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MetaCyc Pathway: tetrahydroxyxanthone biosynthesis (from 3-hydroxybenzoate)

This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Superclasses: Biosynthesis Secondary Metabolites Biosynthesis Xanthones Biosynthesis

Some taxa known to possess this pathway include ? : Centaurium erythraea

Expected Taxonomic Range: Tracheophyta

Summary:
General Background

Xanthones are yellow pigments of phenolic origin restricted in occurrence to only a few families of higher plants and some fungi and lichens. The majority of xanthones is rarely glucosylated and has been found in basically two families of higher plants, the Clusiaceae (syn. Guttiferae) and Gentianaceae [Hostettmann89] [Bennett89]. However, xanthones also appear sporadically throughout the remainder of the plant kingdom. Xanthone-C-glucosides such as mangiferin are the exception with a much wider distribution among plants and also arising in ferns and fungi [Hostettmann89].

Xanthones can be classified based on their oxygenation, prenylation and glucosylation pattern. The majority of xanthones isolated so far are of the tetraoxygenated-type which have been intensively studied in plants of the Guttiferae and Gentianaceae but are reported from 12 other plant families as well [Peres00]. The restricted biosynthesis of xanthones and their plant-specific substitution pattern has been employed as a useful marker for systematic purposes, i.e. comparing the phyletic order of genera within the Guttiferae [Da73] and chemotaxonomic differentiation between plant families [Sultanbawa80].

Xanthones posses a number of remarkable pharmacological traits and bioactivities (summarized in [Peres00]) and have been used as, e.g. cardiovascular protective agents [Jiang04] and antitumor promotors [Ito98]. Tetrahydroxylated xanthones can be induced by phytopathogens [Jankovic02] and accumulate in calli and cell suspension upon treatment with plant hormones and supplements, such as naphtaleneacetic acid (NAA) in combination with kinetin [Dias00].

About This Pathway

The biosynthesis of plant xanthones originates mainly from a mixed shikimate-acetate pathway, however xanthones entirely derived from acetate have also been reported in lower plants [Peres00] [Hostettmann89]. The main steps in the xanthone biosynthesis involve the condensation of shikimate and acetate moieties which constitute a benzophenone intermediate followed by a regioselective, oxidative mediated intra-molecular coupling to form the xanthone ring [Peters98].

The shikimate derivatives used as entry compounds for the tetrahydroxyxanthone biosynthesis differ in relation to the investigated plants (Hypericum androsaemum vs Centaurium erythraea) [Abd01] [Abd02]. These plants belong to different families that seem to have developed biosynthetic variants of the tetrahydroxyxanthone synthesis which involves enzymes of diverse regioselectivity and substrate preference and leads to varying intermediates [Peters98] [Schmidt97].

The biosynthesis of tetrahydroxyxanthone via 3-hydroxybenzoate (this pathway) in Centaurium erythraea is obtained by the stepwise condensation of 3 malonyl-CoA and 3-hydroxybenzoyl-CoA to form an intermediate tetrahydroxybenzophenone. The crucial step in this biosynthesis is the cyclization of the benzophenone to form a xanthone, catalyzed by xanthon synthases. In Centaurium erythraea the xanthone synthase converts the tetrahydroxybenzophenone intermediate regioselective to 1,3,5-trihydroxyxanthone. Therefore all xanthones and their derivatives in Centaurium erythraea are 5-oxygenated in contrast to the constituents in the Hypericum androsaemum pathway (tetrahydroxyxanthone biosynthesis (from benzoate)) which all carry a 7-hydroxy group [Peters98].

The last step in the biosynthesis of the tetrahydroxyxanthones is the introduction of a hydroxyl group to the C-ring of the xanthone skeleton. This reaction is carried out by the plant-specific Cytochrome P450-dependend monooxygenase, xanthone-6-hydroxylase, to form 1,3,5,6-tetrahydroxyxanthone [Schmidt00]. Cell cultures of Centaurium erythraea furthermore accumulate 3,5,6,7,8-pentamethoxy-1-O-primeverosyl-xanthone [Beerhues94] as the main xanthone which implies two additional hydroxylation steps of the corresponding tetrahydroxyxanthone not yet described in the literature.

Another representative of the Gentianaceae, chirayta (Swertia chirata), again hydroxylates 1,3,5-trihydroxyxanthone in the 8-position of the C-ring resulting in the major xanthone of this species 1,3,5,8-tetrahydroxyxanthone [Wang03f]. However, the enzyme and corresponding reaction involved remains to be characterized.

Superpathways: superpathway of tetrahydroxyxanthone biosynthesis

Credits:
Created 29-Sep-2005 by Foerster H , TAIR


References

Abd01: Abd El-Mawla AM, Schmidt W, Beerhues L (2001). "Cinnamic acid is a precursor of benzoic acids in cell cultures of Hypericum androsaemum L. but not in cell cultures of Centaurium erythraea RAFN." Planta 212(2);288-93. PMID: 11216850

Abd02: Abd El-Mawla AM, Beerhues L (2002). "Benzoic acid biosynthesis in cell cultures of Hypericum androsaemum." Planta 214(5);727-33. PMID: 11882941

Beerhues94: Beerhues L, Berger U (1994). "Xanthones in cell suspension cultures of two Centaurium species." Phytochemistry, 35(5), 1227-1231.

Bennett89: Bennett GJ, Lee H-H (1989). "Xanthones from Guttiferae." Phytochemistry, 28(4), 967-998.

Da73: Da Mata Rezende CMA, Gottlieb OR (1973). "Xanthones as Systematic Markers." Biochemical Systematics., 1, 111 - 118.

Dias00: Dias ACP, Seabra RM, Andrade PB, Ferreres F, Fernandes-Ferreira M (2000). "Xanthone biosynthesis and accumulation in calli and suspended cells of Hypericum androsaemum." Plant Science, 150, 93-101.

Hostettmann89: Hostettmann K, Hostettmann M (1989). "Xanthones." In: Dey, PM., Harborne JB (eds) Methods in Plant biochemistry, Harborne JB (editor) Vol 1, Plant Phenolics; Academic Press, London, San Diego, New York, Berkeley, Boston, Sydney, Tokyo, Toronto, 493-508.

Ito98: Ito C, Itoigawa M, Furukawa H, Rao KS, Enjo F, Bu P, Takayasu J, Tokuda H, Nishino H (1998). "Xanthones as inhibitors of Epstein-Barr virus activation." Cancer Lett 132(1-2);113-7. PMID: 10397461

Jankovic02: Jankovic T, Krstic D, Savikin-Fodulovic K, Menkovic N, Grubisic D (2002). "Xanthones and secoiridoids from hairy root cultures of Centaurium erythraea and C. pulchellum." Planta Med 68(10);944-6. PMID: 12391565

Jiang04: Jiang DJ, Dai Z, Li YJ (2004). "Pharmacological effects of xanthones as cardiovascular protective agents." Cardiovasc Drug Rev 22(2);91-102. PMID: 15179447

Peres00: Peres V, Nagem TJ, de Oliveira FF (2000). "Tetraoxygenated naturally occurring xanthones." Phytochemistry 55(7);683-710. PMID: 11190384

Peters98: Peters S, Schmidt W, Beerhues L (1998). "Regioselective oxidative phenol couplings of 2,3',4,6-tetrahydroxybenzophenone in cell cultures of Centaurium erythraea RAFN and Hypericum androsaemum L." Planta, 204: 64-69.

Schmidt00: Schmidt W, Peters S, Beerhues L (2000). "Xanthone 6-hydroxylase from cell cultures of Centaurium erythraea RAFN and Hypericum androsaemium L." Phytochemistry 53(4);427-31. PMID: 10731018

Schmidt97: Schmidt W, Beerhues L (1997). "Alternative pathways of xanthone biosynthesis in cell cultures of Hypericum androsaemum L." FEBS Lett 420(2-3);143-6. PMID: 9459298

Sultanbawa80: Sultanbawa MUS (1980). "Xanthonoids of tropical plants." Tetrahedron, 36, 1465 - 1506.

Wang03f: Wang CZ, Maier UH, Keil M, Zenk MH, Bacher A, Rohdich F, Eisenreich W (2003). "Phenylalanine-independent biosynthesis of 1,3,5,8-tetrahydroxyxanthone. A retrobiosynthetic NMR study with root cultures of Swertia chirata." Eur J Biochem 270(14);2950-8. PMID: 12846828

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Barillas00: Barillas W, Beerhues L (2000). "3-Hydroxybenzoate:coenzyme A ligase from cell cultures of Centaurium erythraea: isolation and characterization." Biol Chem 381(2);155-60. PMID: 10746747

Barillas97: Barillas W, Beerhues L (1997). "3-Hydroxybenzoate:coenzyme A ligase and 4-coumarate:coenzyme A ligase from cultured cells of Centaurium erythraea." Planta 202(1);112-6. PMID: 9177055

Beerhues96: Beerhues L (1996). "Benzophenone synthase from cultured cells of Centaurium erythraea." FEBS Lett 383(3);264-6. PMID: 8925910

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

Rubio06: Rubio S, Larson TR, Gonzalez-Guzman M, Alejandro S, Graham IA, Serrano R, Rodriguez PL (2006). "An Arabidopsis mutant impaired in coenzyme A biosynthesis is sugar dependent for seedling establishment." Plant Physiol 140(3);830-43. PMID: 16415216


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Thu Dec 18, 2014, biocyc13.