Updated project metadata. Microbial consortia consist of a multitude of prokaryotic and eukaryotic microorganisms. Their interaction is critical for the functioning of ecosystems. Until now, there is limited knowledge about the communication signals determining the interaction between bacteria and fungi and how they influence microbial consortia. Here, we discovered that bacterial low molecular weight arginine-derived polyketides trigger the production of distinct natural products in fungi. These compounds are produced by actinomycetes found on all continents except Antarctica and are characterized by an arginine-derived positively charged group linked to a linear or cyclic polyene moiety. Producer bacteria can be readily isolated from soil as well as fungi that decode the signal and respond with the biosynthesis of natural products. Both arginine-derived polyketides and the compounds produced by fungi in response shape microbial interactions.