Thiopeptides encoding biosynthetic gene clusters mined from bacterial genomes

Area of Science:

• Microbiology
• Biochemistry
• Natural Products Chemistry

Background:

• The rise of antimicrobial resistance (AMR) threatens the post-antibiotic era, creating an urgent need for novel antibiotics.
• Ribosomally synthesized and post-translationally modified peptides (RiPPs), particularly thiopeptides, are a promising class of natural products with antimicrobial activity against Gram-positive pathogens.
• Thiopeptides are characterized by complex post-translational modifications (PTMs), including a core [4+2] cycloaddition.

Purpose of the Study:

• To identify novel thiopeptide biosynthetic gene clusters (BGCs) through genome mining.
• To expand the molecular diversity of natural products with potential medicinal applications.
• To provide a foundation for experimental validation and discovery of new thiopeptides.

Main Methods:

• Utilized genome mining strategies with freely available bioinformatics tools.
• Analyzed bacterial genomes, with a focus on the class Actinobacteria.
• Identified eight novel putative thiopeptide-encoding BGCs.

Main Results:

• Successfully identified eight novel putative thiopeptide BGCs from diverse bacterial genomes.
• The majority of identified BGCs were found within the Actinobacteria class.
• The findings support the potential for discovering new thiopeptide natural products.

Conclusions:

• Genome mining is an effective strategy for discovering novel RiPPs, including thiopeptides.
• The identified BGCs represent promising targets for future experimental research.
• This work contributes to the ongoing effort to combat antimicrobial resistance by expanding the pipeline of potential new antibiotics.