Terpenoid Biosynthesis and Metabolic Engineering in Plants

Terpenoids, also known as isoprenoids, constitute the largest class of specialised plant metabolites and fulfil roles in growth regulation, defence, pollinator attraction and environmental adaptation. Biosynthesis is organised around two central pathways: the cytosolic mevalonate (MVA) pathway and the plastidic 2-C-methyl-d-erythritol-4-phosphate (MEP) pathway, which together supply the universal C5 building blocks isopentenyl diphosphate and dimethylallyl diphosphate. Prenyltransferases condense these units into linear prenyl diphosphates of defined lengths, which are subsequently cyclised and modified by terpene synthases (TPS) and tailoring enzymes to yield mono-, sesqui-, diterpenoids and beyond. Metabolic engineering exploits gene discovery, heterologous expression, subcellular targeting and pathway balancing to enhance yields of high-value compounds such as artemisinin, taxol and aroma terpenoids. Advances in enzyme structure–function analysis, regulatory network elucidation and genome editing have enabled precise flux control, dynamic regulation under stress and de novo pathway assembly in microbial and plant chassis. These developments promise sustainable production of pharmaceuticals, flavours, fragrances and biofuels while deepening our understanding of pathway evolution, ecological interactions and stress resilience in plants.

Research from Nature Portfolio

Recent studies have revealed a dual role for the MEP pathway in both isoprenoid precursor synthesis and oxidative stress sensing. Accumulation of the cyclic intermediate methylerythritol cyclodiphosphate (MEcDP) under reactive oxygen species triggers signalling functions and may act as an antioxidant, suggesting that engineering MEP pathway flux can simultaneously enhance stress tolerance and terpenoid yield. Complementary work on isoprenyl diphosphate synthases has demonstrated that metal-ion-dependent changes in enzyme symmetry govern the relative production of geranyl and farnesyl diphosphate. By altering metal-binding sites, it is possible to redirect carbon flux toward distinct terpene classes, offering a biophysical strategy to fine-tune precursor supply and diversify downstream terpenoids in planta or in engineered microorganisms.

Terpenoid Biosynthesis and Metabolic Engineering in Plants publication trend

The graph below shows the total number of articles in terpenoid biosynthesis and metabolic engineering in plants across all publications each year (not limited to Nature Index journals).

Technical terms

Isopentenyl diphosphate (IPP): Universal five-carbon building block for terpenoid biosynthesis.

Dimethylallyl diphosphate (DMAPP): Isomeric partner of IPP that condenses in prenyltransferase reactions.

MEP pathway: Plastidic 2-C-methyl-d-erythritol-4-phosphate pathway supplying IPP and DMAPP in plants.

Mevalonate (MVA) pathway: Cytosolic route to IPP and DMAPP operating in eukaryotes and archaea.

Terpene synthase (TPS): Enzyme that cyclises prenyl diphosphates into diverse terpene scaffolds.

Metabolic engineering: The modification of metabolic pathways to increase production or generate novel compounds.

References

1. The methylerythritol phosphate pathway as an oxidative stress sense and response system. Nature Communications (2024).
2. Metal-dependent enzyme symmetry guides the biosynthetic flux of terpene precursors. Nature Chemistry (2023).
3. The genomes of medicinal skullcaps reveal the polyphyletic origins of clerodane diterpene biosynthesis in the family Lamiaceae. Molecular Plant (2023).
4. Terpene Synthases as Metabolic Gatekeepers in the Evolution of Plant Terpenoid Chemical Diversity. Frontiers in Plant Science (2019).
5. The complete functional characterisation of the terpene synthase family in tomato. New Phytologist (2020).