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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.

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The enzymes

1. DCS ( Diketide-CoA Synthase):

That enzyme showed very little or no activity with cinnamoyl-CoA, 4-coumaroyl-CoA, or feruloyl-CoA, if the products were analyzed with the standard
procedures, i.e. extraction with organic solvent and subsequent analysis. However, 4-Coumaroyl-CoA led at least to a detectable low production of
benzalacetone, suggesting that the enzyme carried out only one condensation. The decisive point to detect the enzyme activity: do the analysis directly from the
incubation, i.e. do not use acidification or extraction with ethylacetate. When the analysis was done directly with the incubation mixture: it turned out that the
CoA-esters had been converted to the diketidyl-CoAs, indicating that the enzyme in fact carried out only one condensation with malonyl-CoA, and, most
importantly, that it released the diketide CoA-ester rather than a diketide acid (which is likely to be decarboxylated non-enzymatically to the ketone). The reaction
was very efficient with feruloyl-CoA, the best substrate, suggesting that the modifications leading from 4-coumarate to ferulate residues was done on the
phenylpropanoid level, not at the level of the curcuminoids. No activity at all was found with cinnamoyl-CoA. Interestingly, the kinetics of the enzyme with
feruloyl-CoA suggested that the substrate was an allosteric regulator of the activity, a point that could be important for the cooperation with the subsequent
enzyme, CURS.
2. CURS (Curcumin Synthase):
Incubations of that enzyme with cinnamoyl-CoA led to no products, but 4-coumaroyl-CoA and feruloyl-CoA gave trace amounts of curcuminoids. The results
with DCS suggested that diketidyl-CoAs could be the 'real' substrates, and therefore the authors synthesized a NAC (N-acetylcysteamine) derivative for
cinnamoyl-diketide (certainly not the optimal choice, but the synthesis was the simplest feasible option). Incubations of CURS with starter substrates and the
cinnamoyl-diketide-NAC in fact led to curcuminoid formation. Of course, the most interesting experiment was the co-incubation of DCS and CURS, in assays
simply containing feruloyl-CoA and malonyl-CoA. The experiment revealed an efficient production of curcumin, a very satisfying result, indeed.

Taken together, the results indicate that curcumin in Curcumal longa is synthesized by the cooperation of two different type III PKS. That is quite interesting
in several points:

It shows that C. longa uses two enzymes, each carrying out only one condensation, rather than a single enzyme using two different chain extenders, as
suggested for the unusual enzyme from rice (more...) that has no known physiological function,
The CURS reaction raises an interesting question: which is in this case the starter, which is the extender? That is not quite trivial because it is not necessarily
4-coumaroyl-CoA; it could also be the diketide CoA: this is of course not only the product of the first condensation, but also the starter substrate for the next
condensation in all type III PKS reactions carrying out more than one condensation. However, 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- or NAC-activated molecule).
Both DCS and CURS use feruloyl-CoA as starter substrate, i.e. they might compete for the same substrate. 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.

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Update on new CURS-type enzymes

A recent publication (Katsuyama et al., 2009b) described the molecular and functional characterization of two more CURS-type enzymes, CURS2 and CURS3 (the first
CURS was renamed to CURS1). Both were closely related to each other and CURS1; see the relationship tree. Nevertheless, they revealed interesting differences in
the substrate preferences, 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.

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A generalization of the 'two enzyme principle' ?

There are other natural products that possibly share the same basic biosynthetic reactions, like gingerol (Ginger), and most important in this context, the
phenylphenalenones in Wachendorfia thyrsiflora, and a candidate enzyme for the first reaction ('DCS' function) has been described (more..., Brand et al., 2006). If the
findings with C. longa can be generalized: In W. thyrsiflora a protein with the 'CURS' function had not been identified, but the databases actually do not only contain the
characterized DCS candidate (AY727928, WtPKS1, called Wdf1), but two more sequences: AY739910 (= Wdf2) and AY973271 (= Wdf3). These latter two are about
95% identical, but the values are much lower with WtPKS1 (about 55-60% identity). Could this be candidates for a CURS function? This is proposed in the discussion

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of the Katsuyama et al. (2009) publication. The Brand et al. (2006) paper does not provide information on the two other proteins, but the published PhD thesis of Silke
Brand (Brand, 2005, in German) does contain additional information that of course was not easily accessible to the Japanese group. The results in brief (Brand, 2005):
Wdf2: a recombinant protein was expressed in E. coli. It was soluble and could easily be purified. Enzyme assays with all sorts of candidates failed; no activity
could be detected with any of the substrates. Most importantly, activity was also not detected in incubations with diketide-NAC derivatives, or in assays
containing the expected substrates and both Wdf1 and Wdf2. In particular these latter negative results would not be expected for a CURS function.
Wdf3: the recombinant protein was difficult to purify because it was poorly soluble. Nevertheless, the activities could be tested. There was activity with linear
aliphatic CoA-esters (C3 to C8 CoA-esters), and the products were the results expected from one or/and two condensations. No activity was found with aromatic
starter CoA-esters. 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.

Taken together, 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. longa system.
However, 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, 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.

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Links to other enzymes with one condensation reaction

Benzalacetone Synthases
- Raspberry (Rubus idaeus): more...
- Rhubarb (Rheum palmatum): more...
C-Methylated Flavonoids: more...
Diketide Derivatives
- Phenylphenalenones: more...
- Curcuminoids:
- Curcuminoid biosynthesis by two cooperating enzymes in Curcuma longa: more...
- Curcuminoid synthase in rice:
- does not really belong here: it is actually one enzyme with two condensations: more...
Proposals
- Benzylacetone: more... (Note: this is different from benzalacetone !!)
- Quinoline alkaloids: more...

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.

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.
Curcuminoids found in the rhizome of turmeric, Curcuma longa, possess various biological activities. Despite much attention regarding the biosynthesis of
curcuminoids because of their pharmaceutically important properties and biosynthetically intriguing structures, no enzyme systems have been elucidated. Here
we propose a pathway for curcuminoid biosynthesis in the herb C. longa, which includes two novel type III polyketide synthases (PKSs). One of the type III
PKSs, named diketide-CoA synthase (DCS), catalyzed the formation of feruloyl-diketide-CoA by condensing feruloyl-CoA and malonyl-CoA. The other, named
curcumin synthase (CURS), catalyzed the in vitro formation of curcuminoids from cinnamoyl-diketide-N-acetylcysteamine (a mimic of the CoA ester) and feruloyl-
CoA. Co-incubation of DCS and CURS in the presence of feruloyl-CoA and malonyl-CoA yielded curcumin at high efficiency, although CURS itself possessed
low activity for the synthesis of curcumin from feruloyl-CoA and malonyl-CoA. These findings thus revealed the curcumin biosynthetic route in turmeric, in which
DCS synthesizes feruloyl-diketide-CoA, and CURS then converts the diketide-CoA esters into a curcuminoid scaffold.
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Katsuyama, Y., Kita, T., Horinouchi, S., 2009b. Identification and characterization of multiple curcumin synthases from the herb Curcuma longa. FEBS
Letters 583, 2799-2783.
Curcuminoids are pharmaceutically important compounds isolated from the herb Curcuma longa. Two additional type III polyketide synthases, named CURS2
and CURS3, that are capable of curcuminoid synthesis were identified and characterized. In vitro analysis revealed that CURS2 preferred feruloyl-CoA as a
starter substrate and CURS3 preferred both feruloyl-CoA and p-coumaroyl-CoA. These results suggested that CURS2 synthesizes curcumin or
demethoxycurcumin and CURS3 synthesizes curcumin, bisdemethoxycurcumin and demethoxycurcumin. 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.
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Brand, S., Hölscher, D., Schierhorn, A., Svatos, A., Schröder, J., Schneider, B., 2006. A type III polyketide synthase from Wachendorfia thyrsiflora and
its role in diarylheptanoid and phenylphenalenone biosynthesis. Planta 224, 413-428.
Chalcone synthase (CHS) related type III plant polyketide synthases (PKSs) are likely to be involved in the biosynthesis of diarylheptanoids (e.g. curcumin
and polycyclic phenylphenalenones), but no such activity has been reported. Root cultures from Wachendorfia thyrsiflora (Haemodoraceae) are a suitable source
to search for such enzymes because they synthesize large amounts of phenylphenalenones, but no other products that are known to require CHSs or related
enzymes (e.g. flavonoids or stilbenes). 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. It was named WtPKS1 (W. thyrsiflora polyketide synthase 1). The purified recombinant protein accepted a large variety of aromatic
and aliphatic starter CoA esters, including phenylpropionyl- and side-chain unsaturated phenylpropanoid-CoAs. The simplest model for the initial reaction in
diarylheptanoid biosynthesis predicts a phenylpropanoid-CoA as starter and a single condensation reaction to a diketide. Benzalacetones, the expected release
products, were observed only with unsaturated phenylpropanoid-CoAs, and the best results were obtained with 4-coumaroyl-CoA (80% of the products). With all
other substrates, WtPKS1 performed two condensation reactions and released pyrones. 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.
Return to text or go to a more detailed discussion
Request a reprint
Brand, S., 2005. Pflanzliche Polyketidsynthasen des Typ III in Wachendorfia thyrsiflora (Haemodoraceae). PhD Thesis, Friedrich-Schiller-Universität

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Jena, Biologisch-Pharmazeutische Fakultät, Fürstengraben 26, 07743 Jena, Germany.

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

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methyltransferase, and caffeoyl-CoA O-methyltransferase, which were evaluated because of their potential roles in controlling production of certain classes of
gingerols and curcuminoids. All crude extracts possessed activity for all of these enzymes, with the exception of polyketide synthases. 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. However,
no gingerol synthase activity could be identified. This result was explained by the identification of thioesterase activities that cleaved phenylpropanoid pathway
CoA esters, and which were found to be present at high levels in all tissues, especially in ginger tissues. These activities may shunt phenylpropanoid pathway
intermediates away from the production of curcuminoids and gingerols, thereby potentially playing a regulatory role in the biosynthesis of these compounds.
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Roughley, P. J., Whiting, D. A., 1973. Experiments in the biosynthesis of curcumin. Journal of the Chemical Society, Perkin Transactions 1, 2379-
2388.
The biogenesis of natural diarylheptanoids is discussed, with particular reference to curcumin [1,7-bis-(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-
dione], the pigment of Curcuma Ionga rhizome. Methods for the isolation, characterisation, and degradation of curcumin, suitable for biosynthetic work, are
reported. In administration of labelled precursors to C. Ionga, [1- and 3- 14 C]phenylalanine were incorporated into curcumin without scrambling of the label. [1-
and 2- 14 C]-Acetate and -malonate were also incorporated, and the fractional distribution of label along the heptane chain was determined; the results do not
provide satisfactory support for the expected biosynthetic scheme, in which two cinnamate units condense with one malonate unit. Other interpretations are
discussed. [ 3 H]-4-Hydroxy-3-methoxy-, -4-hydroxy-, and -3,4-dihydroxy-cinnamic acids were prepared, and supplied to C. Ionga with [14 C]phenylalanine. The
first two cinnamic acids are incorporated into curcumin significantly better than the last, although none was utilised quite as efficiently as phenylalanine.
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Roughly, P. J., Whiting, D. A., 1971. Diarylheptanoids; the problems of the biosynthesis. Tetrahedron Letters 40, 3741-3745.
No Abstract available.
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Schröder, J., 1997. A family of plant-specific polyketide synthases: facts and predictions. Trends in Plant Science 2, 373-378.
The enzymes synthesizing chalcones, stilbenes, and acridones are closely related plant-specific polyketide synthases. 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. Recent analysis has revealed that related sequences occur in bacteria,
suggesting that the protein family is much older than previously assumed.
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File History :

21.08.2009: Publication update: Identification of two more CURS-type enzymes in Curcuma longa: Katsuyama et al. (2009b),
05.05.2009: Link to application of two-component system to phenylphenalenone biosynthesis
30.04.2009: Update on reference
05.04.2009: Link to new relationship tree: click here for a PDF-file
24.03.2009: Design of page

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