Pattern-Based Genome Mining of Marine Actinomycetes Uncovers New Antibiotic 'Indanopyrrole A'

Researchers at the Scripps Institution of Oceanography, UC San Diego, in the United States have found the new antibiotic natural products indanopyrrole A and B in marine-derived actinomycetes. The genus Streptomyces is a group of microbes that has yielded many clinical antibiotics and anticancer compounds from land soil, but the biosynthetic potential of strains isolated from the sea has been relatively less explored.

Linking to 'orphan' gene clusters in 20 MAR4 genomes

The researchers applied pattern-based genome mining to the MAR4 lineage of Streptomyces, which is isolated mainly from the sea. They identified for the first time a class of natural products, halogenated pyrroloketoindanes, and linked them bioinformatically to biosynthetic gene clusters (BGCs) of unknown function found in 20 MAR4 genomes. Indanopyrrole A showed strong, broad-spectrum antibacterial activity against clinically important pathogens.

By comparison with the gene cluster of the similar compound indanomycin, they also gained new clues about the final cyclization and molecule release steps for this class. A search of public databases showed that this gene cluster is rare, and the researchers judged that there is room to find more compounds of the same class. However, the antibacterial activity is a laboratory-stage result, and efficacy and safety in infected animal models or in people have not been confirmed.