Efficient backbone cyclization of linear peptides by a recombinant asparaginyl endopeptidase
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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.author | Harris, Karen | |
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dc.contributor.author | Durek, Thomas | |
dc.contributor.author | Kaas, Quentin | |
dc.contributor.author | Poth, Aaron | |
dc.contributor.author | Gilding, Edward | |
dc.contributor.author | Conlan, Brendon | |
dc.contributor.author | Saska, Ivana | |
dc.contributor.author | Daly, Norelle | |
dc.contributor.author | Van der Weerden, Nicole L. | |
dc.contributor.author | Craik, David J | |
dc.contributor.author | Anderson, Marilyn | |
dc.date.accessioned | 2018-11-29T22:56:32Z | |
dc.date.available | 2018-11-29T22:56:32Z | |
dc.identifier.issn | 2041-1723 | |
dc.identifier.uri | http://hdl.handle.net/1885/153553 | |
dc.description.abstract | 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, 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.mimetype | application/pdf | |
dc.publisher | Macmillan Publishers Ltd | |
dc.rights | Please request for Daly to be added as an internal ARIES author | |
dc.rights | Norelle L Daly does not belong to PSD therefore she is not internal author for PSD. | |
dc.source | Nature Communications | |
dc.title | Efficient backbone cyclization of linear peptides by a recombinant asparaginyl endopeptidase | |
dc.type | Journal article | |
local.description.notes | Imported from ARIES | |
local.identifier.citationvolume | 6 | |
dc.date.issued | 2015 | |
local.identifier.absfor | 060199 - Biochemistry and Cell Biology not elsewhere classified | |
local.identifier.ariespublication | U3488905xPUB8497 | |
local.type.status | Published Version | |
local.contributor.affiliation | Harris, Karen, La Trobe University | |
local.contributor.affiliation | Durek, Thomas, The University of Queensland | |
local.contributor.affiliation | Kaas, Quentin, The University of Queensland | |
local.contributor.affiliation | Poth, Aaron, The University of Queensland | |
local.contributor.affiliation | Gilding, Edward, The University of Queensland | |
local.contributor.affiliation | Conlan, Brendon, College of Science, ANU | |
local.contributor.affiliation | Saska, Ivana, The University of Queensland | |
local.contributor.affiliation | Daly, Norelle, The University of Queensland | |
local.contributor.affiliation | Van der Weerden, Nicole L., La Trobe University | |
local.contributor.affiliation | Craik, David J, University of Queensland | |
local.contributor.affiliation | Anderson, Marilyn, La Trobe University | |
local.bibliographicCitation.issue | 10199 | |
local.bibliographicCitation.startpage | 10199 | |
local.bibliographicCitation.lastpage | 10199 | |
local.identifier.doi | 10.1038/ncomms10199 | |
local.identifier.absseo | 970106 - Expanding Knowledge in the Biological Sciences | |
dc.date.updated | 2018-11-29T08:12:54Z | |
local.identifier.scopusID | 2-s2.0-84951824827 | |
local.identifier.thomsonID | 000367580600001 | |
dcterms.accessRights | Open Access | |
Collections | ANU Research Publications |
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01_Harris_Efficient_backbone_cyclization_2015.pdf | 1.31 MB | Adobe PDF |
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