Modifying the Lantibiotic Mutacin 1140 for Increased Yield, Activity, and Stability

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Mutacin 1140 Lantibiotic Variants Are Efficacious Against Clostridium difficile Infection

Lantibiotics offer an untapped pipeline for the development of novel antibiotics to treat serious Gram-positive (+) infections including Clostridium difficile. Mutacin 1140 (MU1140) is a lantibiotic produced by Streptococcus mutans and acts via a novel mechanism of action, which may limit the development of resistance. This study sought to identify a lead compound for the treatment of C. diffic...

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Biosynthesis and transport of the lantibiotic mutacin 1140 produced by Streptococcus mutans.

UNLABELLED Lantibiotics are ribosomally synthesized peptide antibiotics composed of an N-terminal leader peptide that is cleaved to yield the active antibacterial peptide. Significant advancements in molecular tools that promote the study of lantibiotic biosynthesis can be used in Streptococcus mutans. Herein, we further our understanding of leader peptide sequence and core peptide structural r...

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Genetic and biochemical analysis of mutacin 1140, a lantibiotic from Streptococcus mutans.

Streptococcus mutans JH1000 and its derivatives were previously shown (J. D. Hillman, K. P. Johnson, and B. I. Yaphe, Infect. Immun. 44:141-144, 1984) to produce a low-molecular-weight, broad-spectrum bacteriocin-like inhibitory substance (BLIS). The thermosensitive vector pTV1-OK harboring Tn917 was used to isolate a BLIS-deficient mutant, DM25, and the mutated gene was recovered by shotgun cl...

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Biochemical structural analysis of the lantibiotic mutacin II.

Mutacin II is a post-translationally modified lantibiotic peptide secreted by Streptococcus mutans T8, which inhibits the energy metabolism of sensitive cells. The deduced amino acid sequence of promutacin II is NRWWQGVVPTVSYECRMNSWQHVFTCC, which is capable of forming three thioether bridges. It was not obvious, however, how the three thioether bridges are organized. To examine the bridging, th...

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The leader peptide of mutacin 1140 has distinct structural components compared to related class I lantibiotics

Lantibiotics are ribosomally synthesized peptide antibiotics composed of an N-terminal leader peptide that promotes the core peptide's interaction with the post translational modification (PTM) enzymes. Following PTMs, mutacin 1140 is transported out of the cell and the leader peptide is cleaved to yield the antibacterial peptide. Mutacin 1140 leader peptide is structurally unique compared to o...

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ژورنال

عنوان ژورنال: Applied and Environmental Microbiology

سال: 2018

ISSN: 0099-2240,1098-5336

DOI: 10.1128/aem.00830-18