: An Upstart Resource for Cucurbitacin Production Offers Insights into the Origin of Plant Bitter () Gene Clusters.

Cucurbitacins, oxygenated tetracyclic triterpenoids that are found mainly in the Cucurbitaceae family, play essential roles as defensive compounds, serving as allomones against herbivores and pathogens and as signals for insect-parasite recognition. These compounds also exhibit various pharmacological effects. The biosynthesis of cucurbitacins is largely regulated by the bitter () gene, encoding an oxidosqualene cyclase, which catalyzes the conversion of 2,3-oxidosqualene into cucurbitadienol, a common precursor for cucurbitacin synthesis. Previous studies focused on uncovering the gene clusters in Cucurbitaceae, but their presence in other cucurbitacin-producing plants remained unexplored. Here, the evolutionary history of genes and their clusters were investigated in twenty-one plant genomes spanning three families based on chemotaxonomy. Nineteen genes were identified in fourteen Cucurbitaceae, four Begoniaceae, and one species. Phylogenetic analysis suggested that the genome of contained the earliest gene clusters in this dataset. Moreover, the genomic analysis revealed a conserved microsynteny of pivotal genes for cucurbitacin biosynthesis in Cucurbitaceae, while interspersed gene clusters were observed in Begoniaceae, indicating rearrangements during plant gene cluster formation. The bitter gene in was found to promote cucurbitadienol biosynthesis in the leaves of . This comprehensive exploration of plant genes and their clusters provides valuable insights into the genetic and evolutionary underpinnings of cucurbitacin biosynthesis. These findings offer prospects for a deeper understanding of cucurbitacin production and potential genetic resources for their enhancement in various plants.