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ToolsGolubova, Daria, Salmon, Melissa, Su, Honghao, Tansley, Connor, Kaithakottil, Gemy George, Linsmith, Gareth, Schudoma, Christian, Swarbreck, David, O'Connell, Maria A. and Patron, Nicola J. (2025) Biosynthesis and bioactivity of anti-inflammatory triterpenoids in Calendula officinalis. Nature Communications, 16. ISSN 2041-1723
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Abstract
Plants have been central to traditional medicine for millennia, yet the precise metabolites responsible for their therapeutic properties often remain unidentified. In this work, we investigate the reported anti-inflammatory properties of Calendula officinalis (pot marigold), an ancient medicinal herb. We confirm C16-hydroxylated triterpenoids as key contributors to the anti-inflammatory activity of C. officinalis floral extracts and uncover a mechanism by which they act in modulating interleukin 6 release. Through biosynthetic pathway elucidation, we demonstrate that the oxidosqualene synthase catalysing the first committed step emerged early in Asteraceae evolution and identify residues governing product specificity. Further, we functionally characterise cytochrome P450s and acyltransferases responsible for downstream modifications. By reconstructing the complete biosynthetic pathway in the plant chassis Nicotiana benthamiana, we provide a basis for the future bioproduction of the anti-inflammatory components. Our work highlights how integrated studies of bioactivity and biosynthesis can unlock the therapeutic potential of medicinal plants.
| Item Type: | Article |
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| Additional Information: | Data availability: The assembled genome of C. officinalis generated in this study is available under accession number GCA_964273985.1 [https://www.ncbi.nlm.nih.gov/datasets/genome/GCA_964273985.1/]. The functional annotation of the C. officinalis genome and transcriptome assemblies of C. officinalis and C. arvensis are available at https://doi.org/10.5281/zenodo.13869958. Reads are available under accession numbers: PRJEB80524; [https://www.ebi.ac.uk/ena/browser/view/PRJEB80524] (C. officinalis) and PRJEB80545; [https://www.ebi.ac.uk/ena/browser/view/PRJEB80545] (C. arvensis). Plasmids are available at Addgene (227509-227578). Differential gene expression data, GC-MS data, LC-MS data, and NMR data are available at https://doi.org/10.5281/zenodo.13869958. Funding information: We gratefully acknowledge the support of the Biotechnology and Biological Sciences Research Council (BBSRC), part of UK Research and Innovation (UKRI) for funding via grants BB/W014173/1 and the Earlham Institute strategic programme grant, Decoding Biodiversity (BBX011089/1) and its constituent work package (BBS/E/ER/230002B). Part of this work was delivered by Transformative Genomics, a BBSRC-funded National Bioscience Research Infrastructure (BBS/E/ER/23NB0006). DG is supported by a scholarship from the John Innes Foundation; HS is supported by a BBSRC NRP-DTP scholarship (BB/T008717/1 Project No. 2578291). |
| Faculty \ School: | Faculty of Science Faculty of Science > School of Chemistry, Pharmacy and Pharmacology |
| UEA Research Groups: | Faculty of Science > Research Groups > Molecular and Tissue Pharmacology |
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| Depositing User: | LivePure Connector |
| Date Deposited: | 08 Sep 2025 10:30 |
| Last Modified: | 09 Sep 2025 08:30 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/100296 |
| DOI: | 10.1038/s41467-025-62269-w |
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