Biosynthesis and Biological Activity of Sesquiterpene Lactones

Sesquiterpene lactones are a diverse class of plant-derived terpenoids characterised by a fifteen-carbon backbone and a γ-lactone ring. Biosynthesis commences with the universal precursor farnesyl pyrophosphate, which undergoes cyclisation by sesquiterpene synthases to yield hydrocarbon scaffolds such as germacrene A. Subsequent oxidation steps, chiefly catalysed by cytochrome P450 monooxygenases, introduce hydroxyl groups that facilitate intramolecular lactone formation. These transformations often occur in specialised tissues—trichomes, latex canals or glandular hairs—under tight developmental and environmental control. Beyond their ecological role in deterring herbivores and pathogens, sesquiterpene lactones exhibit a broad spectrum of bioactivities, including anti-inflammatory, antimalarial, cytotoxic and antimicrobial effects. Artemisinin, the antimalarial lead from Artemisia spp., exemplifies their pharmaceutical significance, while certain guaianolides and eudesmanolides inspire novel therapeutic leads. Advances in genome editing and metabolomics have begun to unravel regulatory networks driven by signalling molecules such as methyl jasmonate, enabling pathway engineering for enhanced yields and tailored bioactivity.

Research from Nature Portfolio

Metabolomic profiling and gene expression analyses in a medicinal Andean species have illuminated how developmental stage and environmental cues jointly govern sesquiterpene lactone accumulation. An integrative study revealed that metabolic diversity rises with plant age, while external factors modulate specific biosynthetic branches. Correlations between transcript levels of key synthases and oxidases and the relative abundance of over forty metabolites underscored a nuanced regulatory interplay. These insights provide a framework for dissecting transcriptional and post-transcriptional controls in sesquiterpene lactone biosynthesis.

Biosynthesis and Biological Activity of Sesquiterpene Lactones publication trend

The graph below shows the total number of articles in biosynthesis and biological activity of sesquiterpene lactones across all publications each year (not limited to Nature Index journals).

Technical terms

Farnesyl pyrophosphate (FPP): The universal C15 isoprenoid precursor for sesquiterpene biosynthesis.

Sesquiterpene lactone: A class of terpenoid compounds featuring a γ-lactone ring, often with bioactive properties.

Cytochrome P450 monooxygenase: A family of heme-containing enzymes that introduce oxygen functionalities essential for lactone formation.

Germacrene A acid: A central intermediate in many sesquiterpene lactone pathways formed by oxidation of germacrene A.

CRISPR/Cas9: A genome editing technology employed to disrupt specific genes and elucidate pathway function.

References

1. Lactucin Synthase Inactivation Boosts the Accumulation of Anti-inflammatory 8‑Deoxylactucin and Its Derivatives in Chicory (Cichorium intybus L.). Journal of Agricultural and Food Chemistry (2023).
2. Identification and characterization of CYP71 subclade cytochrome P450 enzymes involved in the biosynthesis of bitterness compounds in Cichorium intybus. Frontiers in Plant Science (2023).
3. Sesquiterpene Lactones – Insights into Biosynthesis, Regulation and Signalling Roles. Critical Reviews in Plant Sciences (2024).
4. Metabolomic and gene expression approaches reveal the developmental and environmental regulation of the secondary metabolism of yacón (Smallanthus sonchifolius, Asteraceae). Scientific Reports (2019).