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An unusually large multifunctional polypeptide in the erythromycin-producing polyketide synthase of Saccharopolyspora erythraea

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Abstract

ERYTHROMYCIN A, a clinically important polyketide antibiotic, is produced by the Gram-positive bacterium Saccharopolyspora erythraea.. In an arrangement that seems to be generally true of antibiotic biosynthetic genes in Streptomyces and related bacteria like S. erythraea1, the ery genes encoding the biosynthetic pathway to erythromvein are clustered around the gene (ermE) that confers self-resistance on S. erythraea2–6. The aglycone core of erythro-mycin A is derived from one propionyl-CoA and six methylmalonyl-CoA units, which are incorporated head-to-tail7–10 into the growing polyketide chain, in a process similar to that of fatty-acid biosynthesis1, to generate a macrolide intermediate, 6-deoxyeryth-ronolide B10. 6-Deoxyerythronolide B is converted into erythro-mycin A through the action2–5,10 of specific hydroxylases, glycosyItransferases and a methyltransferase. We report here the analysis of about 10 kilobases of DNA from S. erythraea, cloned by chromosome 'walking' outwards from the erythromycin-resistance determinant ermE, and previously shown to be essential for erythromycin biosynthesis5,11. Partial sequencing of this region12 indicates that it encodes the synthase. Our results confirm this, and reveal a novel organization of the erythromycin-producing polyketide synthase, which provides further insight into the mechanism of chain assembly.

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Authors and Affiliations

  1. Department of Biochemistry, and Cambridge Centre for Molecular Recognition, University of Cambridge, Tennis Court Road, Cambridge, CB21QW, UK

    Jesus Cortes, Stephen F. Haydock, Gareth A. Roberts, Debra J. Bevitt & Peter F. Leadlay

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  1. Jesus Cortes
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  2. Stephen F. Haydock
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  3. Gareth A. Roberts
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  4. Debra J. Bevitt
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  5. Peter F. Leadlay
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Cortes, J., Haydock, S., Roberts, G. et al. An unusually large multifunctional polypeptide in the erythromycin-producing polyketide synthase of Saccharopolyspora erythraea. Nature 348, 176–178 (1990). https://doi.org/10.1038/348176a0

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