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Science 2 March 2001:
Vol. 291. no. 5509, pp. 1790 - 1792
DOI: 10.1126/science.1058092
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Reports

Biosynthesis of Complex Polyketides in a Metabolically Engineered Strain of E. coli

Blaine A. Pfeifer,1 Suzanne J. Admiraal,1 Hugo Gramajo,1* David E. Cane,4 Chaitan Khosla123dagger

The macrocyclic core of the antibiotic erythromycin, 6-deoxyerythronolide B (6dEB), is a complex natural product synthesized by the soil bacterium Saccharopolyspora erythraea through the action of a multifunctional polyketide synthase (PKS). The engineering potential of modular PKSs is hampered by the limited capabilities for molecular biological manipulation of organisms (principally actinomycetes) in which complex polyketides have thus far been produced. To address this problem, a derivative of Escherichia coli has been genetically engineered. The resulting cellular catalyst converts exogenous propionate into 6dEB with a specific productivity that compares well with a high-producing mutant of S. erythraea that has been incrementally enhanced over decades for the industrial production of erythromycin.

1 Department of Chemical Engineering,
2 Department of Chemistry,
3 Department of Biochemistry, Stanford University, Stanford, CA 94305-5025, USA.
4 Department of Chemistry, Box H, Brown University, Providence, RI 02912, USA.
*   Permanent address: Facultad de Ciencias Bioquimicas y Farmaceuticas, Departamento de Microbiologia, Suipacha 531, Rosario 2000, Argentina.

dagger    To whom correspondence should be addressed. E-mail: ck{at}chemeng.stanford.edu

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