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The genetic origin of evolidine, the first cyclopeptide discovered in plants, and related orbitides
journal contributionposted on 2021-01-19, 02:35 authored by Mark F Fisher, Colton D Payne, Thaveshini Chetty, Darren M Crayn, Oliver BerkowitzOliver Berkowitz, James WhelanJames Whelan, K Johan Rosengren, Joshua S Mylne
© 2020 American Society for Biochemistry and Molecular Biology Inc.. All rights reserved. Cyclic peptides are reported to have antibacterial, antifungal, and other bioactivities. Orbitides are a class of cyclic peptides that are small, head-to-tail cyclized, composed of proteinogenic amino acids and lack disulfide bonds; they are also known in several genera of the plant family Rutaceae. Melicope xanthoxyloides is the Australian rain forest tree of the Rutaceae family in which evolidine, the first plant cyclic peptide, was discovered. Evolidine (cyclo-SFLPVNL) has subsequently been all but forgotten in the academic literature, so to redress this we used tandem MS and de novo transcriptomics to rediscover evolidine and decipher its biosynthetic origin from a short precursor just 48 residues in length. We also identified another six M. xanthoxyloides orbitides using the same techniques. These peptides have atypically diverse C termini consisting of residues not recognized by either of the known proteases plants use to macrocyclize peptides, suggesting new cyclizing enzymes await discovery. We examined the structure of two of the novel orbitides by NMR, finding one had a definable structure, whereas the other did not. Mining RNA-seq and whole genome sequencing data from other species of the Rutaceae family revealed that a large and diverse family of peptides is encoded by similar sequences across the family and demonstrates how powerful de novo transcriptomics can be at accelerating the discovery of new peptide families.
This work was supported by Australian Research Council Grants DP190102058 (to J. S. M. and K. J. R.) and CE140100008 (to J. W.). M. F. F. was supported by the Australian Research Training Program and a Bruce and Betty Green Postgraduate Research Scholarship.
JournalJournal of Biological Chemistry
Pagination12p. (p. 14510-14521)
PublisherAmerican Society for Biochemistry and Molecular Biology Inc.
Rights StatementThe Author reserves all moral rights over the deposited text and must be credited if any re-use occurs. Documents deposited in OPAL are the Open Access versions of outputs published elsewhere. Changes resulting from the publishing process may therefore not be reflected in this document. The final published version may be obtained via the publisher’s DOI. Please note that additional copyright and access restrictions may apply to the published version.
Science & TechnologyLife Sciences & BiomedicineBiochemistry & Molecular Biologycyclic peptidepeptide biosynthesisplant biochemistryplant molecular biologymass spectrometry (MS)orbitideRiPPRNA-seqde novo transcriptomicsNMR CHEMICAL-SHIFTSCYCLIC-PEPTIDESAUSTRALIAN RUTACEAEPROTEIN BACKBONEYUNNANIN-ABIOSYNTHESISCARYOPHYLLACEAECONFORMATIONSHEPTAPEPTIDEALKALOIDS