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dc.contributor.authorLudewig, Hannes
dc.contributor.authorCzekster, Clarissa M.
dc.contributor.authorOueis, Emilia
dc.contributor.authorMunday, Elizabeth S.
dc.contributor.authorArshad, Mohammed
dc.contributor.authorSynowsky, Silvia Anna
dc.contributor.authorBent, Andrew F.
dc.contributor.authorNaismith, James H.
dc.date.accessioned2019-01-29T00:34:08Z
dc.date.available2019-01-29T00:34:08Z
dc.date.issued2018-03-16
dc.identifier.citationLudewig , H , Czekster , C M , Oueis , E , Munday , E S , Arshad , M , Synowsky , S A , Bent , A F & Naismith , J H 2018 , ' Characterization of the fast and promiscuous macrocyclase from plant PCY1 enables the use of simple substrates ' , ACS Chemical Biology , vol. 13 , no. 3 , pp. 801–811 . https://doi.org/10.1021/acschembio.8b00050en
dc.identifier.issn1554-8929
dc.identifier.otherPURE: 252533619
dc.identifier.otherPURE UUID: ac3df20b-b907-44b8-988c-65066628949b
dc.identifier.otherScopus: 85044096395
dc.identifier.otherORCID: /0000-0002-7163-4057/work/59222326
dc.identifier.otherWOS: 000428003000038
dc.identifier.urihttp://hdl.handle.net/10023/16948
dc.descriptionH.L. is funded by the George and Stella Lee Scholarship and EPSRC. This project was funded by the European Research Council project 339367 NCB-TNT and by the BBSRC (J.H.N.). E.S.M. and M.A. are funded by EPSRC. S.A.S. is funded by BSRC mass spec facility.en
dc.description.abstractCyclic ribosomally derived peptides possess diverse bioactivities and are currently of major interest in drug development. However, it can be chemically challenging to synthesize these molecules, hindering the diversification and testing of cyclic peptide leads. Enzymes used in vitro offer a solution to this; however peptide macrocyclization remains the bottleneck. PCY1, involved in the biosynthesis of plant orbitides, belongs to the class of prolyl oligopeptidases and natively displays substrate promiscuity. PCY1 is a promising candidate for in vitro utilization, but its substrates require an 11 to 16 residue C-terminal recognition tail. We have characterized PCY1 both kinetically and structurally with multiple substrate complexes revealing the molecular basis of recognition and catalysis. Using these insights, we have identified a three residue C-terminal extension that replaces the natural recognition tail permitting PCY1 to operate on synthetic substrates. We demonstrate that PCY1 can macrocyclize a variety of substrates with this short tail, including unnatural amino acids and nonamino acids, highlighting PCY1’s potential in biocatalysis.
dc.language.isoeng
dc.relation.ispartofACS Chemical Biologyen
dc.rights© 2018, American Chemical Society. This work has been made available online in accordance with the publisher’s policies. This is the author created, accepted version manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at https://doi.org/10.1021/acschembio.8b00050en
dc.subjectQD Chemistryen
dc.subjectQH301 Biologyen
dc.subjectDASen
dc.subject.lccQDen
dc.subject.lccQH301en
dc.titleCharacterization of the fast and promiscuous macrocyclase from plant PCY1 enables the use of simple substratesen
dc.typeJournal articleen
dc.description.versionPostprinten
dc.contributor.institutionUniversity of St Andrews.School of Chemistryen
dc.contributor.institutionUniversity of St Andrews.School of Biologyen
dc.contributor.institutionUniversity of St Andrews.EaSTCHEMen
dc.contributor.institutionUniversity of St Andrews.Biomedical Sciences Research Complexen
dc.identifier.doihttps://doi.org/10.1021/acschembio.8b00050
dc.description.statusPeer revieweden
dc.date.embargoedUntil2019-01-29


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