An Efficient Method for the In Vitro Production of Azol(in)e‐Based Cyclic Peptides1. Issue 51 (21st October 2014)

• Record Type: Journal Article
• Authors: Houssen, Wael E.; Bent, Andrew F.; McEwan, Andrew R.; Pieiller, Nathalie; Tabudravu, Jioji; Koehnke, Jesko; Mann, Greg; Adaba, Rosemary I.; Thomas, Louise; Hawas, Usama W.; Liu, Huanting; Schwarz‐Linek, Ulrich; Smith, Margaret C. M.; Naismith, James H.; Jaspars, Marcel
• Is Part Of: Angewandte Chemie international edition. Volume 53:Issue 51(2014)
• Page Start: 14171
• Page End: 14174
• Publication Date: 2014-10-21
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201408082
• Languages: English
• ISSNs: 1433-7851

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>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.</p> </abstract>