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Cell-free synthesis of polyketides by recombinant erythromycin polyketide synthases

Nature volume 378, pages 263266 (16 November 1995) | Download Citation

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Abstract

MODULAR polyketide synthases (PKSs) are complex multi-enzyme proteins that catalyse the bacterial biosynthesis of many pharma-ceutically useful polyketides. The PKSs are organized into a series of modules, each containing the active catalytic sites required for one step in the synthesis process1–4. Here we report a method for cell-free enzymatic synthesis of 6-deoxyerythronolide B (6-dEB), the parent molecule of the antibiotic erythromycin A, using recombinant 6-deoxyerythronolide B synthase (DEBS), a modular PKS with at least 28 distinct active sites. We have also synthesized in vitro a triketide lactone by using a truncated mutant of DEBS. The availability of such cell-free synthetic routes will allow direct investigation of the structural and mechanistic basis for the unusual combination of high substrate specificity5–10 and tolerance to genetic reprogramming2,11–15 found in this enzyme family.

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Affiliations

  1. Department of Chemical Engineering, Stanford University, Stanford, California 94305-5025, USA

    • Rembert Pieper
    •  & C. Khosla
  2. Department of Chemistry, Brown University, Box H, Providence, Rhode Island 02912, USA

    • Guanglin Luo
    •  & David E. Cane

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https://doi.org/10.1038/378263a0

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