ArticleNature communications2026
Mode of action guided metagenomic natural product discovery reveals convergent evolution of a ClpP-targeting motif.
Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1 citing paper in PubMed.
- Resistance-CONKAT-seq Guided Discovery of a ClpP Active Natural Product from a Soil Metagenome.ACS chemical biology · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors.
Funding
Abstract
The discovery of natural products with specific modes of action from metagenomes remains challenging. Here, we present resistance-CONKAT-seq, a pipeline that links biosynthetic gene clusters (BGCs) to self-resistance genes, enabling identification of metabolites with desired molecular targets. Using clpP-directed resistance-CONKAT-seq, we identify the calprotamides, which activate native ClpP and enhance its activity. Cryo-EM and bioinformatic analyses reveal that the calprotamides' medium-chain N-acylphenylalanine substructure is a convergently evolved ClpP-targeting motif and identify additional BGCs predicted to encode this moiety, including some with co-localized clp genes. The synthesis of structures bioinformatically inspired by two such clp-linked BGCs, desmethyl jomthonic acid C and tuscamide, reveals that both enhance ClpP activity. Extending our bioinformatically guided synthesis study to additional BGCs lacking nearby clp genes shows that ClpP activity enhancement correlated with antibacterial activity, with the strongest enhancers exhibiting narrow-spectrum antibiotic activity. These findings establish N-acylphenylalanine as a previously unrecognized but common natural motif for targeting ClpP, which should help guide the discovery of both natural and synthetic ClpP modulators for antibiotic and anticancer development. Resistance-CONKAT-seq offers a scalable method for exploring biosynthetic dark matter for metabolites with desired modes of action.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.