Mechanistically Distinct Nonribosomal Peptide Synthetases Assemble the Structurally Related Antibiotics Viomycin and Capreomycin

Authors

  • Dr. Elizabeth A. Felnagle,

    1. Department of Bacteriology, University of Wisconsin–Madison, 1550 Linden Drive, Madison, WI 53706 (USA)
    2. Microbiology Doctoral Training Program, University of Wisconsin–Madison, 1550 Linden Drive, Madison, WI 53706 (USA)
    3. Present address: Department of Chemical and Biomolecular Engineering, University of California, 420 Westwood Plaza, Los Angeles, CA 90095 (USA)
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  • Angela M. Podevels,

    1. Department of Bacteriology, University of Wisconsin–Madison, 1550 Linden Drive, Madison, WI 53706 (USA)
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  • John J. Barkei,

    1. Department of Bacteriology, University of Wisconsin–Madison, 1550 Linden Drive, Madison, WI 53706 (USA)
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  • Prof. Michael G. Thomas

    Corresponding author
    1. Department of Bacteriology, University of Wisconsin–Madison, 1550 Linden Drive, Madison, WI 53706 (USA)
    2. Microbiology Doctoral Training Program, University of Wisconsin–Madison, 1550 Linden Drive, Madison, WI 53706 (USA)
    • Department of Bacteriology, University of Wisconsin–Madison, 1550 Linden Drive, Madison, WI 53706 (USA)
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Abstract

original image

Tuberactinomycin biosynthesis: Viomycin and capreomycin are structurally related antituberculosis drugs. Analysis of the nonribosomal peptide synthetases that assemble these molecules determined that peptide assembly occurs by distinct mechanisms. These unexpected differences provide insights into how modifications to homologous nonribosomal peptide synthetases can result in structure diversification.

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