The genetic origin of evolidine, the first cyclopeptide discovered in plants, and related orbitides

Fisher, Mark F., Payne, Colton D., Chetty, Thaveshini, Crayn, Darren, Berkowitz, Oliver, Whelan, James, Rosengren, K. Johan, and Mylne, Joshua S. (2020) The genetic origin of evolidine, the first cyclopeptide discovered in plants, and related orbitides. Journal of Biological Chemistry, 295 (42). pp. 14510-14521.

PDF (Published Version) - Published Version
Available under License Creative Commons Attribution.

Download (1MB) | Preview
View at Publisher Website:


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.

Item ID: 66279
Item Type: Article (Research - C1)
ISSN: 1083-351X
Copyright Information: © 2020 Fisher et al. Published under exclusive license by The American Society for Biochemistry and Molecular Biology, Inc. This is an Open Access article under the CC BY license.
Funders: Australian Research Council (ARC), Australian Research Training Program, Bruce and Betty Green Postgraduate Research Scholarship
Projects and Grants: ARC DP190102058, ARC CE14010000
Date Deposited: 25 Feb 2021 00:05
FoR Codes: 31 BIOLOGICAL SCIENCES > 3108 Plant biology > 310802 Plant biochemistry @ 100%
SEO Codes: 28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280102 Expanding knowledge in the biological sciences @ 100%
Downloads: Total: 743
Last 12 Months: 16
More Statistics

Actions (Repository Staff Only)

Item Control Page Item Control Page