Soil myxobacteria yield five new classes of bioactive compounds

Scientists at the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) have significantly expanded the known diversity of soil-dwelling myxobacteria, a group long recognized as a source of natural antibiotics. Over several decades, a team led by Prof. Rolf Müller collected soil samples, with assistance from citizen scientists in the Microbelix project, and isolated previously uncharacterized myxobacteria. The effort increased the number of known families from 11 to 28 and genera from 32 to 90 within the order Myxococcota.

The researchers sequenced the genomes of all 118 newly described strains and found that virtually every genome contained multiple gene clusters for producing natural products never seen before. These biosynthetic gene clusters serve as blueprints for potential active compounds. To make the data accessible, the team created ABC-Myxo, a free, interactive web-based atlas of these gene regions, and the strains will be maintained by the Leibniz Institute DSMZ-German Collection of Microorganisms and Cell Cultures.

From this expanded collection, the team experimentally verified the production of five new classes of bioactive compounds. Myxoquaterines show activity against fungi, sandacrabines against viruses, and sandarazoles against bacteria. New sorangibactin siderophores, which bind iron, were also identified, along with pyxidicyclines, a novel class of topoisomerase inhibitors that interfere with DNA replication.

The findings, published in Advanced Science, demonstrate that exploring understudied microbial diversity can yield structurally novel chemical scaffolds. The researchers emphasize that well-studied microorganisms rarely produce new compounds, whereas the newly isolated myxobacteria offer unparalleled potential for discovering truly novel structures. The work was supported by the Helmholtz Center for Infection Research in collaboration with Saarland University.

Citizen scientists continue to contribute soil samples through the Microbelix project, further expanding the strain collection. The researchers note that the genetic and chemical diversity uncovered so far lays a foundation for developing urgently needed active compounds to treat infectious diseases, though the path from compound discovery to clinical application remains long and uncertain.