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MetaCyc Pathway: coumarin biosynthesis (via 2-coumarate)

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 ? : Melilotus albus

Expected Taxonomic Range: Magnoliophyta

Summary:
General Background

A widespread group of phenolics in plants termed coumarins constitute lactones of phenylpropanoids with a 2H-benzopyran-2-one nucleus [Brown86] [Seigler98]. At least 1000 natural occurring coumarins, among them about 300 simple coumarins have been found in many families of higher plants [Berenbaum91] with an especially high number of structural variations encountered in the Apiaceae [Seigler98]. The biosynthesis of the simplest member described in this pathway, i.e. coumarin represents both the specific compound and serves as an eponym of the entire compound class.

Coumarin belongs to the most common coumarins in plants. The numerous pharmacological and physiological effects of coumarin and its more complex derivatives such as the furanocoumarins and prenylated coumarins have drawn significant interest of researchers across different scientific areas. Coumarins are known to exhibit anti-inflammatory as well as antioxidant activities and often serve as model compounds for synthetic drugs [Fylaktakidou04] [Curini06]. Moreover, extensive research into their pharmacological and therapeutic properties for many years has resulted in the acknowledgment of their therapeutic role in the treatment of cancer [Lacy04].

About This Pathway

In contrast to most of the coumarins, which are biosynthesized through 4-coumaric acid and umbelliferone, the formation of coumarin occurs via 2-coumaric acid [Gestetner74]. In general phenylalanine and trans-cinnamic acid are considered the precursor for the coumarin biosynthesis but Stoker [Stoker62] also reported the formation of coumarin from cis-cinnamic acid. Although free coumarin is found in small amounts in plants their β-glucoside(s) is the predominant accumulating compound. The corresponding glucosyltransferase has been partially purified from and characterized in Melilotus albus [Kleinhofs67] [Poulton80]. Interestingly, the formed trans-2-coumarate β-D-glucoside was not accepted as substrate for the subsequent β-glucosidase reaction. The enzyme only catalyzed the cis-isomer, i.e. coumarinic acid β-D-glucoside (also referred to as bound coumarin - [Kosuge61a]) forming coumarinate [Kosuge61].

The way the isomerization occurs is not entirely resolved. While there is strong evidence that the trans-cis isomerization occurs spontaneously by means of UV-light [Kleinhofs66] [Haskins64] the existence of a light-induced isomerase enzyme system has not been ruled out. Stoker [Stoker64] presented evidence for the involvement of an isomerase system in this process and found that plants kept in daylight or in the dark did not significantly differ with regard to the amount of coumarin. The last step of the pathway is the spontaneous lactonization of coumarinate forming coumarin.

The typical 'hay' smell of coumarin is only found when plants are injured. It has been established that the glucosylated coumarins accumulate in the vacuole while the β-glucosidase is located to the extraplasmatic space [Oba81]. Hence, the physical contact of the enzyme and its substrate (coumarin glucosides) only occurs after the breakup of the cell and its organelles. Coumarin itself is not a dead end product but is rather readily further metabolized [Kosuge59].

Credits:
Created 11-May-2006 by Foerster H , TAIR


References

Berenbaum91: Berenbaum MR (1991). "Coumarins." In: Herbivores:Their interactions with secondary metabolites. Vol 1, Rosenthal GA, Berenbaum MR (eds.), Academic Press, San Diego, 221-249.

Brown86: Brown SA (1986). "Biochemistry of plant coumarins." In: Recent advances in phytochemistry, Volume 20: The shikimic acid pathway. Conn EE (ed.), Plenum Press New York and London, 1986, 287-316.

Curini06: Curini M, Cravotto G, Epifano F, Giannone G (2006). "Chemistry and biological activity of natural and synthetic prenyloxycoumarins." Curr Med Chem 13(2);199-222. PMID: 16472213

Fylaktakidou04: Fylaktakidou KC, Hadjipavlou-Litina DJ, Litinas KE, Nicolaides DN (2004). "Natural and synthetic coumarin derivatives with anti-inflammatory/ antioxidant activities." Curr Pharm Des 10(30);3813-33. PMID: 15579073

Gestetner74: Gestetner B, Conn EE (1974). "The 2-hydroxylation of trans-cinnamic acid by chloroplasts from Melilotus alba Desr." Arch Biochem Biophys 163(2);617-24. PMID: 4153528

Haskins64: Haskins FA, Williams LG, Gorz HJ (1964). "Light-Induced Trans to Cis Conversion of beta-d-Glucosyl o-Hydroxycinnamic Acid in Melilotus alba Leaves." Plant Physiol 39(5);777-781. PMID: 16656000

Kleinhofs66: Kleinhofs A, Haskins FA, Gorz HJ (1966). "Ultraviolet-induced isomerization of beta-D-glucosyl omicron-hydroxycinnamic acid on filter paper." J Chromatogr 22(1);184-6. PMID: 5921806

Kleinhofs67: Kleinhofs A, Haskins A, Gorz HJ (1967). "Trans-O-hydroxycinnamic acid glucosylation in cell-free extracts of Melilotus alba." Phytochemistry, 6, 1313-1318.

Kosuge59: Kosuge T, Conn EE (1959). "The metabolism of aromatic compounds in higher plants. I. Coumarin and o-coumaric acid." J Biol Chem 234(8);2133-7. PMID: 13673026

Kosuge61: Kosuge T, Conn EE (1961). "The metabolism of aromatic compounds in higher plants. III. The beta-glucosides of o-coumaric, coumarinic, and melilotic acids." J Biol Chem 236;1617-21. PMID: 13753452

Kosuge61a: Kosuge T (1961). "Studies on the identity of bound coumarin in sweet clover." Arch Biochem Biophys 95;211-8. PMID: 14458750

Lacy04: Lacy A, O'Kennedy R (2004). "Studies on coumarins and coumarin-related compounds to determine their therapeutic role in the treatment of cancer." Curr Pharm Des 10(30);3797-811. PMID: 15579072

Oba81: Oba K, Conn EE, Canut H, Boudet AM (1981). "Subcellular Localization of 2-(beta-d-Glucosyloxy)-Cinnamic Acids and the Related beta-glucosidase in Leaves of Melilotus alba Desr." Plant Physiol 68(6);1359-1363. PMID: 16662108

Poulton80: Poulton JE, McRee DE, Conn EE (1980). "Intracellular Localization of Two Enzymes Involved in Coumarin Biosynthesis in Melilotus alba." Plant Physiol 65(2);171-175. PMID: 16661155

Seigler98: Seigler DS (1998). "Plant secondary metabolism." Kluwer Academic Publishers, Boston Dordrecht London.

Stoker62: Stoker JR, Bellis DM (1962). "The biosynthesis of coumarin in Melilotus alba." J Biol Chem 237;2303-5. PMID: 13917373

Stoker64: Stoker JR (1964). "The biosynthesis of coumarin in Melilotus alba." Biochem Biophys Res Commun 14;17-20. PMID: 5836500

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

FraissinetTache98: Fraissinet-Tachet L, Baltz R, Chong J, Kauffmann S, Fritig B, Saindrenan P (1998). "Two tobacco genes induced by infection, elicitor and salicylic acid encode glucosyltransferases acting on phenylpropanoids and benzoic acid derivatives, including salicylic acid." FEBS Lett 437(3);319-23. PMID: 9824316

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

Lazarowski03: Lazarowski ER, Shea DA, Boucher RC, Harden TK (2003). "Release of cellular UDP-glucose as a potential extracellular signaling molecule." Mol Pharmacol 63(5);1190-7. PMID: 12695547


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 Mon Nov 24, 2014, biocyc13.