Cucurbitacins in Plant-Insect Interactions: Biosynthesis, Regulation, Ecological Functions, and Prospects for Crop...

Cucurbitacins are highly oxygenated tetracyclic triterpenoids characterized by intense bitterness, substantial structural diversity, and important consequences for plant-herbivore interactions. Although best known from Cucurbitaceae, cucurbitacins and related cucurbitane-type metabolites also occur in phylogenetically distant herbaceous and woody plants. Genetic and biochemical studies have validated several core biosynthetic steps, including cucurbitadienol formation by oxidosqualene cyclases and subsequent modification by cytochrome P450 monooxygenases, acyltransferases, and glycosyltransferases. Tissue-preferential basic helix-loop-helix transcription factors constitute the best-characterized regulatory layer, whereas the evidence supporting accessory regulators, transporters, and environmental responses varies from functional validation to transcriptomic or genomic prediction. From the plant perspective, cucurbitacins deter feeding or impair performance in many generalist and non-adapted herbivores. By contrast, their use as host-recognition cues and feeding stimulants by specialist diabroticite beetles reflects evolved herbivore adaptations involving perception, tolerance, metabolism, or sequestration rather than a second defensive function of the plant trait. Herbivore-induced cucurbitacin accumulation has been demonstrated in particular systems, although its regulatory mechanisms and ecological generality remain unresolved. Unlike previous reviews centered primarily on cucurbitacin chemistry, pharmacological activity, or individual biosynthetic pathways, this review integrates evidence-graded pathway reconstruction and molecular regulation with taxonomic distribution, insect adaptation, domestication, and agroecological consequences. Mechanistically, this review traces how scaffold formation, oxidative tailoring, conjugation, tissue-specific regulation, and transport give rise to contrasting ecological outcomes through herbivore-specific perception, tolerance, metabolism, and sequestration. We conclude that uniformly increasing or eliminating cucurbitacins is unlikely to provide broadly effective crop resistance because either direction may favor a different herbivore group. Future priorities include functional validation of candidate genes, spatially resolved metabolite analysis, comparative investigation of non-cucurbit lineages, and field evaluation involving generalist and specialist herbivores, crop quality, and non-target organisms. These advances will support context-specific fruit-quality improvement, behavioral pest control, and integrated pest management strategies rather than cucurbitacin manipulation as a stand-alone resistance approach.