Gene-guided discovery and ribosomal biosynthesis of anticancer moroidin peptides

<p>Moroidin is a bicyclic plant octapeptide with tryptophan side-chain crosslinks, originally isolated as a pain-causing agent from Australian stinging tree <em>Dendrocnide moroides</em>. Moroidin and its analog celogentin C, derived from <em>Celosia argentea</em>, are inhibitors of tubulin polymerization and, thus, lead structures for cancer therapy. However, low isolation yields from source plants and challenging organic synthesis hinder moroidin-based drug development. Here, we present biosynthesis as an alternative route to moroidin-type bicyclic peptides and report that they are ribosomally synthesized and posttranslationally modified peptides (RiPPs) derived from BURP-domain peptide cyclases in plants.</p> <p>This submission includes the 793 plant&nbsp;transcriptomes from the 1kp databases [1]&nbsp;of Table S2 which were assembled de novo by rnaSPAdes [2,3] and searched for moroidin peptide cyclases.</p> <ol> <li>Yan, Z., Carpenter, E.J., Wickett, N.J., Mirarab, S., Nguyen, N., Warnow, T., Ayyampalayam, S., Barker, M. and Burleigh, J.G., 2014. Data access for the 1,000 Plants (1KP) project.&nbsp;<em>Gigascience</em>,&nbsp;<em>3</em>(1), pp.2047-217X.</li> <li>Bankevich, A., Nurk, S., Antipov, D., Gurevich, A.A., Dvorkin, M., Kulikov, A.S., Lesin, V.M., Nikolenko, S.I., Pham, S., Prjibelski, A.D. and Pyshkin, A.V., 2012. SPAdes: a new genome assembly algorithm and its applications to single-cell sequencing.&nbsp;<em>Journal of computational biology</em>,&nbsp;<em>19</em>(5), pp.455-477.</li> <li>Bushmanova, E., Antipov, D., Lapidus, A. and Prjibelski, A.D., 2019. rnaSPAdes: a de novo transcriptome assembler and its application to RNA-Seq data.&nbsp;<em>GigaScience</em>,&nbsp;<em>8</em>(9), p.giz100.</li> </ol> <p>&nbsp;</p>