ArticleScientific reports2026
Elucidation and functional characterization of the biosynthetic pathway of the natural sweetener phyllodulcin in Hydrangea macrophylla.
Article in Scientific reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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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.
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