Directing biosynthesis of bioactive triterpenes for pharmaceutical applications

Lead Research Organisation: University of East Anglia
Department Name: Graduate Office


The triterpenes are one of the largest and most diverse classes of plant natural products, with many useful biological properties. Some naturally occurring triterpenes have weak anti-inflammatory activity and are promising drug leads. Synthetic derivatives with improved activity have been generated but selective functionalisation of triterpene scaffolds using conventional chemistry is problematic, and the modifications made were limited. Phase three clinical trials of the best known of these synthetic triterpenes, bardoxolone methyl, were recently terminated because of side effects.
Recent advances in triterpene biosynthesis are now opening up new opportunities to systematically direct biosynthesis and modification of different triterpene scaffolds using enzymes, making it possible to understand for the first time the relationship between triterpene structure and function, and the features that determine potency and selectivity. This project exploits an innovative synthetic biology approach for quick and easy biosynthesis of novel triterpenes in a transient plant expression system. Triterpene analogs will be evaluated for anti-proliferative and anti-inflammatory activity, and the underlying signalling pathways and targets investigated. Structure activity relationship analysis will determine the specific moieties necessary for bioactivity and inform the further generation of structurally related compounds.


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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M011216/1 01/10/2015 30/09/2023
2059991 Studentship BB/M011216/1 01/10/2018 30/09/2022 Rebecca Casson