Tetracenomycin aromatic polyketide

A. Actinorhodin, Tetracenomycin, Doxorubicin, and Other Bacterial Aromatic Polyketide Synthases... 

Figure 10 Examples of unnatural aromatic polyketides. Libraries of aromatic poly-ketides have been generated using combinations from the actinorhodin, tetracenomycin, frenolicin, griseusin, and whiE spore pigment gene clusters.

Figure 3 Aromatic PKS gene clusters and actinorhodin biosynthesis. Partial gene clusters for the polyketides actinorhodin (act), tetracenomycin (tcm), and doxorubicin (dps) are shown. Reconstitution of combinations of act genes in a PKS clean host have led to a proposed pathway by which the early stages of actinorhodin biosynthesis occur.

Using these techniques (combinatorial biosynthesis) with streptomycetes, the polyketides have now been investigated, including not only the macrolides (e. g., erythromycin) but also polycyclic aromatic compounds (e.g., actinorhodin, tetracenomycins). The formation of hybrids can alter not only the size of the poly ketide skeleton, its stereochemistry or its functionality but also enzyme systems of the later steps of biosynthesis such as, e. g., oxygenases or glycosy Itrans-ferases. In practice major difficulties arise because each intermediate in the biosynthetic sequence is a substrate for the following enzyme thus if a changed substrate is not accepted by the respective enzyme the biosynthesis breaks down. 

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