Polyketide synthase fungi

The second largest class of compounds reported from macroalgae is the polyketides, which comprise approximately a quarter of known algal compounds (Blunt et al. 2007). Polyketides are polymers of acetate (C2) and occasionally propionate (C3) and are very similar to fatty acids in their biosynthetic origin. Polyketides can be found in plants, animals, bacteria, and fungi. With a range of activities as broad as their structures, the polyketides are a diverse family of natural products classified based upon the polyketide synthases (PKSs) responsible for their biosynthesis, primarily type I and type II. 

Native CHS is a homodimer with subunits of 40 to 44kDa. The structure of the protein produced from the CHS2 cDNA of M. sativa has been determined and the residues of the active site defined. It belongs to the polyketide synthase (PKS) group of enzymes that occur in bacteria, fungi, and plants, and is a type III PKS. All the reactions are carried out at a single active site without the need for cofactors. 

Natural products represent a diversity of chemical compounds with varied biological activities. Natural products are an important source of novel pharmaceuticals as well as agricultural pesticides (1,2). Natural products are derived from a number of pathways that create basic scaffolds that are further modified by various tailoring enzymes to create the wide diversity of structures that exist in nature. Polyketide synthases are responsible for the synthesis of an array of natural products including antibiotics such as erythromycin in bacteria (3) and mycotoxins such as aflatoxin in fungi (4). Furthermore, in plants they are part of the biosynthetic machinery of flavonoids, phytoalexins, and phenolic lipi (5,6). 

Two differences exist between fatty acid and complex polyketide syntheses (Fig. 2). First, in fatty acid synthesis, synthase uses only malonyl moieties as extender units to build an acyl chain. In general, acetate is used as the starter unit in vertebrate fatty acid synthase, but bacterial fatty acid synthase may use a branched-chain carboxylic acid as the starter unit because bacterial fatty acids sometimes contain branched-chain fatty acids. In contrast, polyketide synthesis in bacteria uses malonyl, methylmalonyl, and ethylmalonyl units as extenders. In the polyketide synthase, respective extender units are used at every step of the condensation. The polyketide synthase in fungi uses malonyl units as extenders and methyl groups at a positions are added by C-methylation using 5-adenosyl-L-methionine. 

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

Such complexes include fatty acid synthases (FASes), elongases (ELSes) and polyketide synthases (PKSes) which can fimction individually or in concert. FAS synthesizes the 16 and 18 carbon acyl chains of membrane lipids as well as those of the plant cutin and suberin monomers. ELSes use these acyl chains as primers to synthesize longer ones for storage lipids in some seeds and for cuticular and epicuticular waxes. PKSes participate in a wide range of secondary metabolic pathways. In plants chalcone synthase contributes to the carbon skeleton of the flavonoids, in fungi and bacteria, especially... 

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