Antimicrobial nucleoside antibiotics targeting cell wall assembly: recent advances in structure-function studies and
Michael Winn1, Rebecca J M Goss, Ken-ichi Kimura
1School of Chemistry, University of East Anglia, Norwich, NR4 7TJ, UK.
Natural Product Reports
|January 30, 2010
Summary
New antibiotics targeting Gram-negative bacteria are urgently needed. This review covers nucleoside natural products that inhibit MraY, a key enzyme in bacterial cell wall synthesis, and discusses biosynthetic studies.
Area of Science:
- Microbiology
- Natural Products Chemistry
- Drug Discovery
Background:
- The urgent need for novel antibiotics, particularly against Gram-negative bacteria, is highlighted due to a scarcity of new drugs in recent decades.
- Existing antibiotics have limited structural diversity, with only four new classes introduced in the past 40 years.
- Bacterial translocase MraY, crucial for peptidoglycan biosynthesis, and fungal chitin synthase are identified as key targets for nucleoside natural product antibiotics.
Purpose of the Study:
- To review the current landscape of antibiotic development, focusing on challenges in targeting Gram-negative pathogens.
- To explore the role of nucleoside natural products as potential therapeutic agents.
- To summarize biosynthetic studies on important families of nucleoside antibiotics.
Main Methods:
- Literature review of scientific publications on antibiotic discovery, bacterial cell wall biosynthesis, and natural product chemistry.
- Analysis of existing data on nucleoside natural product antibiotics targeting MraY and chitin synthase.
- Compilation and discussion of biosynthetic pathways for nikkomycin, caprazamycin, and pacidamycin/mureidomycin families.
Main Results:
- Nucleoside natural products represent a promising class of compounds with potential against challenging bacterial infections.
- MraY and chitin synthase are validated targets for these agents, offering avenues for novel drug development.
- Review of biosynthetic studies provides insights into the production and potential modification of these valuable natural products.
Conclusions:
- Continued research into nucleoside natural products is essential for developing new antibiotics to combat antimicrobial resistance.
- Understanding the biosynthesis of these compounds can facilitate the development of semi-synthetic derivatives with improved efficacy.
- Targeting essential bacterial pathways like peptidoglycan synthesis remains a critical strategy in the fight against Gram-negative infections.
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