Introduction of a non-natural amino acid into a nonribosomal peptide antibiotic by modification of adenylation domain specificity.
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.
School of Chemistry & Manchester Interdisciplinary Biocentre, The University of Manchester, 131 Princess Street, Manchester M1 7DN, UK.
Jenny
J
Thirlway
Richard
R
Lewis
Laura
L
Nunns
Majid
M
Al Nakeeb
Matthew
M
Styles
Anna-Winona
AW
Struck
Colin P
CP
Smith
Jason
J
Micklefield
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D005973:Glutamine / Q000031:analogs & derivatives*; D055666:Lipopeptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D010453:Peptide Synthases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D048372:Streptomyces coelicolor / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity
D000900:Anti-Bacterial Agents; D055666:Lipopeptides; D010456:Peptides, Cyclic; D005973:Glutamine; D010453:Peptide Synthases; D002118:Calcium