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

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