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Microbisporicin

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https://www.readbyqxmd.com/read/26346738/a-novel-microbisporicin-producer-identified-by-early-dereplication-during-lantibiotic-screening
#1
Lucia Carrano, Monica Abbondi, Paola Turconi, Gianpaolo Candiani, Flavia Marinelli
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...
2015: BioMed Research International
https://www.readbyqxmd.com/read/25939852/a-rela-dependent-regulatory-cascade-for-auto-induction-of-microbisporicin-production-in-microbispora-corallina
#2
Lorena T Fernández-Martínez, Juan P Gomez-Escribano, Mervyn J Bibb
Microbisporicin is a potent type I lantibiotic produced by the rare actinomycete Microbispora corallina that is in preclinical trials for the treatment of infections caused by methicillin-resistant isolates of Staphylococcus aureus (MRSA). Analysis of the gene cluster for the biosynthesis of microbisporicin, which contains two unique post-translationally modified residues (5-chlorotryptophan and 3, 4-dihydroxyproline), has revealed an unusual regulatory mechanism that involves a pathway-specific extracytoplasmic function sigma factor (MibX)/anti-sigma factor (MibW) complex and an additional transcriptional regulator MibR...
August 2015: Molecular Microbiology
https://www.readbyqxmd.com/read/25697059/perspectives-on-lantibiotic-discovery-where-have-we-failed-and-what-improvements-are-required
#3
EDITORIAL
Stephanie Kate Sandiford
The increasing resistance of bacteria to conventional antimicrobial therapy within both the nosocomial and community environment has enforced the urgent requirement for the discovery of novel agents. This has stimulated increased research efforts within the field of lantibiotic discovery. Lantibiotics are ribosomally synthesised, post-translationally modified antimicrobial peptides that exhibit antimicrobial activity against a range of multi-drug-resistant (MDR) bacteria. The success of these agents as a novel treatment of MDR infections is exemplified by: the clinical development of MU1140 (mutacin 1140) and NAI-107 (microbisporicin), which are in late pre-clinical trials against gram-positive bacteria; NVB302 that has completed Phase I clinical trials for the treatment of Clostridium difficile infections and; duramycin that has completed Phase II clinical trials in the treatment of cystic fibrosis...
April 2015: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/21478362/feed-forward-regulation-of-microbisporicin-biosynthesis-in-microbispora-corallina
#4
Lucy Foulston, Mervyn Bibb
Lantibiotics are ribosomally synthesized, posttranslationally modified peptide antibiotics. Microbisporicin is a potent lantibiotic produced by the actinomycete Microbispora corallina and contains unique chlorinated tryptophan and dihydroxyproline residues. The biosynthetic gene cluster for microbisporicin encodes several putative regulatory proteins, including, uniquely, an extracytoplasmic function (ECF) σ factor, σ(MibX), a likely cognate anti-σ factor, MibW, and a potential helix-turn-helix DNA binding protein, MibR...
June 2011: Journal of Bacteriology
https://www.readbyqxmd.com/read/20628010/microbisporicin-gene-cluster-reveals-unusual-features-of-lantibiotic-biosynthesis-in-actinomycetes
#5
Lucy C Foulston, Mervyn J Bibb
Lantibiotics are ribosomally synthesized, posttranslationally modified peptide antibiotics. The biosynthetic gene cluster for microbisporicin, a potent lantibiotic produced by the actinomycete Microbispora corallina containing chlorinated tryptophan and dihydroxyproline residues, was identified by genome scanning and isolated from an M. corallina cosmid library. Heterologous expression in Nonomuraea sp. ATCC 39727 confirmed that all of the genes required for microbisporicin biosynthesis were present in the cluster...
July 27, 2010: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/18215770/determining-the-structure-and-mode-of-action-of-microbisporicin-a-potent-lantibiotic-active-against-multiresistant-pathogens
#6
Franca Castiglione, Ameriga Lazzarini, Lucia Carrano, Emiliana Corti, Ismaela Ciciliato, Luciano Gastaldo, Paolo Candiani, Daniele Losi, Flavia Marinelli, Enrico Selva, Francesco Parenti
Antibiotics blocking bacterial cell wall assembly (beta-lactams and glycopeptides) are facing a challenge from the progressive spread of resistant pathogens. Lantibiotics are promising candidates to alleviate this problem. Microbisporicin, the most potent antibacterial among known comparable lantibiotics, was discovered during a screening applied to uncommon actinomycetes. It is produced by Microbispora sp. as two similarly active and structurally related polypeptides (A1, 2246-Da and A2, 2230-Da) of 24 amino acids linked by 5 intramolecular thioether bridges...
January 2008: Chemistry & Biology
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