Actinorhodin synthesis

A 26-kb gene cluster encoding enzymes for synthesis of the blue antibiotic actinorhodin by Streptomyces coelicolor has been cloned and sequenced.332337 The three large 10-kb genes required for formation of the broad-spectrum antibiotic erythromycin by Saccharopolyspora erythraea have also been cloned and sequenced.337 339 In both cases, the genes... 

Figure 7 Cell-free biosynthesis of SEK4, SEK4b, and DMAC. A strain of Streptomyces coelicolor in which the actinorhodin-minimal PKS genes had been overexpressed, produced both SEK4 and SEK4b. Expression of the KR, ARO, and CYC genes in addition to the minimal PKS resulted in the biosynthesis of DMAC. Synthesis of SEK4 and SEK4b has also been achieved using purified proteins in vitro.

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. 

A-L Matharu, RJ Cox, J Crosby, KJ Byrom, TJ Simpson. MCAT is not required for in vitro polyketide synthesis in a minimal actinorhodin polyketide synthase from Streptomyces coelicolor. Chem Biol 5 699-712, 1998. 

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 first synthesis of a dimeric pyranonaphthoquinone 225 which is related to naturally occurring biologically active compounds such as actinorhodin and crisamicin includes the double Fries rearrangement of the bis-ether 224 as one of the stages (equation 102). 

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]. 

Fig. 6. In vitro synthesis of actinorhodin biosynthetic intermediates and its shunt metabolites from acetyl CoA and malonyl CoA by the ActIORFI,2,3 polyketide synthase complex, the Actlll ketoreductase, the ActVII aromatase, ActIV cyclase, and the TcmO methyltransferase...

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