Aromatic polyketide synthases

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

CW Carreras, C Khosla. Purification and in vitro reconstitution of the essential protein components of an aromatic polyketide synthase. Biochemistry 37 2084-2088, 1998. 

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

C Bisang, PF Long, J Cortes, J Westcott, J Crosby, A-L Matharu, RJ Cox, TJ Simpson, J Staunton, PF Leadlay. A chain initiation factor common to both modular and aromatic polyketide synthases. Nature 401 502-505, 1999. 

Fig. 2a-d. The major architectural paridigms of fatty acid and polyketide synthases. Relationships between genes encoding a bacterial aromatic polyketide synthases, b eukaryotic fatty acid synthases and fungal polyketide synthases, c modular polyketide synthases, and d plant polyketide synthases... 

If identical plant and microbial polyketides are indeed derived by common or closely related pathvwiys, it would appear that higher plant species can produce both types of synthases required for the formation of mode F and mode S-cyclised fused ring polyketides. The biosynthesis of aloesaponarin II by steptomycetes is known to involve an iterative type IIPKS and, by analogy with other fungal aromatic polyketide synthases, it is likely that a type I PKS is responsible for the formation of chrysophanol. However, at present little is known of the nature of PKSs responsible for the formation of fused ring polyketides in plants. 

Type II polyketide synthases, also referred to as bacterial aromatic polyketide synthases (25) are involved in the biosynthesis of a number of clinically important bacterial aromatic polyketides products exhibiting antitumor or antibiotic activity, such as doxorubicin and oxytetracycline. As mentioned, type II synthases are evolutionarily and structurally related to type II FASs, which occurr as heteromultimeric complexes. In contrast to type I synthases however, where multiple catalytic sites occur within a given subunit, the polypeptides associated with type II synthase complexes are typically monofimctional and dissociable 20,30). 

Expression and Function of Aromatic Polyketide Synthase Genes in Raspberries Rubus idaeus sp.)... 

The starter unit represents an attractive site in the aromatic polyketide scaffold for introducing alternative chemical functionalities. Most aromatic polyketide synthases (PKSs) are primed by acetate through the decarboxylative condensation of malonyl-ACP. Nonacetate-primed PKSs have been sequenced and characterized. Precursor-directed biosynthesis and heterologous recombination of initiation and elongation modules have led to the engineered biosynthesis of completely new aromatic polyketide scaffolds containing novel starter units, as well as the regioselective modification of known aromatic polyketides. 

McDaniel,R., S.Ebert-Khosla, H.Fu, D.A.Hopwood and C.Khosla (1994a). Engineered biosynthesis of novel polyketides influence of downstream enzyme on the catalytic specificity of a minimal aromatic polyketide synthase. Proc. Natl. Acad. Sci USA 91 11542-11546. 

C. Khosla, Ketosynthases in the initiation and elongation modules of aromatic polyketide synthases have orthogonal acyl carrier protein specificity, Biochemistry 2003, 42, 6588-6595. 

McDaniel R, Ebert-Khosla S, Hopwood DA, Khosla C (1993) Engineered biosynthesis of novel polyketides manipulation and analysis of an aromatic polyketide synthase with improven catalytic specificities. J Am Chem Soc 115 11,671-11,675... 

Fig. 2A-D. Representatives of aromatic polyketide metabolites produced by aromatic polyketide synthases from A, B bacteria C fungi D plants...

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