Coordinate Regulation of Metabolite Glycosylation and Stress Hormone Biosynthesis by TT8 in Arabidopsis

Secondary metabolites play a key role in coordinating ecology and defense strategies of plants. Diversity of these metabolites arise by conjugation of core structures with diverse chemical moieties, such as sugars in glycosylation. Active pools of phytohormones, including those involved in plant stress response are regulated by glycosylation. While, much is known about glycosylation enzymes, we know little about their regulation or coordination with other biological processes. We characterized the flavonoid pathway transcription factor, TRANSPARENT TESTA 8 (TT8) in Arabidopsis thaliana, using an integrative 'omics strategy to provide a systems level understanding of the cellular machinery used to generate metabolite diversity by glycosylation. Metabolomics analysis of loss-of-function and inducible overexpression lines of TT8 showed that it coordinates glycosylation of not only flavonoids, but also nucleotides, thus, implicating TT8 in regulating pools of activated sugars. Transcriptome and promoter network analyses revealed that TT8 regulome included sugar transporters, sugar binding and sequestration proteins, and carbohydrate active enzymes. Interestingly, TT8 also affects brassinosteroid and jasmonic acid biosynthesis by directly binding to the promoters of key genes of these two pathways. This combined effect on metabolites glycosylation and stress hormones by TT8 overexpression lead to significant increase in tolerance towards multiple abiotic and biotic stresses. Conversely, loss of TT8 leads to increased sensitivity to these stresses. Thus, TT8 is an integrator of secondary metabolism and stress response.