Bypassing the proline/thiazoline requirement of the macrocyclase PatG?

Chemical Communications Pub Date: 2017-11-01 DOI: 10.1039/C7CC06550G

Abstract

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.

Graphical abstract: Bypassing the proline/thiazoline requirement of the macrocyclase PatG
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