Skip navigation
Skip navigation

Efficient backbone cyclization of linear peptides by a recombinant asparaginyl endopeptidase

Harris, Karen; Durek, Thomas; Kaas, Quentin; Poth, Aaron; Gilding, Edward; Conlan, Brendon; Saska, Ivana; Daly, Norelle; Van der Weerden, Nicole L.; Craik, David J; Anderson, Marilyn

Description

Cyclotides are diverse plant backbone cyclized peptidesthat have attracted interest as pharmaceutical scaffolds, but fundamentals of their biosynthetic origin remain elusive. Backbone cyclization is a key enzyme-mediated step of cyclotide biosynthesis and confers a measure of stability on the resultant cyclotide. Furthermore, cyclization would be desirable for engineered peptides. Here we report the identification of four asparaginyl endopeptidases (AEPs), proteases implicated in cyclization,...[Show more]

dc.contributor.authorHarris, Karen
dc.contributor.authorDurek, Thomas
dc.contributor.authorKaas, Quentin
dc.contributor.authorPoth, Aaron
dc.contributor.authorGilding, Edward
dc.contributor.authorConlan, Brendon
dc.contributor.authorSaska, Ivana
dc.contributor.authorDaly, Norelle
dc.contributor.authorVan der Weerden, Nicole L.
dc.contributor.authorCraik, David J
dc.contributor.authorAnderson, Marilyn
dc.date.accessioned2018-11-29T22:56:32Z
dc.date.available2018-11-29T22:56:32Z
dc.identifier.issn2041-1723
dc.identifier.urihttp://hdl.handle.net/1885/153553
dc.description.abstractCyclotides are diverse plant backbone cyclized peptidesthat have attracted interest as pharmaceutical scaffolds, but fundamentals of their biosynthetic origin remain elusive. Backbone cyclization is a key enzyme-mediated step of cyclotide biosynthesis and confers a measure of stability on the resultant cyclotide. Furthermore, cyclization would be desirable for engineered peptides. Here we report the identification of four asparaginyl endopeptidases (AEPs), proteases implicated in cyclization, from the cyclotide-producing plant Oldenlandia affinis. We recombinantly express OaAEP1b and find it functions preferably as a cyclase by coupling C-terminal cleavage of propeptide substrates with backbone cyclization. Interestingly, OaAEP1b cannot cleave at the N-terminal site of O. affinis cyclotide precursors, implicating additional proteases in cyclotide biosynthesis. Finally, we demonstrate the broad utility of this enzyme by cyclization of peptides unrelated to cyclotides. We propose that recombinant OaAEP1b is a powerful tool for use in peptide engineering applications where increased stability of peptide products is desired.
dc.format.mimetypeapplication/pdf
dc.publisherMacmillan Publishers Ltd
dc.rightsPlease request for Daly to be added as an internal ARIES author
dc.rightsNorelle L Daly does not belong to PSD therefore she is not internal author for PSD.
dc.sourceNature Communications
dc.titleEfficient backbone cyclization of linear peptides by a recombinant asparaginyl endopeptidase
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume6
dc.date.issued2015
local.identifier.absfor060199 - Biochemistry and Cell Biology not elsewhere classified
local.identifier.ariespublicationU3488905xPUB8497
local.type.statusPublished Version
local.contributor.affiliationHarris, Karen, La Trobe University
local.contributor.affiliationDurek, Thomas, The University of Queensland
local.contributor.affiliationKaas, Quentin, The University of Queensland
local.contributor.affiliationPoth, Aaron, The University of Queensland
local.contributor.affiliationGilding, Edward, The University of Queensland
local.contributor.affiliationConlan, Brendon, College of Science, ANU
local.contributor.affiliationSaska, Ivana, The University of Queensland
local.contributor.affiliationDaly, Norelle, The University of Queensland
local.contributor.affiliationVan der Weerden, Nicole L., La Trobe University
local.contributor.affiliationCraik, David J, University of Queensland
local.contributor.affiliationAnderson, Marilyn, La Trobe University
local.bibliographicCitation.issue10199
local.bibliographicCitation.startpage10199
local.bibliographicCitation.lastpage10199
local.identifier.doi10.1038/ncomms10199
local.identifier.absseo970106 - Expanding Knowledge in the Biological Sciences
dc.date.updated2018-11-29T08:12:54Z
local.identifier.scopusID2-s2.0-84951824827
local.identifier.thomsonID000367580600001
dcterms.accessRightsOpen Access
CollectionsANU Research Publications

Download

File Description SizeFormat Image
01_Harris_Efficient_backbone_cyclization_2015.pdf1.31 MBAdobe PDFThumbnail


Items in Open Research are protected by copyright, with all rights reserved, unless otherwise indicated.

Updated:  17 November 2022/ Responsible Officer:  University Librarian/ Page Contact:  Library Systems & Web Coordinator