Mutabdzija-Nedelcheva, L. | Search bioRxiv

bioRxiv2026

Evolutionary origin of terpenoid biosynthesis in termites

Termites produce the most diverse array of terpenoids among metazoans, comprising over 200 structures. However, their biosynthesis has not yet been elucidated. Here, we identify a gene family which arose through the duplication of geranylgeranyl pyrophosphate synthase in the common ancestor of Neoisoptera, the terpene-producing termite lineage. We functionally characterized several proteins from this family as terpene synthases generating biologically relevant sesqui-and diterpenes. These include the queen pheromone (3R,6E)-nerolidol in Embiratermes neotenicus and the precursor of polycyclic defensive diterpenes (E,E,E)-neocembrene in Nasutitermes takasagoensis. We explore transposable element-mediated genomic mechanisms and selection pressures acting in the evolution of this gene family and report an amino acid site crucial for cyclization capacity as well as the enantiospecificity of the characterized enzymes. We conclude that we have identified an enzyme family underlying the remarkable richness of termite terpenoids, which likely contributed to the ecological success of Neoisoptera.

biochemistry↗

bioRxiv2025

Entry Steps in the Biosynthetic Pathway to DiterpenoidAlkaloids in Delphinium grandiflorum and Aconitum plicatum

Both the terpenoid and alkaloid classes of specialized metabolites have received considerable attention for their wide range of practical applications, however, few examples have been identified of these classes intersecting. The diterpenoid alkaloids are one such example of nitrogen-containing terpenoids which are found throughout many independent plant lineages, but primarily within the Aconitum (Wolfs-Bane) and Delphinium (Larkspur) genera. While there is considerable interest in these compounds for their wide range of bioactivities, their structural complexity often precludes their production through chemical synthesis, and little progress has been made towards elucidation of their biosynthetic pathways. Here, we employ a comparative transcriptomics approach to identify six enzymatic steps in the biosynthesis of atisinium, conserved across both Delphinium grandiflorum and Aconitum plicatum. Key to this pathway is a reductase which selectively incorporates ethanolamine over ethylamine into the diterpenoid scaffold. While the majority of diterpenoid alkaloids contain an ethylamine moiety, we demonstrate through isotope labeling in Aconitum callus cultures and a computational metabolomics approach that ethanolamine is, unintuitively, the preferred source of nitrogen for these metabolites. Identification of these enzymes and production of a key intermediate in a heterologous host paves the way for biosynthetic production of this group of metabolites with promise for medicinal applications.

biochemistry↗