Through extensive metabolic engineering, a team of researchers has produced a strain of Escherichia coli capable of synthesizing polyketides—the chemical building blocks for several blockbuster drugs. The soil bacteria that are currently used to produce polyketides are difficult to culture and are not amenable to genetic manipulation, creating a bottleneck in drug development. Polyketides produced in this manner include erythromycin, the immunosuppressant FK506, and lovastatin, enjoying total annual sales of over $10 billion. The researchers introduced genes encoding the three subunits of the polyketide synthase from the soil bacterium Saccharopolyspora erythraea into E. coli (Science, 291, 1790–1792, 2001). They then added genes to generate the precursors for the polyketides, while deleting genes for enzymes that would otherwise break down these cofactors. Using this approach, the scientists produced useful quantities of the core polyketide needed for erythromycin synthesis, and a polyketide not seen before. “We anticipate that E. coli could become a useful host for both production of commercial quantities of polyketides as well as to produce novel analogs,” says Chaitan Khosla, a researcher at Stanford University and senior author on the paper. Kosan Biosciences (Hayward, CA), which Khosla co-founded, is now working to develop the technology commercially.