Identification and biosynthesis of bioactive triterpenes from Calendula officinalis

Golubova, Daria (2025) Identification and biosynthesis of bioactive triterpenes from Calendula officinalis. Doctoral thesis, University of East Anglia.

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Abstract

Plants have been used in traditional medicine for centuries. In some cases, the therapeutic properties of medicinal plants have been attributed to specific metabolites, enabling their use as drugs in modern medicine. However, the exact molecule(s) responsible for the bioactivity of majority plant extracts remains unknown. Additionally, access to specific compounds is often hindered by their low abundance, presence in complex mixtures, or structural complexity, making chemical synthesis challenging. This thesis describes an investigation into the previously reported anti-inflammatory and wound-healing bioactivities of Calendula officinalis (pot marigold), a well-known medicinal plant. Previous studies suggested that the bioactivity of pot marigold floral extracts may be linked to an abundance of triterpene fatty acid esters (TFAEs). However, the literature has not definitively determined if molecules from this class are the most potent anti-inflammatory compounds present in the extracts. Further, little is known about the mechanism of action that underlines the bioactivity, or about the biosynthesis of these molecules. Thus, my research aimed to identify the key bioactive compound(s) in pot marigold extracts, investigate their mechanism of action, and to discover and characterise enzymes involved in their biosynthesis. This was achieved by integrating comparative metabolic profiling of Asteraceae species with bioactivity assays in model human cell lines, leading to the identification of faradiol and faradiol FAEs as key anti-inflammatory compounds in pot marigold extract. Following this, a combination of metabolomics, genomics, transcriptomics and transient expression in Nicotiana benthamiana enabled the identification and characterisation of the biosynthetic enzymes responsible for the production of these compounds. Finally, a method for gene silencing in pot marigold was developed, providing an additional tool for pathway characterisation. This work contributes to the discovery and sustainable production of plant-derived bioactive compounds, offering new opportunities for pharmaceutical applications.

Item Type:	Thesis (Doctoral)
Faculty \ School:	Faculty of Science > School of Biological Sciences
Depositing User:	Kitty Laine
Date Deposited:	03 Jun 2025 12:04
Last Modified:	03 Jun 2025 12:04
URI:	https://ueaeprints.uea.ac.uk/id/eprint/99386
DOI:

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