Production of polyketides

Abstract

Recombinant host cells of the suborder Cystobacterineae containing recombinant expression vectors that encode heterologous PKS genes can produce polyketides synthesized by the PKS enzymes encoded on those vectors at high levels.

1 . A recombinant host cell of the suborder Cystobacterineae containing a recombinant expression vector that encodes a heterologous PKS gene and produces a polyketide synthesized by a PKS enzyme encoded on said vector.  
     
     
         2 . The host cell of  claim 1  selected from the group consisting of the genus  Myxococcus  or and the genus  Stigmatella.    
     
     
         3 . The host cell of  claim 2  that is a  Myxococcus  host cell.  
     
     
         4 . The host cell of  claim 2  that is a  Stigmatella  host cell.  
     
     
         5 . The host cell of  claim 3  that is selected from the group consisting of  M. stipitatus, M. fulvus, M. xanthus , and  M. virescens.    
     
     
         6 . The host cell of  claim 4  that is selected from the group consisting of  S. erecta , and  S. aurantiaca.    
     
     
         7 . The host cell of  claim 5  that is  Myxococcux xanthus.    
     
     
         8 . A recombinant DNA vector capable of chromosomal integration or extrachromosomal replication in a host cell of  claim 1 , said vector comprising at least a portion of a PKS coding sequence and capable of directing expression of a functional PKS enzyme in said host cell.  
     
     
         9 . A method for producing a polyketide in a host cell of the suborder Cystobacterineae, which polyketide is not naturally produced in said host cell, said method comprising culturing a host cell of  claim 1  under conditions such that a PKS gene encoded on the vector is expressed and said polyketide is produced.  
     
     
         10 . The recombinant host cell of  claim 1  that produces epothilone or an epothilone derivative.  
     
     
         11 . The host cell of  claim 10  that produces epothilones at equal to or greater than 10 mg/L.  
     
     
         12 . The host cell of  claim 10  that produces epothilones C and D but not A and B.  
     
     
         13 . The host cell of  claim 10  that produces epothilones A and B but not C and D.  
     
     
         14 . The host cell of  claim 10  that produces an epothilone derivative selected from the group consisting of 9-oxo-11-hydroxy-epothilone D; 9-hydroxy-11-oxo-epothilone D; and 9,11-dihydroxy-epothilone D.