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Curcumin Synthesis in Curcuma longa: Two Cooperating Enzymes

16/03/11 12:23 PM

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Curcumin Biosynthesis in Curcuma longa
Key references Katsuyama, Y., Kita, T., Funa, N., Horinouchi, S., 2009a. Curcuminoid biosynthesis by two type III polyketide synthases in the herb Curcuma longa. Journal of Biological Chemistry 284, 11160-11170. And quite new: Katsuyma,Y., Kita, T., Horinouchi, S., 2009b. Identification and characterization of multiple curcumin synthases from the herb Curcuma longa. FEBS Letters, 583, 2799-2783. In the context of this work you should also look at the 'Curcuminoid synthase' from rice, and on the application of the two-component system to phenylphenalenone biosynthesis: more...

Introduction
Curcuminoids are apparently exclusively found in the rhizomes of Curcuma longa (more...), and the predominant compound is curcumin (Fig. 1). Powdered turmeric rhizome is widely used a food additive and in Asian medicine; it is believed to have many beneficial effects on all sorts of ailments, see for recent discussions: Corson and Crews, 2007; Aggarwal et al., 2007, Anand et al., 2008; Srivastava and Mehta, 2009. Fig. 1. Major curcuminoids in Curcuma longa. Typical distributions in powdered turmeric are: Curcumin 2%, Demethoxycurcumin 0,7%, Bisdemethoxycurcumin 0,6% (Hiserodt et al., 1996).

Precursor-feeding studies suggested very early that the backbone consists of two phenylpropanoids (ferulate in the case of curcumin) which are connected by an acetate derived carbon unit. The same basic setup is found in many other substances, e.g. the phenylphenalenones (like anigorufone), and in the gingerols (one phenylpropanoid + a short chain fatty acid), and proposals for the biosynthetic reactions were discussed intensively (see for example the review in: Cooke and Edwards, 1980). The early precursor feeding studies for curcumin were apparently not conclusive; they could not clearly distinguish between two possibilities: a) starter phenylpropanoid-CoA, five extensions with malonyl-CoA, then ring-closure and further modifications, and b) biosynthesis from two phenylpropanoid-CoA and one malonyl-CoA (Roughly and Whiting, 1971; 1973). Much later (Schröder, 1997) I proposed that the biosynthesis of all of these natural products might start with a type III PKS reaction corresponding to the single condensation carried out by benzalacetone synthase, and that the resulting diketide is the basis for the synthesis of the final structures. At that time I was not aware of the finding that the biosynthesis was not that clear in the case of curcumin. Actually it was only recently that curcumin biosynthesis could be demonstrated in vitro in crude extracts of Curcuma longa. The activity was not purified, and thus it remained open whether one or several enzymes were involved (Ramirez-Ahumada et al., 2006).

Interesting new findings
It was quite important to see in a recent publication that curcumin biosynthesis could now be elucidated with enzymes from Curcuma longa (Katsuyama et al., 2009a), i.e. the plant that actually does synthesize curcuminoids. The findings are described here in a brief summary. The biosynthesis requires two cooperating enzymes; both are type III PKS, they share 62% identity. One of them corresponds to a previous entry in an EST-library, the other was obtained with degenerate primers/PCR. Both were expressed as recombinant proteins in E. coli. Figure 2 summarizes the reactions. Fig. 2. Model for the biosynthesis of curcumin. For comparison, have a look at the Curcuminoid synthase from rice.

http://www.biologie.uni-freiburg.de/data/bio2/schroeder/Curcumin_Biosynthesis.html

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i.. However. but two more sequences: AY739910 (= Wdf2) and AY973271 (= Wdf3). CURS. CURS2 and CURS3 (the first CURS was renamed to CURS1). but also the starter substrate for the next condensation in all type III PKS reactions carrying out more than one condensation. if the products were analyzed with the standard procedures. Incubations of CURS with starter substrates and the cinnamoyl-diketide-NAC in fact led to curcuminoid formation. 2006).or NAC-activated molecule). like gingerol (Ginger). Of course. they might compete for the same substrate. 4-Coumaroyl-CoA led at least to a detectable low production of benzalacetone. No activity at all was found with cinnamoyl-CoA. It therefore makes sense that feruloyl-CoA is an allosteric regulator of DCS: there would be no point in its using up all the feruloyl-CoA that is needed for the subsequent CURS reaction in a metabolic flow situation.. that it released the diketide CoA-ester rather than a diketide acid (which is likely to be decarboxylated non-enzymatically to the ketone). That is quite interesting in several points: It shows that C. most importantly. 4-coumaroyl-CoA... When the analysis was done directly with the incubation mixture: it turned out that the CoA-esters had been converted to the diketidyl-CoAs.5.. or feruloyl-CoA. not at the level of the curcuminoids. and. i.e. and a candidate enzyme for the first reaction ('DCS' function) has been described (more.html Page 2 of 5 . see the relationship tree. as suggested for the unusual enzyme from rice (more. but the values are much lower with WtPKS1 (about 55-60% identity).. suggesting that the modifications leading from 4-coumarate to ferulate residues was done on the phenylpropanoid level. each carrying out only one condensation. thyrsiflora a protein with the 'CURS' function had not been identified. i..0. indeed. longa uses two enzymes.biologie. Interestingly. DCS ( Diketide-CoA Synthase): That enzyme showed very little or no activity with cinnamoyl-CoA. the phenylphenalenones in Wachendorfia thyrsiflora. Both DCS and CURS use feruloyl-CoA as starter substrate. WtPKS1.. it could also be the diketide CoA: this is of course not only the product of the first condensation. but 4-coumaroyl-CoA and feruloyl-CoA gave trace amounts of curcuminoids. they revealed interesting differences in the substrate preferences. The results with DCS suggested that diketidyl-CoAs could be the 'real' substrates. Return to top A generalization of the 'two enzyme principle' ? There are other natural products that possibly share the same basic biosynthetic reactions. CURS (Curcumin Synthase): Incubations of that enzyme with cinnamoyl-CoA led to no products. The experiment revealed an efficient production of curcumin. but the databases actually do not only contain the characterized DCS candidate (AY727928. Return to top Update on new CURS-type enzymes A recent publication (Katsuyama et al..uni-freiburg.1.. The decisive point to detect the enzyme activity: do the analysis directly from the incubation. rather than a single enzyme using two different chain extenders. the statement that CURS synthesized a curcuminoid with a combination of feruloyl-CoA and the cinnamate diketide acid strongly suggests that the diketide is the chain extender: I am not aware of any type III PKS that can use a diketide acid as starter substrate (instead of an CoA. a point that could be important for the cooperation with the subsequent enzyme. However.. called Wdf1). suggesting that the enzyme carried out only one condensation.1.Curcumin Synthesis in Curcuma longa: Two Cooperating Enzymes 16/03/11 12:23 PM The enzymes 1. a very satisfying result. but the synthesis was the simplest feasible option). Taken together.. indicating that the enzyme in fact carried out only one condensation with malonyl-CoA. and therefore the authors synthesized a NAC (N-acetylcysteamine) derivative for cinnamoyl-diketide (certainly not the optimal choice. the kinetics of the enzyme with feruloyl-CoA suggested that the substrate was an allosteric regulator of the activity.. extraction with organic solvent and subsequent analysis. and most important in this context..e. These latter two are about 95% identical. The CURS reaction raises an interesting question: which is in this case the starter. The reaction was very efficient with feruloyl-CoA. the results indicate that curcumin in Curcumal longa is synthesized by the cooperation of two different type III PKS. which is the extender? That is not quite trivial because it is not necessarily 4-coumaroyl-CoA.01. longa can be generalized: In W. in assays simply containing feruloyl-CoA and malonyl-CoA. and this may indeed taken as suggestion that the composition of the curcuminoids in different cultivars may be influenced by the rate of expression of the different enzymes.e. do not use acidification or extraction with ethylacetate. If the findings with C. Nevertheless. the best substrate. 2009b) described the molecular and functional characterization of two more CURS-type enzymes.) that has no known physiological function..de/data/bio2/schroeder/Curcumin_Biosynthesis. Could this be candidates for a CURS function? This is proposed in the discussion http://www. Brand et al. 2. Both were closely related to each other and CURS1.. the most interesting experiment was the co-incubation of DCS and CURS.

In particular these latter negative results would not be expected for a CURS function.Raspberry (Rubus idaeus): more. One of the type III PKSs. Nevertheless.. (Note: this is different from benzalacetone !!) . Schierhorn. Chalcone synthase (CHS) related type III plant polyketide synthases (PKSs) are likely to be involved in the biosynthesis of diarylheptanoids (e. but no other products that are known to require CHSs or related enzymes (e.Curcuminoid synthase in rice: .. and CURS then converts the diketide-CoA esters into a curcuminoid scaffold. These results suggested that CURS2 synthesizes curcumin or demethoxycurcumin and CURS3 synthesizes curcumin..1. These results do not provide any clues for a role in phenylphenalenone biosynthesis. in particular since one would postulate an activity with aromatic CoA-esters. FEBS Letters 583... A. Return to top or to text Katsuyama. References Katsuyama. Y..... but the published PhD thesis of Silke Brand (Brand. In vitro analysis revealed that CURS2 preferred feruloyl-CoA as a starter substrate and CURS3 preferred both feruloyl-CoA and p-coumaroyl-CoA.. It was soluble and could easily be purified. but no such activity has been reported. Most importantly.. J. Despite much attention regarding the biosynthesis of curcuminoids because of their pharmaceutically important properties and biosynthetically intriguing structures. Funa. These findings thus revealed the curcumin biosynthetic route in turmeric. Kita.. Here we propose a pathway for curcuminoid biosynthesis in the herb C. Horinouchi. ..Curcuminoids: . Diketide Derivatives . PhD Thesis. There was activity with linear aliphatic CoA-esters (C3 to C8 CoA-esters).1. named diketide-CoA synthase (DCS). Co-incubation of DCS and CURS in the presence of feruloyl-CoA and malonyl-CoA yielded curcumin at high efficiency. and that WtPKS2 and WtPKS3 group with the curcumin synthase (CURS) from Curcuma longa: it is tempting to speculate that the 'two enzyme principle' discussed here might actually apply to the first reactions in phenylphenalenone biosynthesis. 2009b.. Taken together. A. Schröder. curcumin and polycyclic phenylphenalenones). or in assays containing the expected substrates and both Wdf1 and Wdf2.. N. bisdemethoxycurcumin and demethoxycurcumin..5. A homology-based RT-PCR strategy led to the identification of cDNAs for a type III PKS sharing only approximately 60% identity with typical CHSs.de/data/bio2/schroeder/Curcumin_Biosynthesis. Curcuminoids found in the rhizome of turmeric.html Page 3 of 5 . The results in brief (Brand.. WtPKS1 performed two condensation reactions and released pyrones..Benzylacetone: more. in German) does contain additional information that of course was not easily accessible to the Japanese group. The Brand et al... possess various biological activities.Rhubarb (Rheum palmatum): more. activity was also not detected in incubations with diketide-NAC derivatives. which includes two novel type III polyketide synthases (PKSs). Pflanzliche Polyketidsynthasen des Typ III in Wachendorfia thyrsiflora (Haemodoraceae). Two additional type III polyketide synthases. .Phenylphenalenones: more. 11160-11170.. although CURS itself possessed low activity for the synthesis of curcumin from feruloyl-CoA and malonyl-CoA. 2799-2783. Svatos.Curcuminoid biosynthesis by two cooperating enzymes in Curcuma longa: more.. Curcuma longa. Y. and the best results were obtained with 4-coumaroyl-CoA (80% of the products). (2006) paper does not provide information on the two other proteins. Friedrich-Schiller-Universität http://www.. including phenylpropionyl.biologie. 413-428. the expected release products. Curcuminoid biosynthesis by two type III polyketide synthases in the herb Curcuma longa. Return to text or go to a more detailed discussion Request a reprint Brand. B. catalyzed the in vitro formation of curcuminoids from cinnamoyl-diketide-N-acetylcysteamine (a mimic of the CoA ester) and feruloylCoA.g. The purified recombinant protein accepted a large variety of aromatic and aliphatic starter CoA esters. that are capable of curcuminoid synthesis were identified and characterized. It was named WtPKS1 (W. 2005): Wdf2: a recombinant protein was expressed in E.. T.. However. named CURS2 and CURS3. Planta 224.. no enzyme systems have been elucidated.. the activities could be tested. catalyzed the formation of feruloyl-diketide-CoA by condensing feruloyl-CoA and malonyl-CoA. S. thyrsiflora polyketide synthase 1).. We propose that WtPKS1 catalyses the first step in diarylheptanoid biosynthesis and that the observed pyrones are derailment products in the absence of downstream processing proteins. A type III polyketide synthase from Wachendorfia thyrsiflora and its role in diarylheptanoid and phenylphenalenone biosynthesis.and side-chain unsaturated phenylpropanoid-CoAs. 2005. Proposals .... Kita. Benzalacetones. 2009a.uni-freiburg. Root cultures from Wachendorfia thyrsiflora (Haemodoraceae) are a suitable source to search for such enzymes because they synthesize large amounts of phenylphenalenones. no activity could be detected with any of the substrates. S. coli. longa. flavonoids or stilbenes). Curcuminoids are pharmaceutically important compounds isolated from the herb Curcuma longa. Enzyme assays with all sorts of candidates failed. were observed only with unsaturated phenylpropanoid-CoAs. Journal of Biological Chemistry 284. Hölscher. With all other substrates. T. (2009) publication.. No activity was found with aromatic starter CoA-esters. S. . The simplest model for the initial reaction in diarylheptanoid biosynthesis predicts a phenylpropanoid-CoA as starter and a single condensation reaction to a diketide.Curcumin Synthesis in Curcuma longa: Two Cooperating Enzymes 16/03/11 12:23 PM of the Katsuyama et al. C-Methylated Flavonoids: more.. The other.. the experiments with Wdf2 and Wdf3 from Wachendorfia thyrsiflora so far do not provide any results suggesting that one or both of these proteins might correspond to the CURS functions identified in the C.does not really belong here: it is actually one enzyme with two condensations: more.. The availability of the substrates and the expression levels of the three different enzymes capable of curcuminoid synthesis with different substrate specificities might influence the composition of curcuminoids in the turmeric and in different cultivars.g. in which DCS synthesizes feruloyl-diketide-CoA.01.. 2005. and the products were the results expected from one or/and two condensations. Schneider.. D. Return to top Links to other enzymes with one condensation reaction Benzalacetone Synthases . Wdf3: the recombinant protein was difficult to purify because it was poorly soluble. Return to top . Identification and characterization of multiple curcumin synthases from the herb Curcuma longa. named curcumin synthase (CURS). 2006. S. Return to text Brand.0. have a look at a recent relationship tree (click here for a PDF-file of the tree): The tree suggests that WtPKS1 forms a subgroup with the diketide-CoA synthase (DKS) from Curcuma longa. Horinouchi. longa system...Quinoline alkaloids: more.

including cell cycle (cyclin D1 and cyclin E). 22-27. One of the enzymes is probably involved in the biosynthesis. and phosphorylation of c-Jun N-terminal kinase. but itself not able to form diarylheptanoids.. Curcumin is a diferuloylmethane derived from the Indian spice. The activity of curcumin reported against leukemia and lymphoma. Sundaram. Assays for enzymes in the phenylpropanoid pathway identified the corresponding enzyme activities in protein crude extracts from leaf. Considering the recent scientific bandwagon that multitargeted therapy is better than monotargeted therapy for most diseases.. Curcumin: the Indian solid gold. allergies. M. and targeted therapies. a vascular endothelial cell growth factor blocker (e. ERBITUX.g. Here. and its cardiovascular effects. IL-1. and a modification step for modification of the flavanones by flavone synthase. breast cancer. and other chronic illnesses. and AP-1). Curcumin exhibits activities similar to recently discovered tumor necrosis factor blockers (e. Crews. M. isolation. Synthesis of unnatural flavonoids and stilbenes by exploiting the plant biosynthetic pathway in Escherichia coli. and pharmaceuticals. Traditional medicines provide fertile ground for modern drug development. H.. Horinouchi. C. Return Cooke. Germany. survival (PI3K/AKT pathway). N.5. sprains. but could not be obtained for the other components due to the limitations of the particle beam interface when analyzing volatile and semi-volatile compounds. shoot and rhizome tissues from ginger and turmeric. Naturally occurring phenalenones and related compounds. I. Turmeric.. antifungal. protein kinases. head and neck squamous cell carcinoma. C. Cell 130. Ho. demethoxycurcumin and bisdemethoxycurcumin. T. C.) accumulate at high levels in their rhizomes important pharmacologically active metabolites that appear to be derived from the phenylpropanoid pathway. little is known about the biosynthesis of these compounds. Funa. 2008.Curcumin Synthesis in Curcuma longa: Two Cooperating Enzymes 16/03/11 12:23 PM Jena.1. B. Type III polyketide synthases should be involved in the first steps of the biosynthesis. lung cancer.html Page 4 of 5 ... In ginger. Y. EGFR. Five commercial powdered turmeric samples were analyzed to identify major and minor components. arthritis. Mehta. the formation of linear diarylheptanoids. Biologisch-Pharmazeutische Fakultät. radiation. These enzymes included phenylalanine ammonia lyase. Journal of Chromatography A 740. genitourinary cancers. A. including 36 unnatural flavonoids and stilbenes.... Curcumin. gastrointestinal cancers. and curcumin.. 07743 Jena. G. coli with exogenously supplied carboxylic acids led to production of 87 polyketides. This investigation describes the identification of enzymes in the biosynthetic pathway leading to the production of these bioactive natural products. R. 153-190. Members of the Zingiberaceae such as turmeric (Curcuma longa L. Since the time of Ayurveda (1900 Bc) numerous therapeutic activities have been assigned to turmeric for a wide variety of diseases and conditions. TNF.biologie.. IL-6.. 133-164. Despite their importance.. not only for health care but also for the preservation of food and as a yellow dye for textiles. capsaicin. B. derived from the plant Curcuma longa. HERCEPTIN).. and anticancer activities and thus has a potential against various malignant diseases. This work contains in addition to the characterization of the proteins by enzyme assays also hints to the nature of a second involved enzyme.. N. what are the active principles in them and how do they mediate their effects against cancer is perhaps best illustrated by curcumin. p-coumaroyl quinate transferase. are due to curcumin. 2006. Curcumin and cancer: An "old-age" disease with an "age-old" solution. Hartman. Return Anand. P. Journal of Cardiovascular Pharmacology and Therapeutics 14. 769-774. and sarcoma reflects its ability to affect multiple targets. Molecular understanding and modern application of traditional medicines: triumphs and trials. 51-63. diabetes. 2017-2029... EI mass spectra for the volatile components were obtained by direct thermal desorption-gas chromatography-mass spectrometry (DTD-GC-MS). These effects are mediated through the regulation of various transcription factors..uni-freiburg. apoptosis (activation of caspases and down-regulation of antiapoptotic gene products). R. 1-75. wounds. these compounds are the gingerols. and its structure as diferuloylmethane was determined in 1910. was first isolated almost two centuries ago.de/data/bio2/schroeder/Curcumin_Biosynthesis. R. and that life style plays a major role in the development of most cancers is now well recognized. but first they must pass along a pathway of discovery. Incubation of the recombinant E. Edwards.1. These included a substrate synthesis step for CoA esters synthesis from carboxylic acids by 4-coumarate:CoA ligase. N. human epidermal growth factor receptor blockers (e. that are probably involved in the defense against pathogens. C.. pulmonary. Rosen. 1996. HUMIRA..g. Return Srivastava. Characterization of powdered turmeric by liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry. Three enzymes were analyzed and investigated with regard to their involvement in the biosynthesis. proliferation (HER-2. chemotherapy. L. anti-inflammatory. and liver disorders. a derivative of turmeric used for centuries to treat a wide variety of inflammatory conditions. Return to text Ramirez-Ahumada. in turmeric these are the curcuminoids. J.. T. G. growth factors. invasion (MMP-9 and adhesion molecules). Studies need to be done in humans to define the potential of curcumin in limitation of cardiac injury and preservation of cardiac function following ischemia. The separation was accomplished on an octadecyl stationary phase using a mobile phase consisting of 50 mM ammonium acetate with 5% acetic acid and acetonitrile as the organic modifier. B. antiviral.. a polyketide synthesis step for conversion of the CoA esters into flavanones by chalcone synthase and chalcone isomerase.. Gang. 613-621. triptolide. Thus an "old-age" disease such as cancer requires an "age-old" treatment..01. 2007. p38 mitogen activated protein kinase and signal transducer and activator of transcription-3. Aggarwal.. Return to text Katsuyama. Advances in Experimental Medicine and Biology 595.. Return to text Corson. A host of studies in in vitro and in vivo models of cardiac injury show that curcumin treatment reduces reactive oxygen species generation. R. and mechanistic studies before eventual deployment in the clinic. M.. Return to text Hiserodt. Jhurani. 2007b. pains. There has been a surge of research in its anti-inflammatory and antioxidative properties. and ENBREL). turmeric (popularly called "curry powder") that has been shown to interfere with multiple cell signaling pathways. and gastrointestinal systems.. curcumin can be considered an ideal "Spice for Life". Timmermann. we highlight the challenges along this route. which gives the yellow color to turmeric. Thermospray mass spectra were obtained for all of the components. Recent studies in models of pressure overload show that curcumin can reduce cardiac remodeling by altering reninangiotensin-system-transforming growth factor 1 and collagen axis. current treatments usually involve poisonous mustard gas.. and into stilbenes by stilbene synthase. and 5-LOX). polyketide synthases.. No Abstract available. COX-2. as well as three other major components and numerous minor components. Malani. Curcumin has been shown to exhibit antioxidant. Extensive research within the last half century has proven that most of these activities. Return to text Aggarwal. and other enzymes. Cancer is primarily a disease of old age. Fortschritte der Chemie organischer Naturstoffe 40. melanoma. 2009. Miyahisa.g. ovarian cancer. Wachendorfia thyrsiflora (Haemodoraceae) contains a group of secondary metabolites called phenylphenalenones. including those of the skin. celastrol.. once associated with turmeric. Particle beam EI-mass spectra were obtained for the curcuminoids. Phytochemistry 67. Chemistry & Biology 14. Biosynthesis of curcuminoids and gingerols in turmeric (Curcuma longa) and ginger (Zingiber officinale): identification of curcuminoid synthase and hydroxycinnamoyl-CoA thioesterases.. G. monocyte adhesion to activated endothelial cells.) and ginger (Zingiber officinale Rosc. REMICADE. The developed HPLC method allows the separation of curcumin. p-coumaroyl shikimate transferase.0. angiogenesis (VEGF). Ichikawa. D. is a gold-colored spice commonly used in the Indian subcontinent. focusing on the compounds artemisinin. Sundaram.. flavanone 3beta-hydroxylase and flavonol synthase. W. Cancer Letters 267.. While plant-based formulations have been used to treat cancer for centuries. J. B. Kunnumakkara. 1980. inflammatory cytokines. Alzheimer's disease. B. Curcumin (diferuoylmethane) is the active ingredient of turmeric (Curcuma longa). cosmetics. caffeic acid O- http://www. AVASTIN). antibacterial. ERLOTINIB. Fürstengraben 26.. T. aches. C. The artificial biosynthetic pathway included three steps. While traditional plant-derived medicines are safe. These alterations lead to preservation of myocardial function following ischemic or biochemical insult to the heart. neurological cancers.g. This work deals with the isolation of polyketide synthases from root cultures of Wachendorfia thyrsiflora and their characterization. S.. B. Flavonoids and stilbenes have attracted much attention as potential targets for nutraceuticals. and GEFTINIB). 2007. We have developed a system for producing "unnatural" flavonoids and stilbenes in Escherichia coli. This system is promising for construction of a larger library by employing other polyketide synthases and modification enzymes. Currying the heart: curcumin and cardioprotection. S.. and a HER2 blocker (e. T. metastasis (CXCR-4) and inflammation (NF-?B.. and subsequent downstream signals..

[1. D. thereby potentially playing a regulatory role in the biosynthesis of these compounds.2009: Update on reference 05. and acridones are closely related plant-specific polyketide synthases. 1973. and -3. especially in ginger tissues. All crude extracts possessed activity for all of these enzymes. A. in which two cinnamate units condense with one malonate unit. stilbenes. and degradation of curcumin.. Tetrahedron Letters 40. Trends in Plant Science 2. the pigment of Curcuma Ionga rhizome.14 C]phenylalanine were incorporated into curcumin without scrambling of the label. Ionga.08. D. A. Return to text Roughley. Return to text Return to top File History : 21.5dione].de/data/bio2/schroeder/Curcumin_Biosynthesis. J.. http://www. 05. Return to text Schröder. In administration of labelled precursors to C. suitable for biosynthetic work. Recent results suggest that they belong to a family of condensing enzymes that catalyze the initial key reactions in the biosynthesis of several biologically and pharmaceutically interesting substances.. The product range is even more extended by modification of reaction intermediates.. These activities may shunt phenylpropanoid pathway intermediates away from the production of curcuminoids and gingerols. and supplied to C. [ 3 H]-4-Hydroxy-3-methoxy-. -4-hydroxy-..1.. However.04.. P.. suggesting that the protein family is much older than previously assumed. and which were found to be present at high levels in all tissues.2009: Link to application of two-component system to phenylphenalenone biosynthesis 30. The enzymes synthesizing chalcones..2009: Link to new relationship tree: click here for a PDF-file 24. [1and 2.. 23792388. characterisation.. with particular reference to curcumin [1.. This result was explained by the identification of thioesterase activities that cleaved phenylpropanoid pathway CoA esters. Diarylheptanoids.01. 1971. 373-378. no gingerol synthase activity could be identified. although none was utilised quite as efficiently as phenylalanine.uni-freiburg. (2009b).html Page 5 of 5 .biologie. the problems of the biosynthesis. Whiting. No Abstract available.4-dihydroxy-cinnamic acids were prepared. and caffeoyl-CoA O-methyltransferase. which were evaluated because of their potential roles in controlling production of certain classes of gingerols and curcuminoids.05. The results of polyketide synthase assays showed detectable curcuminoid synthase activity in the extracts from turmeric with the highest activity found in extracts from leaves. are reported. Return to text Roughly.5. 1997. Perkin Transactions 1.1. the results do not provide satisfactory support for the expected biosynthetic scheme. P. 3741-3745. The biogenesis of natural diarylheptanoids is discussed.7-bis-(4-hydroxy-3-methoxyphenyl)hepta-1. Ionga with [14 C]phenylalanine. and the fractional distribution of label along the heptane chain was determined. J. Other interpretations are discussed. A family of plant-specific polyketide synthases: facts and predictions.14 C]-Acetate and -malonate were also incorporated. Journal of the Chemical Society. J.6-diene-3.and 3. Experiments in the biosynthesis of curcumin.0. The first two cinnamic acids are incorporated into curcumin significantly better than the last. Recent analysis has revealed that related sequences occur in bacteria.Curcumin Synthesis in Curcuma longa: Two Cooperating Enzymes 16/03/11 12:23 PM methyltransferase.2009: Design of page . with the exception of polyketide synthases..03. Methods for the isolation..04.2009: Publication update: Identification of two more CURS-type enzymes in Curcuma longa: Katsuyama et al. Whiting.