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MetaCyc Pathway: scopoletin biosynthesis

Enzyme View:

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 Phenylpropanoid Derivatives Biosynthesis Coumarins Biosynthesis

Some taxa known to possess this pathway include ? : Arabidopsis thaliana col , Ruta graveolens

Expected Taxonomic Range: Viridiplantae

Summary:
Scopoletin (7-hydroxy-6-methoxy coumarin) is a hydroxycoumarin. It is found in a number of plant species including Arabidopsis, cassava, sweet potato, sunflower, cotton and tobacco [Bayoumi08, Kai08]. Scopoletin is thought to be involved in plant defense responses. In tobacco, accumulation of scopoletin was shown to strongly correlate with tobacco mosaic virus-induced localized acquired resistance [Costet02]. Scopoletin was indicated to have many pharmacological effects as well, such as antidepressant [Capra10], anti-arthritic [Pan], anti-gastro-esophageal inflammatory [Mahattanadul11], potential in ameliorate insulin resistance [Zhang10c], and potential in treatment of hypertriglyceridemia [Yang07e]. In addition, it was also shown to have antitermite activity [Adfa10].

The biosynthesis pathway leading to scopoletin in plants is still largely unclear. Genetic and biochemical evidence in Arabidopsis supports that, in this plant, scopoletin is derived from feruloyl-CoA, not ferulate [Kai08] as previously thought. A 2-oxoglutarate-dependent dioxygenase is responsible for the ortho-hydroxylation of feruloyl-CoA, an important branch point from lignin biosynthesis. Ortho-hydroxylation of the feruloyl-CoA aromatic ring is followed by trans-cis isomerization of the side chain, and subsequent lactonization to close the ring and yield scopoletin. The mechanism of the E-Z isomerization step in the biosynthesis of coumarins varies between genera or even species, for being either light-dependent photoisomerization or light-independent enzyme catalyzed isomerization [Bayoumi08]. It is not clear what mechanism is involved in the above depicted scopoletin biosynthesis pathway in Arabidopsis.

In cassava, where scopoletin and its glycoside derivative appear to be involved in significant crop losses due to Post-harvest Physiological Deterioration (PPD), some detailed experiments performed with isotopic intermediates have shed light on the reactions comprising this biosynthetic pathway in Manihot esculenta [Bayoumi08].

Credits:
Created 19-Apr-2011 by Zhang P , TAIR


References

Adfa10: Adfa M, Yoshimura T, Komura K, Koketsu M (2010). "Antitermite activities of coumarin derivatives and scopoletin from Protium javanicum Burm. f." J Chem Ecol 36(7);720-6. PMID: 20563628

Bayoumi08: Bayoumi SA, Rowan MG, Blagbrough IS, Beeching JR (2008). "Biosynthesis of scopoletin and scopolin in cassava roots during post-harvest physiological deterioration: the E-Z-isomerisation stage." Phytochemistry 69(17);2928-36. PMID: 19004461

Capra10: Capra JC, Cunha MP, Machado DG, Zomkowski AD, Mendes BG, Santos AR, Pizzolatti MG, Rodrigues AL (2010). "Antidepressant-like effect of scopoletin, a coumarin isolated from Polygala sabulosa (Polygalaceae) in mice: evidence for the involvement of monoaminergic systems." Eur J Pharmacol 643(2-3);232-8. PMID: 20599906

Costet02: Costet L, Fritig B, Kauffmann S (2002). "Scopoletin expression in elicitor-treated and tobacco mosaic virus-infected tobacco plants." Physiol Plant 115(2);228-235. PMID: 12060240

Kai08: Kai K, Mizutani M, Kawamura N, Yamamoto R, Tamai M, Yamaguchi H, Sakata K, Shimizu B (2008). "Scopoletin is biosynthesized via ortho-hydroxylation of feruloyl CoA by a 2-oxoglutarate-dependent dioxygenase in Arabidopsis thaliana." Plant J 55(6);989-99. PMID: 18547395

Mahattanadul11: Mahattanadul S, Ridtitid W, Nima S, Phdoongsombut N, Ratanasuwon P, Kasiwong S (2011). "Effects of Morinda citrifolia aqueous fruit extract and its biomarker scopoletin on reflux esophagitis and gastric ulcer in rats." J Ethnopharmacol 134(2);243-50. PMID: 21163341

Pan: Pan R, Dai Y, Gao XH, Lu D, Xia YF "Inhibition of vascular endothelial growth factor-induced angiogenesis by scopoletin through interrupting the autophosphorylation of VEGF receptor 2 and its downstream signaling pathways." Vascul Pharmacol 54(1-2);18-28. PMID: 21078410

Yang07e: Yang JY, Koo JH, Yoon HY, Lee JH, Park BH, Kim JS, Chi MS, Park JW (2007). "Effect of scopoletin on lipoprotein lipase activity in 3T3-L1 adipocytes." Int J Mol Med 20(4);527-31. PMID: 17786283

Zhang10c: Zhang WY, Lee JJ, Kim Y, Kim IS, Park JS, Myung CS (2010). "Amelioration of insulin resistance by scopoletin in high-glucose-induced, insulin-resistant HepG2 cells." Horm Metab Res 42(13);930-5. PMID: 20886413

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

Bayoumi08a: Bayoumi SA, Rowan MG, Beeching JR, Blagbrough IS (2008). "Investigation of biosynthetic pathways to hydroxycoumarins during post-harvest physiological deterioration in Cassava roots by using stable isotope labelling." Chembiochem 9(18);3013-22. PMID: 19035613

Curry99: Curry, J, Aluru, M, Mendoza, M, Nevarez, J, Melendrez, M, O' Connell, M. A (1999). "Transcripts for posssible capsaicinoid biosynthetic genes are differentially accumulated in pungent and non-pungent Capsicum." Plant Science, 148, 47-57.

Grienenberger09: Grienenberger E, Besseau S, Geoffroy P, Debayle D, Heintz D, Lapierre C, Pollet B, Heitz T, Legrand M (2009). "A BAHD acyltransferase is expressed in the tapetum of Arabidopsis anthers and is involved in the synthesis of hydroxycinnamoyl spermidines." Plant J 58(2);246-59. PMID: 19077165

Ibdah03: Ibdah M, Zhang XH, Schmidt J, Vogt T (2003). "A novel Mg(2+)-dependent O-methyltransferase in the phenylpropanoid metabolism of Mesembryanthemum crystallinum." J Biol Chem 278(45);43961-72. PMID: 12941960

Kopycki08: Kopycki JG, Rauh D, Chumanevich AA, Neumann P, Vogt T, Stubbs MT (2008). "Biochemical and structural analysis of substrate promiscuity in plant Mg2+-dependent O-methyltransferases." J Mol Biol 378(1);154-64. PMID: 18342334

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

Lepelley07: Lepelley, M, Simkina, A, Cheminadea, G, Cailleta, V, Tremillon, N, McCarthy, J (2007). "Chlorogenic acid synthesis in coffee: An analysis of CGA content and real-time RT-PCR expression of HCT, HQT, C3H1, and CCoAOMT1 genes during grain development in C. canephora." Plant Science, 172, 978-996.

Lin13a: Lin Y, Sun X, Yuan Q, Yan Y (2013). "Combinatorial biosynthesis of plant-specific coumarins in bacteria." Metab Eng 18;69-77. PMID: 23644174

Matsumoto12: Matsumoto S, Mizutani M, Sakata K, Shimizu B (2012). "Molecular cloning and functional analysis of the ortho-hydroxylases of p-coumaroyl coenzyme A/feruloyl coenzyme A involved in formation of umbelliferone and scopoletin in sweet potato, Ipomoea batatas (L.) Lam." Phytochemistry 74;49-57. PMID: 22169019

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

Vialart11: Vialart G, Hehn A, Olry A, Ito K, Krieger C, Larbat R, Paris C, Shimizu BI, Sugimoto Y, Mizutani M, Bourgaud F (2011). "A 2-oxoglutarate-dependent dioxygenase from Ruta graveolens L. exhibits p-coumaroyl CoA 2'-hydroxylase activity (C2'H): a missing step in the synthesis of umbelliferone in plants." Plant J. PMID: 22168819

Wils13: Wils CR, Brandt W, Manke K, Vogt T (2013). "A single amino acid determines position specificity of an Arabidopsis thaliana CCoAOMT-like O-methyltransferase." FEBS Lett 587(6);683-9. PMID: 23416302


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 Sat Nov 22, 2014, BIOCYC14A.