An efficient method for the in vitro production of Azol(in)e-based cyclic peptides

W.E. Houssen; A.F. Bent; A.R. McEwan; N. Pieiller; J. Tabudravu; J. Koehnke; G. Mann; R.I. Adaba; L. Thomas; U.W. Hawas; H. Liu; U. Schwarz-Linek; M.C.M. Smith; J.H. Naismith; M. Jaspars

doi:10.1002/anie.201408082

An efficient method for the in vitro production of Azol(in)e-based cyclic peptides

W.E. Houssen, A.F. Bent, A.R. McEwan, N. Pieiller, J. Tabudravu, J. Koehnke, G. Mann, R.I. Adaba, L. Thomas, U.W. Hawas, H. Liu, U. Schwarz-Linek, M.C.M. Smith, J.H. Naismith, M. Jaspars

Research output: Contribution to journal › Article › peer-review

Abstract

Heterocycle-containing cyclic peptides are promising scaffolds for the pharmaceutical industry but their chemical synthesis is very challenging. A new universal method has been devised to prepare these compounds by using a set of engineered marine-derived enzymes and substrates obtained from a family of ribosomally produced and post-translationally modified peptides called the cyanobactins. The substrate precursor peptide is engineered to have a non-native protease cleavage site that can be rapidly cleaved. The other enzymes used are heterocyclases that convert Cys or Cys/Ser/Thr into their corresponding azolines. A macrocycle is formed using a macrocyclase enzyme, followed by oxidation of the azolines to azoles with a specific oxidase. The work is exemplified by the production of 17 macrocycles containing 6-9 residues representing 11 out of the 20 canonical amino acids.

Original language	English
Pages (from-to)	14171-14174
Number of pages	4
Journal	Angewandte Chemie International Edition
Volume	53
Issue number	51
Early online date	21 Oct 2014
DOIs	https://doi.org/10.1002/anie.201408082
Publication status	Published - 15 Dec 2014

Keywords

Cyanobactins
Cyclic peptides
Biosynthesis
Patellamides
Ribosomal peptides

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1002/anie.201408082

Naismith_2014_ACIE_Efficient
© 2014 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited (http://creativecommons.org/licenses/by/4.0/)
Final published version, 456 KB

Cite this

Houssen, W. E., Bent, A. F., McEwan, A. R., Pieiller, N., Tabudravu, J., Koehnke, J., Mann, G., Adaba, R. I., Thomas, L., Hawas, U. W., Liu, H., Schwarz-Linek, U., Smith, M. C. M., Naismith, J. H., & Jaspars, M. (2014). An efficient method for the in vitro production of Azol(in)e-based cyclic peptides. Angewandte Chemie International Edition, 53(51), 14171-14174. https://doi.org/10.1002/anie.201408082

@article{d27dd74ba3324f7a8dde97e16ac1391c,

title = "An efficient method for the in vitro production of Azol(in)e-based cyclic peptides",

abstract = "Heterocycle-containing cyclic peptides are promising scaffolds for the pharmaceutical industry but their chemical synthesis is very challenging. A new universal method has been devised to prepare these compounds by using a set of engineered marine-derived enzymes and substrates obtained from a family of ribosomally produced and post-translationally modified peptides called the cyanobactins. The substrate precursor peptide is engineered to have a non-native protease cleavage site that can be rapidly cleaved. The other enzymes used are heterocyclases that convert Cys or Cys/Ser/Thr into their corresponding azolines. A macrocycle is formed using a macrocyclase enzyme, followed by oxidation of the azolines to azoles with a specific oxidase. The work is exemplified by the production of 17 macrocycles containing 6-9 residues representing 11 out of the 20 canonical amino acids.",

keywords = "Cyanobactins, Cyclic peptides, Biosynthesis, Patellamides, Ribosomal peptides",

author = "W.E. Houssen and A.F. Bent and A.R. McEwan and N. Pieiller and J. Tabudravu and J. Koehnke and G. Mann and R.I. Adaba and L. Thomas and U.W. Hawas and H. Liu and U. Schwarz-Linek and M.C.M. Smith and J.H. Naismith and M. Jaspars",

note = "This paper was funded by: Funded Access, Leverhulme Trust. Grant Number: RPG-2012-504, TSB. Grant Number: 131181, ERC. Grant Number: 339367, and BBSRC. Grant Number: BB/K015508/1",

year = "2014",

month = dec,

day = "15",

doi = "10.1002/anie.201408082",

language = "English",

volume = "53",

pages = "14171--14174",

journal = "Angewandte Chemie International Edition",

issn = "1433-7851",

publisher = "John Wiley & Sons, Ltd",

number = "51",

}

Houssen, WE, Bent, AF, McEwan, AR, Pieiller, N, Tabudravu, J, Koehnke, J, Mann, G, Adaba, RI, Thomas, L, Hawas, UW, Liu, H, Schwarz-Linek, U, Smith, MCM, Naismith, JH & Jaspars, M 2014, 'An efficient method for the in vitro production of Azol(in)e-based cyclic peptides', Angewandte Chemie International Edition, vol. 53, no. 51, pp. 14171-14174. https://doi.org/10.1002/anie.201408082

TY - JOUR

T1 - An efficient method for the in vitro production of Azol(in)e-based cyclic peptides

AU - Houssen, W.E.

AU - Bent, A.F.

AU - McEwan, A.R.

AU - Pieiller, N.

AU - Tabudravu, J.

AU - Koehnke, J.

AU - Mann, G.

AU - Adaba, R.I.

AU - Thomas, L.

AU - Hawas, U.W.

AU - Liu, H.

AU - Schwarz-Linek, U.

AU - Smith, M.C.M.

AU - Naismith, J.H.

AU - Jaspars, M.

N1 - This paper was funded by: Funded Access, Leverhulme Trust. Grant Number: RPG-2012-504, TSB. Grant Number: 131181, ERC. Grant Number: 339367, and BBSRC. Grant Number: BB/K015508/1

PY - 2014/12/15

Y1 - 2014/12/15

N2 - Heterocycle-containing cyclic peptides are promising scaffolds for the pharmaceutical industry but their chemical synthesis is very challenging. A new universal method has been devised to prepare these compounds by using a set of engineered marine-derived enzymes and substrates obtained from a family of ribosomally produced and post-translationally modified peptides called the cyanobactins. The substrate precursor peptide is engineered to have a non-native protease cleavage site that can be rapidly cleaved. The other enzymes used are heterocyclases that convert Cys or Cys/Ser/Thr into their corresponding azolines. A macrocycle is formed using a macrocyclase enzyme, followed by oxidation of the azolines to azoles with a specific oxidase. The work is exemplified by the production of 17 macrocycles containing 6-9 residues representing 11 out of the 20 canonical amino acids.

AB - Heterocycle-containing cyclic peptides are promising scaffolds for the pharmaceutical industry but their chemical synthesis is very challenging. A new universal method has been devised to prepare these compounds by using a set of engineered marine-derived enzymes and substrates obtained from a family of ribosomally produced and post-translationally modified peptides called the cyanobactins. The substrate precursor peptide is engineered to have a non-native protease cleavage site that can be rapidly cleaved. The other enzymes used are heterocyclases that convert Cys or Cys/Ser/Thr into their corresponding azolines. A macrocycle is formed using a macrocyclase enzyme, followed by oxidation of the azolines to azoles with a specific oxidase. The work is exemplified by the production of 17 macrocycles containing 6-9 residues representing 11 out of the 20 canonical amino acids.

KW - Cyanobactins

KW - Cyclic peptides

KW - Biosynthesis

KW - Patellamides

KW - Ribosomal peptides

UR - http://onlinelibrary.wiley.com/doi/10.1002/anie.201408082/suppinfo

U2 - 10.1002/anie.201408082

DO - 10.1002/anie.201408082

M3 - Article

AN - SCOPUS:84917710839

SN - 1433-7851

VL - 53

SP - 14171

EP - 14174

JO - Angewandte Chemie International Edition

JF - Angewandte Chemie International Edition

IS - 51

ER -

An efficient method for the in vitro production of Azol(in)e-based cyclic peptides

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Exploring the mechanism: Exploring the mechanism and scope of the enzymatic formation of five membered ring

13TSB SynBio: 13TSB Synbio-Enhanced discovery and scalable synthesis of therapeutic cyclic peptides

Cite this

An efficient method for the in vitro production of Azol(in)e-based cyclic peptides

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Projects

Exploring the mechanism: Exploring the mechanism and scope of the enzymatic formation of five membered ring

13TSB SynBio: 13TSB Synbio-Enhanced discovery and scalable synthesis of therapeutic cyclic peptides

Cite this