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Antimicrobials

Metagenomics for drug discovery

Nature Reviews Microbiology volume 23, page 67 (2025)Cite this article

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Drug discovery is shifting from traditional bioactivity-guided screens of specific cultured bacteria to analysing entire ecosystems that include previously uncultivated microorganisms. Microbial mats harbour a rich and dynamic microbial community that has been explored for natural product discovery. In a recent study, Padhi et al. conduct an ecosystem-level bioinformatic and functional analysis to study the algal–bacterial mats of Chilika Lake, India, in search of potential natural products.

Metagenomics analysis identified hundreds of bacterial metagenome-assembled genomes, primarily from the Proteobacteria, Bacteroidota and Firmicutes phyla. The analysis revealed many biosynthetic gene clusters, with ribosomally synthesized and post-translationally modified peptides (RiPPs) being the most prevalent across different mat samples. RiPPs were bioinformatically assigned to members of the Rheinheimera bacterial genus. The combination of cultivation assays, synthetic biology and chemical synthesis uncovered two biosynthetic pathways in Rheinheimera pleomorphica CP1, a cultivable mat microbiome member, responsible for producing graspetide and spliceotide peptides. These compounds showed varying proteolytic and inhibitory activity in vitro against influenza A virus, herpes simplex virus and lymphocytic choriomeningitis virus.

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  1. Nature Reviews Microbiology http://www.nature.com/nrmicro/

    Agustina Taglialegna

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  1. Agustina Taglialegna
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Correspondence to Agustina Taglialegna.

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Taglialegna, A. Metagenomics for drug discovery. Nat Rev Microbiol 23, 67 (2025). https://doi.org/10.1038/s41579-024-01138-7

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