On the trail of new drug candidates
The hidden potential in the genomes of peatland bacteria
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Many of our most important medicines—especially antibiotics—originate from substances that bacteria produce in nature. Bacteria use these molecules as biochemical weapons against competitors or to capture nutrients from their surroundings. A new study reveals the scale of this microbial toolkit in challenging habitats. The research team brought together scientists from the Cluster of Excellence »Balance of the Microverse« at the University of Jena, Heinrich Heine University Düsseldorf, the University of Delaware, and the German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig. Together, they took a closer look at the genetic material of peatland bacteria.
More than 8,000 unexplored blueprints
For their analysis, the researchers examined peat samples from the Schlöppnerbrunnen fen in Bavaria’s Fichtelgebirge mountains. Using high- throughput sequencing and metagenomics, they analysed the genetic material of the local microbial community and identified almost 9,700 biosynthetic gene clusters—sections of DNA containing instructions for producing biologically active compounds.
Even after the team filtered out incomplete gene fragments, more than 8,000 reliable gene clusters remained. Remarkably, around 97 per cent could not be assigned to any previously known gene cluster family in global databases. They therefore represent a largely uncharted biochemical landscape.
»Even a small peatland harbours an astonishing diversity of blueprints for natural products. Many come from microorganisms that are still difficult to study in the laboratory,« explains first author Zander Human of the University of Jena.
Having a blueprint does not mean using it
A blueprint in a bacterium’s DNA does not automatically mean that the corresponding substance is produced in nature. The team therefore went a step further and measured messenger RNA (mRNA) to assess which genes were actively used in the peatland.
The findings challenge existing assumptions: only around 9 to 27 per cent of the gene clusters examined were active in their natural setting. Some bacterial groups with particularly extensive genetic potential—sometimes carrying more than 20 different blueprints in their genomes—remained largely inactive in the peatland.
Instead, bacteria known as Acidobacteriota have been the most active. Although their genetic repertoires were comparatively modest, they accounted for roughly two-thirds of the measured signals from natural product genes. The data also revealed a clear pattern: activity of these genes in Acidobacteriota was particularly high alongside activity of genes for enzymes that break down complex plant material. Natural product biosynthesis in these bacteria therefore appears closely linked to how they obtain nutrients.
»The number of blueprints alone tells us little about what a microorganism actually does in its habitat. We also need to understand the conditions under which it switches these genes on,« emphasises co-author Dr Carl-Eric Wegner of the universities of Jena and Düsseldorf.
Understanding microbial balance in peatlands
The findings align closely with the research focus of the Cluster of Excellence »Balance of the Microverse«, which investigates how microbial communities interact and maintain balance within complex ecosystems.
»Peatlands are dynamic habitats with steep environmental gradients, for example in oxygen levels and nutrient availability. Our study clearly shows that natural product biosynthesis does not occur in isolation but is closely integrated into the role of microorganisms in biogeochemical cycles in complex systems,« explains Professor Kirsten Küsel, co-author of the study and spokesperson for the Cluster of Excellence.
A new perspective for pharmaceutical research
The study offers an important insight for the search for future medicines: screening for genomes with the largest number of blueprints is insufficient. What matters is the ecological setting in which microorganisms actually put their genetic toolkit to use. Previously overlooked groups such as Acidobacteriota are therefore attracting growing interest in natural product research.
Fresh directions for future drug discovery
The findings have far-reaching implications for pharmaceutical biotechnology and the targeted search for new drug candidates. Natural product research has traditionally focused on genome screening in well-known bacterial groups such as actinobacteria and pseudomonads, which harbour extensive libraries of biosynthetic genes.
Yet, as the current study shows, these seemingly gifted producers can remain largely silent in their natural environment. This suggests a change in approach: to activate silent gene clusters in the laboratory, researchers need to recreate specific ecological cues from the organisms’ natural habitats—for example, by supplying complex plant fibres or particular nutrient signals.
Previously overlooked groups that are difficult to grow in the laboratory, such as Acidobacteriota, are also moving into the spotlight. Studying them systematically could provide access to entirely new classes of molecules, potentially offering future avenues for tackling antimicrobial resistance or severe inflammatory diseases.
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