AI Article Synopsis
- Tripropeptin C is a cyclic lipopeptide that effectively fights against methicillin-resistant Staphylococcus aureus in mice.
- Researchers replaced proline residues in tripropeptin C with pipecolic acid to explore its impact on antibacterial activity.
- The modified analog, tripropeptin Cpip, displayed significantly weaker efficacy against Gram-positive bacteria, indicating that the original proline structure is crucial for the compound's antibacterial potency.
Article Abstract
Tripropeptin C, a non-ribosomal cyclic lipopeptide containing three proline residues, exhibits excellent efficacy in the mouse-methicillin-resistant Staphylococcus aureus septicemia model. Since tripropeptins contain L-prolyl-D-proline and, as a result, are known to form a hairpin structure in proteins, it was of interest to determine whether this substructure contributes to their antibacterial activity. In this study, prolines in tripropeptin C were replaced with pipecolic acid(s) using precursor-directed biosynthesis. Only a new tripropeptin analog, tripropeptin Cpip, which has one L-pipecolic acid in place of L-proline, was isolated. The in vitro antimicrobial activity of the new analog was approximately two to four times weaker activity against Gram-positive bacteria, including drug-resistant species, compared with that of tripropeptin C. These results suggest that the L-prolyl-D-proline substructure plays an important role in the observed potency of tripropeptins.
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| http://dx.doi.org/10.1038/s41429-024-00703-9 | DOI Listing |
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