From stress perception to metabolite disposition: dynamic regulation of stilbene biosynthesis in plants

Stilbenes are inducible plant specialized metabolites, best exemplified by resveratrol, a phytoalexin that links environmental perception, defense responses, and phenylpropanoid resource allocation. Stilbene accumulation may be controlled at three mechanistically distinct levels: signaling cascades that connect environmental and hormonal cues to kinase-dependent activation; combinatorial transcriptional control, which governs the response amplitude and specificity of stilbene synthase (STS) genes; and branch selection together with product disposition, which shapes the final metabolic output. Within this framework, MYB and WRKY proteins serve as major transcriptional nodes as activators or repressors, yet their regulatory effects depend on combinatorial interactions, phosphorylation events, competitive promoter occupancy, and metabolic context. We explicitly distinguish strongly supported mechanisms, defined by genetic perturbation, direct target validation, and metabolite quantification from emerging models built primarily on transient expression assays or co-expression correlations. This distinction avoids equating regulators supported by disparate levels of experimental evidence, identifies the most robust principles governing pathway control, and highlights experiments required to turn descriptive associations into causal mechanistic models. We further highlight conceptual insights extending beyond stilbene metabolism to inducible specialized metabolism in general, and outline research priorities for comparative genetics, cell-resolved analysis, and predictive pathway engineering.