Abstract
With the increasing need of effective antibiotics against multi-drug resistant pathogens, lantibiotics are an attractive option of a new class of molecules. They are ribosomally synthetized and posttranslationally modified peptides possessing potent antimicrobial activity against aerobic and anaerobic Gram-positive pathogens, including those increasingly resistant to β-lactams and glycopeptides. Some of them (actagardine, mersacidin, planosporicin, and microbisporicin) inhibit cell wall biosynthesis in pathogens and their effect is not antagonized by vancomycin. Hereby, we apply an efficient strategy for lantibiotic screening to 240 members of a newly described genus of filamentous actinomycetes, named Actinoallomurus, that is considered a yet-poorly-exploited promising source for novel bioactive metabolites. By combining antimicrobial differential assay against Staphylococcus aureus and its L-form (also in the presence of a β-lactamase cocktail or Ac-Lys-D-alanyl-D-alanine tripeptide), with LC-UV-MS dereplication coupled with bioautography, a novel producer of the potent microbisporicin complex was rapidly identified. Under the commercial name of NAI-107, it is currently in late preclinical phase for the treatment of multi-dru...Continue Reading
References
May 1, 1976·The Journal of Antibiotics·V ArioliL G Silvestri
Mar 1, 1977·Antimicrobial Agents and Chemotherapy·S SommaF Parenti
May 15, 1997·European Journal of Biochemistry·H BrötzH G Sahl
Feb 4, 1998·Antimicrobial Agents and Chemotherapy·H BrötzH G Sahl
Nov 1, 1963·Journal of General Microbiology·R E WILLIAMS
Jan 11, 2005·Current Protein & Peptide Science·Paul D CotterR Paul Ross
Sep 16, 2006·Science·Hester E HasperEefjan Breukink
May 2, 2007·Biochemistry·Franca CastiglioneEnrico Selva
Oct 30, 2007·Cellular and Molecular Life Sciences : CMLS·J LubelskiO P Kuipers
Jan 25, 2008·Chemistry & Biology·Franca CastiglioneFrancesco Parenti
Jun 6, 2008·Current Opinion in Pharmacology·Richard H Baltz
Apr 21, 2009·Methods in Enzymology·Flavia Marinelli
Apr 21, 2009·Methods in Enzymology·Jesús CortésMichael J Dawson
Jul 2, 2009·International Journal of Systematic and Evolutionary Microbiology·Tomohiko TamuraKen-ichiro Suzuki
Jul 16, 2010·Proceedings of the National Academy of Sciences of the United States of America·Lucy C Foulston, Mervyn J Bibb
Oct 26, 2010·Trends in Biotechnology·Srdjan JoveticJohannes Tramper
Dec 2, 2010·The Journal of Antibiotics·Roberta PozziStefano Donadio
Jan 12, 2011·Antimicrobial Agents and Chemotherapy·Daniela JabésStefano Donadio
Apr 8, 2011·Current Pharmaceutical Biotechnology·Jun-ichi NagaoKenji Sonomot
Mar 13, 2012·Annual Review of Biochemistry·Patrick J Knerr, Wilfred A van der Donk
May 24, 2012·Journal of Natural Products·Carlo MazzettiStefano Donadio
Oct 5, 2012·Chemical Communications : Chem Comm·Yanxiang ShiWilfred A van der Donk
Nov 21, 2012·Natural Product Reports·Paul G ArnisonWilfred A van der Donk
Mar 12, 2013·Journal of Bacteriology·Emma J SherwoodMervyn J Bibb
Jan 16, 2014·Journal of Natural Products·Sonia I MaffioliStefano Donadio
Jun 1, 2014·Bioorganic Chemistry·Alethea B Tabor
Dec 17, 2014·Antimicrobial Agents and Chemotherapy·Alexander J LepakDavid R Andes
Jan 13, 2015·ACS Chemical Biology·Sonia I MaffioliStefano Donadio