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Bypassing the proline/thiazoline requirement of the macrocyclase PatG.


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.

SUBMITTER: Oueis E 

PROVIDER: S-EPMC5708355 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Bypassing the proline/thiazoline requirement of the macrocyclase PatG.

Oueis E E   Stevenson H H   Jaspars M M   Westwood N J NJ   Naismith J H JH  

Chemical communications (Cambridge, England) 20171101 91


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 s  ...[more]

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