The Peroxidative Cleavage of Kaempferol Contributes to the Biosynthesis of the Benzenoid Moiety of Ubiquinone in Plants

Abstract

Land plants possess the unique capacity to derive the benzenoid moiety of the vital respiratory cofactor, ubiquinone (coenzyme Q), from phenylpropanoid metabolism via b-oxidation of p-coumarate to form 4-hydroxybenzoate. Approximately half of the ubiquinone in plants comes from this pathway; the origin of the rest remains enigmatic. In this study, Phe-[Ring-13 C 6 ] feeding assays and gene network reconstructions uncovered a connection between the biosynthesis of ubiquinone and that of flavonoids in Arabidopsis (Arabidopsis thaliana). Quantification of ubiquinone in Arabidopsis and tomato (Solanum lycopersicum) mutants in flavonoid biosynthesis pinpointed the corresponding metabolic branch-point as lying between flavanone-3-hydroxylase and flavonoid-39-hydroxylase. Further isotopic labeling and chemical rescue experiments demonstrated that the B-ring of kaempferol is incorporated into ubiquinone. Moreover, heme-dependent peroxidase activities were shown to be responsible for the cleavage of B-ring of kaempferol to form 4-hydroxybenzoate. By contrast, kaempferol 3-b-D-glucopyranoside, dihydrokaempferol, and naringenin were refractory to peroxidative cleavage. Collectively, these data indicate that kaempferol contributes to the biosynthesis of a vital respiratory cofactor, resulting in an extraordinary metabolic arrangement where a specialized metabolite serves as a precursor for a primary metabolite. Evidence is also provided that the ubiquinone content of tomato fruits can be manipulated via deregulation of flavonoid biosynthesis.

General and specialized tyrosine metabolism pathways in plants

“…The 1,4-benzoquinone ring precursor for ubiquinone 4-HB is derived from tyrosine and phenylalanine in plants (Block et al 2014). Significant progresses have been made recently in characterization of the biosynthesis of 4-HB from phenylalanine (Block et al 2014;Soubeyrand et al 2018); by contrast, much less is known about the generation of 4-HB from tyrosine. In S. cerevisiae, the first and last reactions of this pathway, namely the deamination of tyrosine to pHPP and the oxidation of 4-hydroxybenzaldehyde to 4-HB, have been characterized recently (Payet et al 2016;Stefely et al 2016); however, the evidence that TAT is involved in 4-HB formation is still lacking in plants.…”

“…In S. cerevisiae, the first and last reactions of this pathway, namely the deamination of tyrosine to pHPP and the oxidation of 4-hydroxybenzaldehyde to 4-HB, have been characterized recently (Payet et al 2016;Stefely et al 2016); however, the evidence that TAT is involved in 4-HB formation is still lacking in plants. The endogenous levels of 4-HB may limit the ubiquinone production, since elevation in its pool has reported to have a positive effect on ubiquinone biosynthesis in Arabidopsis and tomato (Block et al 2014;Soubeyrand et al 2018). Further investigation of the tyrosine-derived metabolites and their connection to the phenylpropanoid pathway would provide new insights into the ubiquinone biosynthesis and help to improve nutritional value of crop products.…”

Metabolism of the Flavonol Kaempferol in Kidney Cells Liberates the B-ring to Enter Coenzyme Q Biosynthesis

“…Two hypotheses were proposed: (1) Kaempferol could be a direct substrate of COQ2 in the CoQ biosynthetic pathway and would be subsequently metabolized by the different COQ proteins until it reached the final structure of CoQ; or alternatively, (2) kaempferol could be metabolized in the cell to produce a potential CoQ ring precursor, which would be then integrated in the CoQ biosynthetic pathway [17]. In a recent study, Soubeyrand and co-authors [18] described that, in plants, the biosynthetic pathways of flavonoids and CoQ are indeed connected and that kaempferol can serve as a precursor for the synthesis of CoQ. They proved that the B-ring of kaempferol is subjected to peroxidative cleavage, to give 4-hydroxybenzoic acid (4HB), a common precursor of the benzoquinone ring of CoQ [18].…”

“…In a recent study, Soubeyrand and co-authors [18] described that, in plants, the biosynthetic pathways of flavonoids and CoQ are indeed connected and that kaempferol can serve as a precursor for the synthesis of CoQ. They proved that the B-ring of kaempferol is subjected to peroxidative cleavage, to give 4-hydroxybenzoic acid (4HB), a common precursor of the benzoquinone ring of CoQ [18].…”

Questions about Coenzyme Q? A New Genetic/Metabolic Study Has Answers

“…However, the pathway and responsible enzymes had long remained unclear. Now, Soubeyrand et al (2018) bring some serious genetic and metabolic analyses to bear on this question. The authors first used metabolic labeling experiments, feeding Phe-[Ring-13 C 6 ] to various Arabidopsis (Arabidopsis thaliana) mutants that are affected in different steps of the biosynthesis of the precursor 4-hydroxybenzoate.…”