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Monitoring the Assembly of a Secreted Bacterial Virulence Factor Using Site-specific Crosslinking
Published on: December 17, 2013
P450 Disruption Reveals Unforeseen Biaryl Cross-Link Chemistry in Glycopeptide Antibiotics
Jiawei Cao1,2, Xingkun Li2,3,4, Liyuan Zhang2,5
1School of Chemistry and Chemical Engineering, Linyi University, Linyi, Shandong 276000, China.
Abstract:
Glycopeptide antibiotics (GPAs) are the drug of choice for treating multidrug-resistant Gram-positive infections. GPAs possess a unique aromatic amino-acid-rich scaffold interconnected by a diverse set of biaryl cross-links, contributing to their rigid 3D structures for specific target binding on the cell wall. Disruption of the P450 genes responsible for biaryl linkage formation from the biosynthetic gene cluster of varsomycin identified a never-before-seen macrocyclic ring system in GPA, which greatly expands the chemical space of GPAs.
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