New Glycosylated Polyene Macrolides: Refining the Ore from Genome Mining.

Area of Science:

• Microbiology
• Natural Products Chemistry
• Bioinformatics

Background:

• Glycosylated polyene macrolides, including amphotericin B, are vital antifungal agents.
• Amphotericin B is a gold-standard treatment for systemic mycoses but has severe toxic side effects.
• Developing safer antifungal alternatives is a critical objective in medicine.

Purpose of the Study:

• To review recent studies on discovering new polyene natural products.
• To assess how bioinformatics and genomics can prioritize silent polyene gene clusters for investigation.
• To improve the discovery of novel, safer antifungal antibiotics.

Main Methods:

• Bioinformatic analysis of microbial genome sequences to identify polyene biosynthetic gene clusters.
• Characterization of novel polyenes with new backbones, oxygenations, and sugar residues.
• Review of recent experimental studies on polyene natural products.

Main Results:

• Over 250 polyene gene clusters have been identified through bioinformatics.
• New polyenes with enhanced water-solubility and reduced hemolytic activity have been characterized.
• Advances enable prioritization of previously uncharacterized, silent polyene clusters.

Conclusions:

• Genomic and bioinformatic approaches are powerful tools for discovering new antifungal agents.
• Identifying and investigating silent polyene clusters can lead to the development of improved antifungal antibiotics.
• This strategy holds promise for overcoming the limitations of current antifungal therapies.