Actinorhodin aromatic polyketide

J Dreier, AN Shah, C Khosla. Kinetic analysis of the actinorhodin aromatic polyketide synthase. J Biol Chem 274 25108-25112, 1999. 

From the cultures of streptomycetes were isolated anthacyclinones like aklavi-none. Various aromatic polyketide antibiotics produced by fungi and bacteria have quinoid structures, for example, doxorubicin, rhodomycin, and actinorhodin. ... 

Figure 11.1 Representative secondary metabolites produced by Streptomyces ceolicolor and other microorganisms, including aromatic polyketides actinorhodin and tetrohydroxynaphthalene (a), side-rophore desferrioxamines (b), polyunsaturated fatty acid eicosapentaenoic acid (c) and terpenoids beta-...

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.

CW Carreras, R Pieper, C Khosla. Efficient synthesis of aromatic polyketides in vitro by the actinorhodin polyketide synthase. J Am Chem Soc 118 5158-5159, 1996. 

Type II PKSs, on the other hand, carry out polyketide synthesis in an iterative manner, and are responsible for the biosynthesis of aromatic polyketides, as exem-phfied by the actinorhodin PKS (Pig. 5.2 C) and R1128 PKS (Pig. 5.2D). Each active site occurs as a distinct monofunctional protein, and the entire PKS complex is used for aU the synthesis steps. It should be noted that that some PKSs have features of both type 1 and type 11 categories. Por a review of this topic, see Ref. [39]. 

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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