Metabolic and evolutionary origin of actin-binding polyketides from diverse organisms

Reiko Ueoka, Agustinus R. Uria, Silke Reiter, Tetsushi Mori, Petra Karbaum, Eike E. Peters, Eric J N Helfrich, Brandon I. Morinaka, Muriel Gugger, Haruko Takeyama, Shigeki Matsunaga, Jörn Piel

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    58 Citations (Scopus)


    Actin-targeting macrolides comprise a large, structurally diverse group of cytotoxins isolated from remarkably dissimilar micro- and macroorganisms. In spite of their disparate origins and structures, many of these compounds bind actin at the same site and exhibit structural relationships reminiscent of modular, combinatorial drug libraries. Here we investigate biosynthesis and evolution of three compound groups: misakinolides, scytophycin-type compounds and luminaolides. For misakinolides from the sponge Theonella swinhoei WA, our data suggest production by an uncultivated 'Entotheonella' symbiont, further supporting the relevance of these bacteria as sources of bioactive polyketides and peptides in sponges. Insights into misakinolide biosynthesis permitted targeted genome mining for other members, providing a cyanobacterial luminaolide producer as the first cultivated source for this dimeric compound family. The data indicate that this polyketide family is bacteria-derived and that the unusual macrolide diversity is the result of combinatorial pathway modularity for some compounds and of convergent evolution for others.

    Original languageEnglish
    Pages (from-to)705-712
    Number of pages8
    JournalNature Chemical Biology
    Issue number9
    Publication statusPublished - 2015 Sep 20

    ASJC Scopus subject areas

    • Cell Biology
    • Molecular Biology

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    Ueoka, R., Uria, A. R., Reiter, S., Mori, T., Karbaum, P., Peters, E. E., Helfrich, E. J. N., Morinaka, B. I., Gugger, M., Takeyama, H., Matsunaga, S., & Piel, J. (2015). Metabolic and evolutionary origin of actin-binding polyketides from diverse organisms. Nature Chemical Biology, 11(9), 705-712.