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Angew Chem Int Ed Engl. 2012 Jul 16;51(29):7181-4. doi: 10.1002/anie.201202043. Epub 2012 Jun 18.

Introduction of a non-natural amino acid into a nonribosomal peptide antibiotic by modification of adenylation domain specificity.

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1
School of Chemistry & Manchester Interdisciplinary Biocentre, The University of Manchester, 131 Princess Street, Manchester M1 7DN, UK.

Abstract

Calcium-dependent antibiotics (CDA) are cyclic lipopeptides assembled by nonribosomal peptide synthetase (NRPS) enzymes. Active site modification of the 3-methyl glutamate activating adenylation (A) domain of the CDA NRPS enables the incorporation of synthetic 3-methyl glutamine into CDA. This provides the first example of how A-domains can be engineered to introduce synthetic "non-natural" amino acids into nonribosomal peptides.

PMID:
22711659
DOI:
10.1002/anie.201202043
[Indexed for MEDLINE]
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