Gene-guided discovery and ribosomal biosynthesis of anticancer moroidin peptides

Moroidin is a bicyclic plant octapeptide with tryptophan side-chain crosslinks, originally isolated as a pain-causing agent from Australian stinging tree Dendrocnide moroides. Moroidin and its analog celogentin C, derived from Celosia argentea, 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.

This submission includes the 793 plant transcriptomes from the 1kp databases [1] of Table S2 which were assembled de novo by rnaSPAdes [2,3] and searched for moroidin peptide cyclases.

1. 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. Gigascience, 3(1), pp.2047-217X.
2. 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. Journal of computational biology, 19(5), pp.455-477.
3. Bushmanova, E., Antipov, D., Lapidus, A. and Prjibelski, A.D., 2019. rnaSPAdes: a de novo transcriptome assembler and its application to RNA-Seq data. GigaScience, 8(9), p.giz100.