Biosynthesis and bioactivity of anti-inflammatory triterpenoids in Calendula officinalis

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 medi...

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Main Authors: D. Golubova, M. Salmon, H. Su, C. Tansley, GG Kaithakottil, G. Linsmith, C. Schudoma, D. Swarbreck, MA O’Connell, NJ Patron
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-62269-w
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author D. Golubova
M. Salmon
H. Su
C. Tansley
GG Kaithakottil
G. Linsmith
C. Schudoma
D. Swarbreck
MA O’Connell
NJ Patron
author_facet D. Golubova
M. Salmon
H. Su
C. Tansley
GG Kaithakottil
G. Linsmith
C. Schudoma
D. Swarbreck
MA O’Connell
NJ Patron
author_sort D. Golubova
collection DOAJ
description 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.
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spelling doaj-art-fee65dee9f5647afa1184be11380a1ad2025-08-20T03:05:14ZengNature PortfolioNature Communications2041-17232025-07-0116111810.1038/s41467-025-62269-wBiosynthesis and bioactivity of anti-inflammatory triterpenoids in Calendula officinalisD. Golubova0M. Salmon1H. Su2C. Tansley3GG Kaithakottil4G. Linsmith5C. Schudoma6D. Swarbreck7MA O’Connell8NJ Patron9Engineering Biology, Earlham Institute, Norwich Research ParkEngineering Biology, Earlham Institute, Norwich Research ParkEngineering Biology, Earlham Institute, Norwich Research ParkEngineering Biology, Earlham Institute, Norwich Research ParkEngineering Biology, Earlham Institute, Norwich Research ParkEngineering Biology, Earlham Institute, Norwich Research ParkEngineering Biology, Earlham Institute, Norwich Research ParkEngineering Biology, Earlham Institute, Norwich Research ParkSchool of Chemistry, Pharmacy and Pharmacology, University of East AngliaEngineering Biology, Earlham Institute, Norwich Research ParkAbstract 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.https://doi.org/10.1038/s41467-025-62269-w
spellingShingle D. Golubova
M. Salmon
H. Su
C. Tansley
GG Kaithakottil
G. Linsmith
C. Schudoma
D. Swarbreck
MA O’Connell
NJ Patron
Biosynthesis and bioactivity of anti-inflammatory triterpenoids in Calendula officinalis
Nature Communications
title Biosynthesis and bioactivity of anti-inflammatory triterpenoids in Calendula officinalis
title_full Biosynthesis and bioactivity of anti-inflammatory triterpenoids in Calendula officinalis
title_fullStr Biosynthesis and bioactivity of anti-inflammatory triterpenoids in Calendula officinalis
title_full_unstemmed Biosynthesis and bioactivity of anti-inflammatory triterpenoids in Calendula officinalis
title_short Biosynthesis and bioactivity of anti-inflammatory triterpenoids in Calendula officinalis
title_sort biosynthesis and bioactivity of anti inflammatory triterpenoids in calendula officinalis
url https://doi.org/10.1038/s41467-025-62269-w
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