Publisher
Springer Science and Business Media LLC
Place of publication
Berlin/Heidelberg, Germany
eISSN
2045-2322
Date accepted
April 3, 2026
Official URL
https://doi.org/10.1038/s41598-026-47892-x
Related URL
https://www.nature.com/articles/s41598-026-47892-x
Rights statement
In Copyright
Licence
https://creativecommons.org/licenses/by/4.0/
DOI
10.1038/s41598-026-47892-x
Keywords
Natural sweeteners
Mass spectrometry
Metabolomics
Hydrangea
Natural product chemistry
Phyllodulcin
Transcriptomics
Additional information
IF = 3.9 (2024)
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