Production of polyketides

Abstract

Recombinant host cells that comprise recombinant DNA expression vectors that drive expression of a product and a precursor for biosynthesis of that product can be used to produce useful products such as polyketides in host cells that do not naturally produce the product or produce the product at low levels due to the absence of the precursor or the presence of the precursor in rate limiting amounts.

1 . A recombinant polyketide synthase gene that encodes a loading module comprising a KS Q  domain, an AT specific for ethylmalonyl CoA, and an ACP domain.  
     
     
         2 . A host cell that comprises the recombinant polyketide synthase gene of  claim 1 , wherein said host cell further comprises a recombinant gene selected from the group consisting of recombinant ccr and icm genes.  
     
     
         3 . A method for the production of 14,15-propenylerythromycin and/or the corresponding 14,15-propenyl-6-deoxyerythronolide B, which comprises culturing a recombinant host cell that expresses isobutyryl CoA mutase, valine dehydrogenase, butyryl CoA dehydrogenase, and 6-deoxyerythronolide polyketide synthase.  
     
     
         4 . The method of  claim 3 , wherein said host cell is a  Saccharopolyspora erythraea  host cell.  
     
     
         5 . The method of  claim 4 , wherein said host cell does not express a functional eryM gene product.  
     
     
         6 . The method of  claim 3 , wherein said butyryl CoA dehydrogenase is expressed from a gene isolated from  Clostridium acetobutylicum  or  Mycobacterium tuberculosis  (fadE25).