Octaketides

Norm ethyl dehydro - Dehydrogri seof ulvin 

Representatives of this group of polyketides are anthraquinone derivatives and ergochromes. In most of the anthraquinones the nucleus is substituted at C-1 and C-8 with hydroxy groups and may carry an additional hydroxy group at C-3 and a one-carbon side chain at C-6 (Table 34). Anthraquinones are easily reduced to anthrones/anthranols in a reversible reaction  

Ajithrone derivatives possess an activated CHg-group at position 10 and therefore are able to form C-glycosides at this position (see the formula of aloin). Most 

Single carbon bonds Unking two anthrone or anthraquinone moieties are common (cf. the formula of dicatenarin, fig. 79). 

The ergochromes are light yellow dimeric xanthone derivatives resembUng the anthraquinones in their pattern of substitution (Fig. 79). The two xanthone moieties (secalonic acids) are interUnked at the position 2. 

The largest and most important chemical class within this category comprises the anthraquinone and pre-anthraquinone pigments found in great variety in toadstools belonging to the genera Dermocybe, Cor-tinarius, Tricholoma and Leucopaxillus. 

Scrambling of label from I 2]acetate in ring C indicates that 

C-25 implies cleavage of an anthraquinone rather than an enthrone 

This latter result contrasts somewhat with studies on anthraquinone biosynthesis in Peniclllium islandicum.The syn-14 

This would appear to be the first detection of hicyclic intermediates in anthraquinone biosynthesis in microorganisms. 

However, two problems posed by these results are the required aldol condensation onto a mono-activated methyl rather than the usual doubly activated methylene and the incorporation into skyrin implies loss of ketide oxygen and subsequent reoxidation of the same, and now, unactivated position, which seems highly inefficient biosynthetically. Oxygen-18 studies to confirm the origins of 

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Aloe (Aloe arborescens) is a medicinal plant rich in aromatic polyketides such as pharmaceutically important aloenin (a hexaketide pyrone), aloesin (a heptaketide chromone), and barbaloin (an octaketide anthrone) (Fig. 4a). Pentaketide chromone synthase (PCS) and octaketide synthase (OKS) are novel plant-specific type III PKSs, which were obtained from the aloe plant by RT-PCR cloning using degenerate oligonucleotide primers based on the conserved sequences of known CHS enzymes [30-33]. The deduced amino acid sequences of PCS and OKS are 91% identical (368/403), and show 50-60% identity to those of other CHS superfamily type III PKSs of plant origin OKS shares 60% identity (240/403) with CHS from... 

Abe I, Oguro S, Utsumi Y, Sano Y, Noguchi H (2005) Engineered biosynthesis of plant polyketides chain length control in an octaketide-producing plant Type III polyketide synthase. J Am Chem Soc 127 12709-12716... 

Karppinen K, Hokkanen J, Manila S, Neubauer P, Hohtola A (2008) Octaketide-producing type III polyketide synthase from Hypericum perforatum is expressed in dark glands accumulating hypericins. FEBS J 275 4329-4342... 

Morita H, Kondo S, Kato R, Wanibuchi K, Noguchi H, Sugio S, Abe I, Kohno T (2007) Crystallization and preliminary crystallographic analysis of an octaketide-producing plant type III polyketide synthase. Acta Crystallograph Sect F Struct Biol Cryst Commun 63 947-949... 

MAT has stringent specificity toward malonyl-CoA, which is reflected in the exclusive utilization of malonyl extender units by Type n PKS 7 Together, these four enzymes consist of the smallest set of enzymes required for the synthesis of a complete polyketide chain. For example, the minimal PKS from the actinorhodin (act) biosynthetic pathway synthesizes an octaketide (Cjg) backbone from eight malonyl-CoA equivalents, the tetracenomycin (tan) minimal PKS synthesizes a decaketide (C20) backbone from ten equivalents of malonyl-CoA (Figure 8A), and the pradimycin (pms) minimal PKS synthesizes a dodecaketide (C24) backbone from twelve equivalents of malonyl-CoA. ... 

The Cj symmetrical macrodiolide elaiophylin (41) consists of two identical polyketide chains which are linked to a deoxyfucose at C-13 [83]. Here, it was assumed that macrodilactone formation is the last biosynthetic step, and only one glycosyl transfer step is necessary prior to lactonization. However, incorporation experiments with the complete (glycosylated) octaketide half 42 failed. Later, after changing the fermentation parameters, the asymmetrical mono-glycosyl derivative 43 was isolated, indicating that the two glycosyl transfer steps take place after generation of the macrodiolide 44 [83-85] (Scheme 16). 

Fig. 4. Polyketide biosynthesis by gene products of the act PKS cluster. Presence of the KS/AT, CLF, and ACP is sufficient for the production of two 16-carbon polyketides, SEK4 and SEK4b both in vivo [ 103] and in vitro [107]. In the presence of the act ketoreductase (KR), aromatase (ARO) and cyclase (CYC), the octaketide intermediate is converted into DMAC. DMAC can be converted into 8-methoxy DMAC both in vivo and in vitro through the S-adenosylmethionine (Adomet)-dependent action of the tcmO methyltransferase [207]...

PCS-catalyzed condensation of five molecules of malonyl-CoA to produce 5,7-dihydroxy-2-methyl chromone new to this plant (40). Another novel Aloe arborescens type III PKS that produces two hitherto unknown aromatic octaketides, SEK4 and SEK4b, has recently been reported (41). The application of plant cell cultures for the production of the polyketide hypericin from St. John s wort (Hypericum performatum, Hypericaceae) has been investigated (42). 

Figure 10 Conversion of malonyl-ACP to acetyl-ACP and polyketide production by KS/CLF mutants, (a) ESMS analysis of initial sample of malonyl-ACP before decarboxylation and after incubation with either (middle) KS(ala)/CLF(gln) (60 min), or (right) KS(gln)/CLF(ala) (1 min), (b) Time course of decarboxylation of malonyl CoA by KS(ala)/CLF(gln), and production of octaketides (SEK-4 + SEK-4b) from malonyl ACP by KS(cys)/CLF(ala), both in the presence (triangles) and absence (squares) of acetyl-ACP.

Another example of the possible simultaneous operation of both F and S cyclisation modes in the same plant species, is the formation of the naphthalene octaketides eleutherin (65) and eleutherinol (66) in Eleutherine bulbosa The structure of eleutherin corresponds to that of a mode F folded polyketide, whereas the cyclisation pathway originally proposed by Birch and Donovan for the biosynthesis of eleutherinol would require mode S folding, although its formation by rearrangement of an advanced eleutherin precursor is an alternative possibility. 

Figure 7 Apparent mode F and mode Sfoldedfused ring octaketides of higher plants...

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