Journal
JOURNAL OF ANTIBIOTICS
Volume 66, Issue 2, Pages 73-78Publisher
JAPAN ANTIBIOTICS RESEARCH ASSOC
DOI: 10.1038/ja.2012.92
Keywords
Actinoplanes; antibiotic; lantibiotics
Funding
- Italian MIUR
- Regione Lombardia
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Lantibiotics are biologically active peptides produced by Gram-positive bacteria. Starting from fermentation broth extracts preselected from a high-throughput screening program for discovering cell-wall inhibitors, we successfully isolated a new lantibiotic produced by Actinoplanes sp., designated as NAI-802. MS and NMR analysis together with explorative chemistry established that NAI-802 consists of 21 amino acids, 19 of which are identical to those present in the class II lantibiotic actagardine. Interestingly, NAI-802 carries one extra alanine and one extra arginine at the N- and C-termini, respectively. As expected from the overall higher positive charge, NAI-802 was slightly more active than actagardine against staphylococci and streptococci. Further improvement of its antibacterial activity was achieved by adding one additional positive charge through conversion of the C-terminal carboxylate into the corresponding basic amide. NAI-802 thus represents a novel promising candidate for treating Gram-positive infections caused by multidrug-resistant pathogens. The Journal of Antibiotics (2013) 66, 73-78; doi:10.1038/ja.2012.92; published online 21 November 2012
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