Genome-Mining Based Discovery of Pyrrolomycin K and L from the Termite-Associated Micromonospora sp. RB23

Summary

Scientists discovered two new antimicrobial compounds called pyrrolomycins from bacteria living in termites using genome sequencing and chemical analysis. These compounds contain chlorine atoms and are related to known antibiotics. The research shows how the bacteria protects itself from its own antimicrobial compounds through chemical modifications, offering insights into developing new antibiotics.

Background

Natural products from symbiotic microbes represent a rich source of bioactive molecules. Micromonospora species are known producers of structurally diverse natural products. Actinomycetota species associated with insects have shown antimicrobial capabilities relevant to protective symbiosis.

Objective

To investigate the antimicrobial activity of termite-associated Micromonospora sp. RB23 through genome mining and identify the secondary metabolites responsible for its bioactivity. The study aimed to elucidate the chemical structure and biosynthetic origins of novel pyrrolomycin derivatives.

Results

Two novel pyrrolomycin derivatives were isolated: N-methylated pyrrolomycin K (3) and N-acetyl-cysteinylated pyrrolomycin L (5). A type I polyketide synthase biosynthetic gene cluster encoding five halogenases was identified. Pyrrolomycin L showed weak antimicrobial activity against S. aureus and E. coli, while N-methylation abolished activity.

Conclusion

N-methylation and mycothiol-based conjugation represent detoxification mechanisms enhancing self-tolerance in pyrrolomycin production. The study demonstrates the power of genome mining combined with ecological insights for discovering novel chemical scaffolds and biosynthetic chemistry, broadening knowledge of pyrrolomycin chemical diversity.
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