Efficient backbone cyclization of linear peptides by a recombinant asparaginyl endopeptidase

Harris, Karen S., Durek, Thomas, Kaas, Quentin, Poth, Aaron G., Gilding, Edward K., Conlan, Brendon F., Saska, Ivana, Daly, Norelle L., Van Der Weerden, Nicole L., Craik, David J. and Anderson, Marilyn A. (2015) Efficient backbone cyclization of linear peptides by a recombinant asparaginyl endopeptidase. Nature Communications, 6 10199: . doi:10.1038/ncomms10199

Author Harris, Karen S.
Durek, Thomas
Kaas, Quentin
Poth, Aaron G.
Gilding, Edward K.
Conlan, Brendon F.
Saska, Ivana
Daly, Norelle L.
Van Der Weerden, Nicole L.
Craik, David J.
Anderson, Marilyn A.
Title Efficient backbone cyclization of linear peptides by a recombinant asparaginyl endopeptidase
Journal name Nature Communications   Check publisher's open access policy
ISSN 2041-1723
Publication date 2015-12-18
Year available 2015
Sub-type Article (original research)
DOI 10.1038/ncomms10199
Open Access Status DOI
Volume 6
Issue 10199
Total pages 10
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Formatted abstract
Cyclotides are diverse plant backbone cyclized peptides that 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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 25 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 26 times in Scopus Article | Citations
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