Technology applied to Polyketide Engineering & Production  
 

technology may be readily applied to the production of polyketides. Polyketide products are of immense importance to the pharmacetical industry, accounting for annual sales of over $20 Billion, and including Zocor, Pravacol, Zithromax, Erythromycin, and many other well known and valuable drugs.

 
 

Polyketides are produced naturally by enzymes called polyketide synthases, (PKSs). A class of PKS, called ‘modular polketide synthases’, is of particular interest. There is a direct correspondence between the module sequence present in this type of PKS, in the parent gene that produces it, and in the polyketide whose production it controls. Careful modification of the DNA units (modules) of the parent gene will result in a corresponding predictable modification of the modular PKS, and of the resulting polyketide.

The resulting modified polyketide may retain important properties of the unmodified polyketide, but may also demonstrate certain enhanced properties.

Figure 1 shows this relationship between the DNA of the organism, the PKS, and the resulting polyketide. Scientists have been using this knowledge for the past decade to produce modified polyketides, in order to provide, for example, novel drugs.
 
 
   
  Figure 1. From DNA to drug  
 
 
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Problems with traditional assembly

Each repeating inter-module junction requires a separate restriction enzyme and corresponding engineered recognition sites.
Number of restriction enzymes is limited.
Random methods of plasmid modification cannot assure desired gene.
 
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What can technology bring to this?

Of course, the technology could be used to carry out piecemeal modifications to an existing polketide. However, since the Qxyz technology permits the assembly of a new parent gene and PKS de novo, it is possible for us to reverse engineer the desired parent gene of a new polyketide in its entirety. One can work back from the desired polyketide to the PKS, and hence to the parent gene that would be needed to create it. technology can then be used to assemble that gene, and the target product produced by the familiar methods of gene expression.

believes that this approach has enormous potential in its application to the engineering and production of new or modified polyketides, and in particular for the development and manufacture of valuable new drugs.

 
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