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(Last modification: 05. March 2010)
Type III PKS in Polygonum cuspidatum
What are type III PKS? more...
From Wikipedia:
This plant is interesting because it has part of the traditional Chinese Medicine for ages , and therefore its ingredients have been under intensive investigation. Usually, the extracts from roots/rhizomes are used. The most well-known compounds are resveratrol and its glycosylated derivatives, of course, and many resveratrol preparations are more or less simply extracts from the roots/rhizomes. Actually, this seems to be the cheapest source of resveratrol. However, when using such extracts one should also consider that the plant tissue contains other secondary products; the most prominent (sometimes in the same concentrations as resveratrol!) appears to be emodin, an anthraquinone that is under intensive pharmacological investigation (see for example: Xiao et al., 2002; Chu et al., 2005; Zhang et al., 2006; Wang et al., 2007; Yi et al., 2007; Leu et al., 2008; Zhuang et al., 2008), and may be not harmless under certain conditions and taken in larger amounts. Looking in this context on polyketide synthases, one would expect that this plant contains at least two type III PKS, namely the standard chalcone synthase (CHS) and a resveratrol synthase (a stilbene synthase, STS). Actually, one could speculate on a third type III PKS that might be involved in the biosynthesis of the anthraquinone emodin. The databases indeed contain five distinguished entries for type III PKS (some others are likely duplicates); they are summarized in the Table below.
Two of these entries are associated with publications. One protein (PcPKS2, Ma et al., 2009a) was characterized as BAS (product benzalacetone, BA, one condensation with 4-coumaroyl-CoA), but actually, depending on the assay pH, the protein also revealed in vitro strong synthesis of 4-Coumaroyltriacetic acid lactone (CTAL, three condensations, release of lactone, more...) and bisnoryangonin (BNY, two condensations, more...). The pH dependence is shown in Fig. 1. Both CTALand BNY were often identified as byproducts of CHS and stilbene synthase (STS) reactions, but not with such high amounts and with such strong pH dependence. This is very much reminiscent of the BAS in Rheum palmatum, which showed a similar pH dependence: BA synthesis at high pH (pH 8), BNY synthesis at slightly acid pH (pH 6) (more...). A relationship tree (click here for PDF-file) indeed shows that the two proteins are closely related, in numbers: 83% identity at the protein level. It looks as if such pH dependence might be characteristic for BAS enzymes. The problem with Polygonum cuspidatum is that BA, CTAL, BNY, or their derivatives are not known from that plant. Strictly spoken, the enzyme so far should be called an orphan, i.e. an enzyme in search of a physiological function. The second protein characterized in a publication a bit later (PcPKS1, Ma et al., 2009b) revealed somewhat different properties. Like PcPKS2, PcPKS1 had BAS activity at alkaline pH, but in contrast to PcPKS2, it had a typical CHS activity at more physiological pHs (pH 7-8) (Fig. 1 below). The enzyme was therefore considered a CHS, but bi-functional because of its BAS activity. Actually, one would think from the comparison of the enzyme properties that PKS2 looks like a PKS1 which lost the capacity to carry out the Claisen condensation that distinguishes Naringenin from CTAL. The similarity goes a bit further: both are very unusual in the type III plant PKS family in having three introns in the gene, in the same positions; no other type III PKS appears to have three introns. Nevertheless, the protein sequence comparison indicated that they have diverged quite a bit, and a relationship analysis shows that they do not cluster on the same branch, but are quite distant from each other. PKS1 clusters with a CHS from P. cuspidatum (CHS2, see the Table above) that contains only one intron (cited in Ma et al., 2009a) and is only given in the databases . More interestingly, it is on the same branch with two CHS from Rheum palmatum (look at the PDF-file with the relationship tree).
Products of PKS1 and PKS2 from Polygonum cuspidatum, and the pH-dependence of their activities. NAR = naringenin (CHS activity); BA, benzalacetone (BAS activity), CTAL, 4-Coumaroyltriacetic acid lactone; BNY, bisnoryangonin. Data from Ma et al., 2009a and 2009b, but re-drawn and re-arranged (the publications do not show a direct comparison).
The databases contain two more P. cuspidatum type III PKS sequences (cited in Ma et al., 2009a, summarized in the Table above). One, annotated as STS, is indeed closely related to an STS from Rheum tataricum (Samappito et al., 2003) (see relationship tree). This protein should be a good candidate for the STS activity that must be present in P. cuspidatum. Interesting question The other type III PKS is annotated as putative STS, but it is interesting that it is closely related to the aloesone synthase (ALS) from Rheum palmatum, as is obvious also from the presence on a common branch in the relationship tree. The ALS carries out six condensations, starting from acetyl-CoA (more...). I am not aware of publications describing natural products in P. cuspidatum that could be derived from such PKS reaction. However, in this context it is interesting that emodin (and other anthraquinones) are major components of the extracts from roots/rhizomes. Their biosynthesis could be explained by a polyketide synthase reaction starting from acetyl-CoA/malonyl-CoA and carrying out seven condensations. Type III PKS have indeed been implicated in anthrone biosynthesis, in the monocotyledon Aloe arborescens (more...), and in the dicotyledon Hypericum perforatum (more...). It is tempting to venture a speculation that this P. cuspidatum protein might be a candidate for a key enzyme in emodin biosynthesis. . |
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