Abstract
More than 100 cyclic peptides harboring heterocyclized residues are known from marine ascidians, sponges and different genera of cyanobacteria. Here, we report an assembly line responsible for the biosynthesis of these diverse peptides, now called cyanobactins, both in symbiotic and free-living cyanobacteria. By comparing five new cyanobactin biosynthetic clusters, we produced the prenylated antitumor preclinical candidate trunkamide in Escherichia coli culture using genetic engineering.
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Acknowledgements
This work was supported by grants from the US National Institutes of Health (GM071425) and the National Science Foundation (EF-0412226). We thank C. Ireland (University of Utah), the University of the South Pacific, the Solomon Islands and the Republic of the Fiji Islands for providing opportunities to collect marine animal samples. S. Meo (University of the South Pacific) aided with the collection of L. patella in Fiji. S. Carmeli (Tel-Aviv University) provided the N. spongiaeforme culture. J.G. Muller and T. Bugni (University of Utah) helped with mass spectrometry experiments. A. Bird and D. Winge (University of Utah) helped with yeast recombination. C. Ireland provided ascidian photos.
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M.S.D. performed all experiments and wrote the manuscript; J.R. did most of the sequencing and helped in editing the manuscript; E.W.S. did the original collection and processing of the marine samples, directed the project and helped write and edit the manuscript.
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E.W.S. is an inventor on a patent application at the University of Utah for the practical application of cyclic peptide library synthesis. Some of the claims are supported by this work.
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Donia, M., Ravel, J. & Schmidt, E. A global assembly line for cyanobactins. Nat Chem Biol 4, 341–343 (2008). https://doi.org/10.1038/nchembio.84
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DOI: https://doi.org/10.1038/nchembio.84
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