Polyketide folding mode

The overall biosynthetic pathway to the tetracychnes has been reviewed (74). Studies (75—78) utilising labeled acetate and malonate and nmr analysis of the isolated oxytetracycline (2), have demonstrated the exclusive malonate origin of the tetracycline carbon skeleton, the carboxamide substituent, and the folding mode of the polyketide chain. Feeding experiments using [1- 02] acetate and analysis of the nmr isotope shift effects, led to the location of... 

Remarkably, the same compound can be produced in different ways by different organisms. The best known example is probably the polyketide anthraquinone, chrysophanol 9, which occurs in both eukaryotes (higher plants, lichens, fungi and insects) and prokaryotes, but is produced through different folding modes of polyketide chains.10 Similarly, it has also been demonstrated that the biosynthesis of gibberellins involves different metabolic sequences in fungi and plants.11... 

Additional fused ring streptomycete polyketides shown in Figure 1 include the tetracyclic decaketides aclacinomycin (19), tetracenomycin C (20) and the angucycline vineomycin Ai (21), " which are formed by mode S folding. Although the incorporation of [ C2]acetate into cetocycline (13) and tetracenomycin C (20) does not appear to have been studied per se, the proposed folding mode of 13 is supported by the... 

Scheme 8 Putative rearrangements of mode S folded polyketides in the formation of PD 116198 and murayaquinone...

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 6 Apparent exceptions to mode S folding in polyketides from hybrid streptomycetes...

Sterigmatocystin (15) is both a carcinogenic hepatotoxin and a biosynthetic precursor to the important mycotoxin, aflatoxin, and, as such, its biosynthesis pathway has been studied quite extensively (607-608). This is purported to begin with a single C20 polyketide unit, which is folded in only one mode to form averufin (103) and then sterigmatocystin (15) (609). The authors provided evidence to support the identity of this compound through the synthesis of a common product from both it and from a... 

Several enrichment experiments established the primitive biogenetic precursors of the aflatoxins. The directional mode of folding of the original polyketide and the anomalous nature of the aflatoxin biosynthesis were deduced from NMR spectroscopy, hence illustrating the utility of this technique. The sequence of the aflatoxin biosynthesis was elucidated by the identification of advanced intermediates, the use of blocked mutants and enzyme inhibitors, and conversion of potential precursors by whole cell and cell-free systems into the aflatoxins. Certain facets of aflatoxin biosynthesis require further attention among these are the nature of the polyketide synthetase the exact mechanism by which primary metabolites induce the enzymes of aflatoxin production the loss of the C(6) phenolic hydroxy group during the conversion of the polyhydroxyanthraquinones (e.g., averufin. 

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