Cyclic peptide production using a macrocyclase with enhanced substrate promiscuity and relaxed recognition determinants

Cristina N. Alexandru-Crivac, Christian Umeobika, Niina Leikoski, Jouni Jokela, Kirstie A. Rickaby, André M. Grilo, Peter Sjö, Alleyn T. Plowright, Mohannad Idress, Eike Siebs, Ada Nneoyi-Egbe, Matti Wahlsten, Kaarina Sivonen, Marcel Jaspars, Laurent Trembleau* (Corresponding Author), David P Fewer, Wael E. Houssen * (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)
17 Downloads (Pure)

Abstract

Macrocyclic peptides have promising therapeutic potential but the scaling up of their chemical synthesis is challenging. The cyanobactin macrocyclase PatGmac is an efficient tool for production but is limited to substrates containing 6–11 amino acids and at least one thiazoline or proline. Here we report a new cyanobactin macrocyclase that can cyclize longer peptide substrates and those not containing proline/thiazoline and thus allows exploring a wider chemical diversity.
Original languageEnglish
Pages (from-to)10656-10659
Number of pages4
JournalChemical Communications
Volume53
Issue number77
Early online date11 Sept 2017
DOIs
Publication statusPublished - 4 Oct 2017

Bibliographical note

This project was supported by grants from the ERC (no. 339367, MJ), BBSRC IBCatalyst (no. BB/M028526/1, MJ, WEH), BBSRC FoF (no. BB/M013669/1, MJ, WEH), IBioIC Exemplar (no. 2014-2-4, MJ, WEH), an AstraZeneca studentship (MJ, WEH, LT, KR), the Academy of Finland (no. 259505, DPF) and the SULSA leaders award (WEH). The authors like to thank the Aberdeen Proteomics Facility and the Aberdeen School of Natural and Computing Sciences MS Facility for LCMS analysis.
Electronic supplementary information (ESI) available: Experimental section, Fig. S1–S60 and Tables S1–S3. See DOI: 10.1039/c7cc05913b

Fingerprint

Dive into the research topics of 'Cyclic peptide production using a macrocyclase with enhanced substrate promiscuity and relaxed recognition determinants'. Together they form a unique fingerprint.

Cite this