Bypassing the proline/thiazoline requirement of the macrocyclase PatG† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c7cc06550g

Macrocyclisation of fully non-peptidic compounds and non-heterocycle containing macrocycles using the peptidic ligase PatGmac. Biocatalysis is a fast developing field in which an enzyme's natural capabilities are harnessed or engineered for synthetic chemistry. The enzyme PatG is an extremely p...

Full description

Saved in:
Bibliographic Details
Published in:Chemical communications (Cambridge, England) England), 2017-11, Vol.53 (91), p.12274-12277
Main Authors: Oueis, E., Stevenson, H., Jaspars, M., Westwood, N. J., Naismith, J. H.
Format: Article
Language:English
Subjects:
Chemistry
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Macrocyclisation of fully non-peptidic compounds and non-heterocycle containing macrocycles using the peptidic ligase PatGmac. Biocatalysis is a fast developing field in which an enzyme's natural capabilities are harnessed or engineered for synthetic chemistry. The enzyme PatG is an extremely promiscuous macrocyclase enzyme tolerating both non-natural amino acids and non-amino acids within the substrate. It does, however, require a proline or thiazoline at the C-terminal position of the core peptide which means the final product must contain this group. Here, we show guided by structural insight we have identified two synthetic routes, triazole and a double cysteine, that circumvent this requirement. With the triazole, we show PatGmac can macrocyclise substrates that do not contain any amino acids in the final product.
ISSN:1359-7345
1364-548X
DOI:10.1039/c7cc06550g