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
A widespread group of phenolics in plants termed coumarins constitute lactones of phenylpropanoids with a 2H-benzopyran-2-one nucleus [Brown86a] [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].
Brown86a: 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.
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
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
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
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
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
©2014 SRI International, 333 Ravenswood Avenue, Menlo Park, CA 94025-3493