Content area
Full Text
The Journal of Antibiotics (2013) 66, 7378& 2013 Japan Antibiotics Research Association All rights reserved 0021-8820/13 http://www.nature.com/ja
Web End =www.nature.com/ja
Matteo Simone1,2,3, Paolo Monciardini3, Eleonora Gaspari4, Stefano Donadio1 and Sonia I Mafoli1
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, 7378; doi:http://dx.doi.org/10.1038/ja.2012.92
Web End =10.1038/ja.2012.92; published online 21 November 2012
Keywords: Actinoplanes; antibiotic; lantibiotics
INTRODUCTION
The lantibiotic NAI-107 (previously known as 107891 or microbisporicin), produced by Microbispora sp.,1 displays potent activity against most Gram-positive pathogens of medical importance2 and is effective in experimental models of infection.3 This compound was isolated after high-throughput screening (HTS) of ca. 120 000 microbial broth extracts through a program for identication of compounds active on bacterial cell wall. Unexpectedly, this assay system turned out to signicantly enrich for lantibiotics.4 We thus decided to further investigate the samples positive in that screening program and report here the isolation, structure elucidation and preliminary biological proling of a new lantibiotic, designated NAI-802.
Our proprietary Natural Products Library database contains information regarding strains, their growth conditions (media, growth temperatures and harvest times) and extracts (preparation procedure). It also reports data obtained with extracts in the differentHTS programs run at Biosearch Italia/Vicuron Pharmaceuticals in the 19962006 period. Overall, it covers about 70 000 strains, 160 000 extracts and over 20 HTS programs. Details of the screening project for identication of compounds active on bacterial cell wall have been described elsewhere.4 Briey, the program involved...