Is specialized metabolite regulation specialized?

Recent technical and theoretical advances have generated an explosion in the identification of specialized metabolite pathways. In comparison, our understanding of how these pathways are regulated is relatively lagging. This and the relatively young age of specialized metabolite pathways has partly contributed to a default and common paradigm whereby specialized metabolite regulation is theorized as relatively simple with a few key transcription factors and the compounds are non-regulatory end-products. In contrast, studies into model specialized metabolites, such as glucosinolates, are beginning to identify a new understanding whereby specialized metabolites are highly integrated into the plants' core metabolic, physiological, and developmental pathways. This model includes a greatly extended compendium of transcription factors controlling the pathway, key transcription factors that co-evolve with the pathway and simultaneously control core metabolic and developmental components, and finally the compounds themselves evolve regulatory connections to integrate into the plants signaling machinery. In this review, these concepts are illustrated using studies in the glucosinolate pathway within the Brassicales. This suggests that the broader community needs to reconsider how they do or do not integrate specialized metabolism into the regulatory network of their study species.