E. coli host cells that synthesize methylmalonyl CoA

摘要

The use of enzymes which catalyze the production of starter and extender units for polyketides is described. These enzymes may be used to enhance the yield of polyketides that are natively produced or polyketides that are rationally designed. By using these techniques, the synthesis of a complete polyketide has been achieved in E. coli. This achievement permits a host organism with desirable characteristics to be used in the production of such polyketides and to assess the results of gene shuffling. Particularly disclosed is a recombinant E. coli host cell that incorporates: i) a propionyl CoA Carboxylase ( pcc ) expression system comprising the pccB and accA2 genes from S. coelicolor wherein said pcc expression system produces an enzyme capable of synthesizing 2S-methylmalonyl CoA ; ii) at least one expression system for a modular polyketide synthase ( PKS ); and iii) at least one expression system for a phosphopantetheniyl transferase that phosophanthetheinylates the PKS . and uses thereof.