title: Coordinate Regulation of Metabolite Glycosylation and Stress Hormone Biosynthesis by TT8 in Arabidopsis.
abstract: Secondary metabolites play a key role in coordinating ecology and defense strategies of plants. Diversity of these metabolites arises 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 also regulated by glycosylation. While much is known about the enzymes involved in glycosylation, we know little about their regulation or coordination with other processes. We characterized the flavonoid pathway transcription factor TRANSPARENT TESTA8 (TT8) in Arabidopsis (Arabidopsis thaliana) using an integrative omics strategy. This approach provides a systems-level understanding of the cellular machinery that is used to generate metabolite diversity by glycosylation. Metabolomics analysis of TT8 loss-of-function and inducible overexpression lines showed that TT8 coordinates glycosylation of not only flavonoids, but also nucleotides, thus implicating TT8 in regulating pools of activated nucleotide sugars. Transcriptome and promoter network analyses revealed that the TT8 regulome included sugar transporters, proteins involved in sugar binding and sequestration, and a number of carbohydrate-active enzymes. Importantly, TT8 affects stress response, along with brassinosteroid and jasmonic acid biosynthesis, by directly binding to the promoters of key genes of these processes. This combined effect on metabolite glycosylation and stress hormones by TT8 inducible overexpression led to significant increase in tolerance toward multiple abiotic and biotic stresses. Conversely, loss of TT8 leads to increased sensitivity to these stresses. Thus, the transcription factor TT8 is an integrator of secondary metabolism and stress response. These findings provide novel approaches to improve broad-spectrum stress tolerance.
authors.affiliation: Metabolites Biology Lab, Department of Biological Sciences, National University of Singapore, Singapore 117543 (A.R., S.U., M.R., L.B.K., J.A.S.B., S.S.);Synthetic Biology Research Consortium (A.R., S.S.) and Singapore Centre for Environmental Life Science Engineering (S.U., S.S.), National University of Singapore, Singapore 117456;NUS Environmental Research Institute, National University of Singapore, Singapore 117411 (S.U., M.R., L.B.K., S.S.); andSingapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, Singapore 637551 (S.S.).
authors.forename: Amit
authors.identifier: 0000-0002-5715-8541
authors.initials: A
authors.lastname: Rai
authors.affiliation: Metabolites Biology Lab, Department of Biological Sciences, National University of Singapore, Singapore 117543 (A.R., S.U., M.R., L.B.K., J.A.S.B., S.S.);Synthetic Biology Research Consortium (A.R., S.S.) and Singapore Centre for Environmental Life Science Engineering (S.U., S.S.), National University of Singapore, Singapore 117456;NUS Environmental Research Institute, National University of Singapore, Singapore 117411 (S.U., M.R., L.B.K., S.S.); andSingapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, Singapore 637551 (S.S.).
authors.forename: Shivshankar
authors.identifier: 0000-0001-7478-1194
authors.initials: S
authors.lastname: Umashankar
authors.affiliation: Metabolites Biology Lab, Department of Biological Sciences, National University of Singapore, Singapore 117543 (A.R., S.U., M.R., L.B.K., J.A.S.B., S.S.);Synthetic Biology Research Consortium (A.R., S.S.) and Singapore Centre for Environmental Life Science Engineering (S.U., S.S.), National University of Singapore, Singapore 117456;NUS Environmental Research Institute, National University of Singapore, Singapore 117411 (S.U., M.R., L.B.K., S.S.); andSingapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, Singapore 637551 (S.S.).
authors.forename: Megha
authors.identifier: 0000-0002-0613-5227
authors.initials: M
authors.lastname: Rai
authors.affiliation: Metabolites Biology Lab, Department of Biological Sciences, National University of Singapore, Singapore 117543 (A.R., S.U., M.R., L.B.K., J.A.S.B., S.S.);Synthetic Biology Research Consortium (A.R., S.S.) and Singapore Centre for Environmental Life Science Engineering (S.U., S.S.), National University of Singapore, Singapore 117456;NUS Environmental Research Institute, National University of Singapore, Singapore 117411 (S.U., M.R., L.B.K., S.S.); andSingapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, Singapore 637551 (S.S.).
authors.forename: Lim Boon
authors.initials: LB
authors.lastname: Kiat
authors.affiliation: Metabolites Biology Lab, Department of Biological Sciences, National University of Singapore, Singapore 117543 (A.R., S.U., M.R., L.B.K., J.A.S.B., S.S.);Synthetic Biology Research Consortium (A.R., S.S.) and Singapore Centre for Environmental Life Science Engineering (S.U., S.S.), National University of Singapore, Singapore 117456;NUS Environmental Research Institute, National University of Singapore, Singapore 117411 (S.U., M.R., L.B.K., S.S.); andSingapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, Singapore 637551 (S.S.).
authors.forename: Johanan Aow Shao
authors.identifier: 0000-0002-1438-8769
authors.initials: JA
authors.lastname: Bing
authors.affiliation: Metabolites Biology Lab, Department of Biological Sciences, National University of Singapore, Singapore 117543 (A.R., S.U., M.R., L.B.K., J.A.S.B., S.S.);Synthetic Biology Research Consortium (A.R., S.S.) and Singapore Centre for Environmental Life Science Engineering (S.U., S.S.), National University of Singapore, Singapore 117456;NUS Environmental Research Institute, National University of Singapore, Singapore 117411 (S.U., M.R., L.B.K., S.S.); andSingapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, Singapore 637551 (S.S.) sanjay@nus.edu.sg.
authors.forename: Sanjay
authors.identifier: 0000-0001-6391-0624
authors.initials: S
authors.lastname: Swarup
mesh_terms: D017360:Arabidopsis / Q000235:genetics / Q000378:metabolism*; D029681:Arabidopsis Proteins / Q000235:genetics / Q000378:metabolism*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D053898:Biosynthetic Pathways; D005419:Flavonoids / Q000378:metabolism; D018506:Gene Expression Regulation, Plant; D006031:Glycosylation; D010937:Plant Growth Regulators / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D013312:Stress, Physiological; D059467:Transcriptome
chemical_list: D029681:Arabidopsis Proteins; D051792:Basic Helix-Loop-Helix Proteins; D005419:Flavonoids; D010937:Plant Growth Regulators; C417767:TT8 protein, Arabidopsis