Related Experiment Video

Updated: May 3, 2026

Phage-Mediated Genetic Manipulation of the Lyme Disease Spirochete Borrelia burgdorferi
09:01

Phage-Mediated Genetic Manipulation of the Lyme Disease Spirochete Borrelia burgdorferi

Published on: September 28, 2022

2.5K

Synthesis of full length and truncated microcin B17 analogues as DNA gyrase poisons

Robert E Thompson1, Frédéric Collin, Anthony Maxwell

  • 1School of Chemistry, The University of Sydney, NSW 2006, Australia. richard.payne@sydney.edu.au.

Organic & Biomolecular Chemistry
|January 23, 2014
PubMed

Insights

Truncated Microcin B17 (MccB17) analogues show enhanced DNA gyrase poisoning activity. However, the N-terminal region is crucial for MccB17

Area of Science:

  • Biochemistry and Molecular Biology
  • Peptide Synthesis and Analysis
  • Antimicrobial Drug Discovery

Background:

  • Microcin B17 (MccB17) is a unique peptide antibiotic characterized by thiazole and oxazole heterocycles.
  • MccB17 functions by stabilizing the DNA gyrase-DNA cleavage complex, acting as a potent gyrase poison.
  • Understanding the structural basis of MccB17's activity is crucial for developing novel antimicrobial agents.

Purpose of the Study:

  • To investigate the key structural requirements for the DNA gyrase-poisoning activity of Microcin B17.
  • To synthesize and characterize a library of MccB17 analogues with modifications in the N-terminal region.
  • To elucidate the role of specific MccB17 structural features in both gyrase inhibition and antibacterial efficacy.

Main Methods:

  • Employed Fmoc-strategy solid-phase peptide synthesis for the preparation of MccB17 analogues.
  • Utilized solution-phase fragment assembly for the construction of truncated and full-length MccB17 sequences.
  • Assessed the ability of synthetic peptides to stabilize the gyrase-DNA cleavage complex and evaluated antibacterial activity.

Main Results:

  • Synthetic MccB17 analogues lacking the N-terminal glycine-rich region demonstrated potent stabilization of the gyrase-DNA cleavage complex.
  • These truncated analogues exhibited increased potency in gyrase poisoning compared to full-length MccB17.
  • Antibacterial activity was reduced in truncated analogues, suggesting the N-terminal region facilitates cellular uptake.

Conclusions:

  • The N-terminal portion of Microcin B17 is not essential for DNA gyrase poisoning but plays a significant role in its antibacterial efficacy.
  • Truncation of the N-terminal region enhances the intrinsic gyrase-poisoning potency of MccB17 analogues.
  • The findings suggest that the N-terminal region of MccB17 is critical for efficient cellular uptake, impacting overall antimicrobial activity.

More Related Videos

Author Spotlight: Characterizing DNA G-Quadruplex by Bis-3-Chloropiperidine Based Chemical Mapping05:32

Author Spotlight: Characterizing DNA G-Quadruplex by Bis-3-Chloropiperidine Based Chemical Mapping

Published on: May 12, 2023

2.0K
The Logic, Experimental Steps, and Potential of Heterologous Natural Product Biosynthesis Featuring the Complex Antibiotic Erythromycin A Produced Through E. coli10:41

The Logic, Experimental Steps, and Potential of Heterologous Natural Product Biosynthesis Featuring the Complex Antibiotic Erythromycin A Produced Through E. coli

Published on: January 13, 2013

18.0K

Related Concept Videos

Inhibitors of Bacterial DNA Synthesis01:28

Inhibitors of Bacterial DNA Synthesis

Bacterial pathogens depend on precise and efficient DNA replication to sustain infection. Two type II topoisomerases—DNA gyrase and topoisomerase IV—are critical to this process, as they resolve DNA supercoiling and unlink chromosomes during replication. Fluoroquinolones, synthetic derivatives of quinolones, exploit this mechanism by stabilizing the transient DNA–enzyme cleavage complex, preventing strand religation, and causing lethal double-strand breaks. These...
130
Inhibitors of Bacterial Protein Synthesis01:25

Inhibitors of Bacterial Protein Synthesis

Aminoglycosides constitute a highly potent class of bactericidal antibiotics that exert their antimicrobial effects by targeting the bacterial ribosome, specifically disrupting protein synthesis. These polycationic molecules consist of amino-modified sugars linked via glycosidic bonds to an aminocyclitol core such as 2-deoxystreptamine or streptamine. Their strong positive charges facilitate tight binding to the negatively charged phosphate backbone of ribosomal RNA (rRNA), primarily at the 16S...
106
Inhibitors of Gram-positive Cell Wall Synthesis01:23

Inhibitors of Gram-positive Cell Wall Synthesis

Bacterial cell walls are typically rigid structures composed mainly of peptidoglycan, a mesh-like polymer that provides mechanical strength and maintains cell shape. The synthesis of peptidoglycan is a crucial process in bacterial growth and serves as a primary target for many antibiotics.Mechanism of Action of Beta-Lactam AntibioticsBeta-lactam antibiotics, such as penicillin, inhibit peptidoglycan synthesis in actively growing cells. These antibiotics share a characteristic four-membered...
191
DNA Bacteriophages01:26

DNA Bacteriophages

Bacteriophages, or phages, are viruses that specifically infect bacteria, utilizing their genetic material to hijack host cellular machinery for replication. DNA bacteriophages employ single-stranded DNA (ssDNA) or double-stranded DNA (dsDNA) genomes. These phages exhibit diverse replication strategies and host interactions, influencing their ecological roles and applications in biotechnology and medicine.ssDNA BacteriophagesssDNA phages, with their small genomes, utilize unique strategies to...
1.6K
Coordination of Gene Expression Processes in Bacteria01:29

Coordination of Gene Expression Processes in Bacteria

The DNA replication, transcription, and translation processes are intricately coupled in bacteria, allowing efficient gene expression and rapid protein synthesis. While this physical and functional coordination is advantageous, it introduces challenges that bacteria overcome through specific regulatory mechanisms.Coupling of Replication, Transcription, and TranslationThe coupling of replication, transcription, and translation is a hallmark of bacterial gene expression. As the replisome unwinds...
1.1K
Genomic DNA in Prokaryotes00:46

Genomic DNA in Prokaryotes

The genome of most prokaryotic organisms consists of double-stranded DNA organized into one circular chromosome in a region of cytoplasm called the nucleoid. The chromosome is tightly wound, or supercoiled, for efficient storage. Prokaryotes also contain other circular pieces of DNA called plasmids. These plasmids are smaller than the chromosome and often carry genes that confer adaptive functions, such as antibiotic resistance.
Genomic Diversity in Bacteria
Although bacterial genomes are much...
42.4K