title: Feedback inhibition of the general phenylpropanoid and flavonol biosynthetic pathways upon a compromised flavonol-3-O-glycosylation.
abstract: Flavonols, phenylalanine-derived secondary metabolites, have protective and regulatory functions in plants. In Arabidopsis thaliana, they are consecutively glycosylated at their 3-OH and 7-OH groups. UGT78D1 and UGT78D2 are the major flavonol 3-O-glycosyltransferases in Arabidopsis leaves. The ugt78d1 ugt78d2 double mutant, which was strongly compromised in the initial 3-O-glycosylation, showed a severe and specific repression of flavonol biosynthesis, retaining only one-third of the wild-type level. This metabolic phenotype was associated with a repressed transcription of several flavonol biosynthetic genes including the committed step chalcone synthase [(CHS) or TRANSPARENT TESTA 4 (TT4)]. Furthermore, the committed step of the upstream, general phenylpropanoid pathway, phenylalanine ammonia-lyase (PAL), was down-regulated in its enzyme activity and in the transcription of the flavonol-related PAL1 and PAL2. However, a complete blocking of flavonoid biosynthesis at CHS released PAL inhibition in a tt4 ugt78d1 ugt78d2 line. PAL activity was even enhanced in the flavonol synthase 1 mutant, which compromises the final formation of flavonol aglycones. The dependence of the PAL feedback inhibition on flavonols was confirmed by chemical complementation of tt4 ugt78d1 ugt78d2 using naringenin, a downstream flavonoid intermediate, which restored the PAL repression. Although aglycones were not analytically detectable, this study provides genetic evidence for a novel, flavonol-dependent feedback inhibition of the flavonol biosynthetic pathway and PAL. It was conditioned by the compromised flavonol-3-O-conjugation and a decrease in flavonol content, yet dependent on a residual, flavonol synthase 1 (FLS1)-related capacity to form flavonol aglycones. Thus, this regulation would not react to a reduced metabolic flux into flavonol biosynthesis, but it might prevent the accumulation of non-glycosylated, toxic flavonols.
authors.affiliation: Institute of Biochemical Plant Pathology, Helmholtz Zentrum München, German Research Center for Environmental Health, D-85764 Neuherberg, Germany.
authors.forename: Ruohe
authors.initials: R
authors.lastname: Yin
authors.forename: Burkhard
authors.initials: B
authors.lastname: Messner
authors.forename: Theresa
authors.initials: T
authors.lastname: Faus-Kessler
authors.forename: Thomas
authors.initials: T
authors.lastname: Hoffmann
authors.forename: Wilfried
authors.initials: W
authors.lastname: Schwab
authors.forename: Mohammad-Reza
authors.initials: MR
authors.lastname: Hajirezaei
authors.forename: Veronica
authors.initials: V
authors.lastname: von Saint Paul
authors.forename: Werner
authors.initials: W
authors.lastname: Heller
authors.forename: Anton R
authors.initials: AR
authors.lastname: Schäffner
mesh_terms: D017360:Arabidopsis / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D053898:Biosynthetic Pathways; D015536:Down-Regulation; D025461:Feedback, Physiological; D044948:Flavonols / Q000096:biosynthesis*; D018506:Gene Expression Regulation, Plant; D006031:Glycosylation; D016695:Glycosyltransferases / Q000235:genetics / Q000378:metabolism
chemical_list: D044948:Flavonols; D016695:Glycosyltransferases; C480037:UGT78D1 protein, Arabidopsis