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; David P Fewer; Wael E. Houssen

doi:10.1039/C7CC05913B

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

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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 language	English
Pages (from-to)	10656-10659
Number of pages	4
Journal	Chemical Communications
Volume	53
Issue number	77
Early online date	11 Sep 2017
DOIs	https://doi.org/10.1039/C7CC05913B
Publication status	Published - 4 Oct 2017

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10.1039/C7CC05913BLicence: CC BY

Cyclic peptide production using a macrocyclase with enhanced substrate promiscuity and relaxed recognition determinants
https://creativecommons.org/licenses/by/4.0/
Final published version, 1.53 MBLicence: CC BY

Wael E Houssen
- School of Medicine, Medical Sciences & Nutrition, Medical Sciences - Reader
- Institute of Medical Sciences
Person: Academic

Aberdeen Proteomics
David Stead (Manager)
Medical Sciences
Research Facilities: Facility

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Alexandru-Crivac, C. N., Umeobika, C., Leikoski, N., Jokela, J., Rickaby, K. A., Grilo, A. M., Sjö, P., Plowright, A. T., Idress, M., Siebs, E., Nneoyi-Egbe, A., Wahlsten, M., Sivonen, K., Jaspars, M., Trembleau, L., Fewer, D. P., & Houssen , W. E. (2017). Cyclic peptide production using a macrocyclase with enhanced substrate promiscuity and relaxed recognition determinants. Chemical Communications, 53(77), 10656-10659. https://doi.org/10.1039/C7CC05913B

Alexandru-Crivac, CN, Umeobika, C, Leikoski, N, Jokela, J, Rickaby, KA, Grilo, AM, Sjö, P, Plowright, AT, Idress, M, Siebs, E, Nneoyi-Egbe, A, Wahlsten, M, Sivonen, K, Jaspars, M , Trembleau, L, Fewer, DP & Houssen , WE 2017, 'Cyclic peptide production using a macrocyclase with enhanced substrate promiscuity and relaxed recognition determinants', Chemical Communications, vol. 53, no. 77, pp. 10656-10659. https://doi.org/10.1039/C7CC05913B

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title = "Cyclic peptide production using a macrocyclase with enhanced substrate promiscuity and relaxed recognition determinants",

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.",

author = "Alexandru-Crivac, {Cristina N.} and Christian Umeobika and Niina Leikoski and Jouni Jokela and Rickaby, {Kirstie A.} and Grilo, {Andr{\'e} M.} and Peter Sj{\"o} and Plowright, {Alleyn T.} and Mohannad Idress and Eike Siebs and Ada Nneoyi-Egbe and Matti Wahlsten and Kaarina Sivonen and Marcel Jaspars and Laurent Trembleau and Fewer, {David P} and Houssen, {Wael E.}",

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 ",

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doi = "10.1039/C7CC05913B",

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T1 - Cyclic peptide production using a macrocyclase with enhanced substrate promiscuity and relaxed recognition determinants

AU - Alexandru-Crivac, Cristina N.

AU - Umeobika, Christian

AU - Leikoski, Niina

AU - Jokela, Jouni

AU - Rickaby, Kirstie A.

AU - Grilo, André M.

AU - Sjö, Peter

AU - Plowright, Alleyn T.

AU - Idress, Mohannad

AU - Siebs, Eike

AU - Nneoyi-Egbe, Ada

AU - Wahlsten, Matti

AU - Sivonen, Kaarina

AU - Jaspars, Marcel

AU - Trembleau, Laurent

AU - Fewer, David P

AU - Houssen , Wael E.

N1 - 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

PY - 2017/10/4

Y1 - 2017/10/4

N2 - 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.

AB - 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.

U2 - 10.1039/C7CC05913B

DO - 10.1039/C7CC05913B

M3 - Article

VL - 53

SP - 10656

EP - 10659

JO - Chemical Communications

JF - Chemical Communications

SN - 1359-7345

IS - 77

ER -

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

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