Soils harbor some of the most diverse microbiomes on Earth. Interactions within these microbial communities are often mediated by natural products, many functioning as chemical signals. Specialized metabolites known as arginoketides, or arginine-derived polyketides, have been linked to mediate these interactions. However, the effect of linear arginoketides on soil microalgae has not yet been investigated. Here, we report that Streptomyces mashuensis DSM40221 produces the linear arginoketide neotetrafibricin A, and show that it exhibits algicidal activity against the green alga Chlamydomonas reinhardtii and induces production of orsellinic acid and derivatives encoded by the silent ors biosynthetic gene cluster (BGC) in the fungus Aspergillus nidulans. Thus, neotetrafibricin serves as an inter-kingdom signaling molecule. Genome mining identified the neotetrafibricin BGC in S. mashuensis. Disrupting the first polyketide synthase gene abolished neotetrafibricin production. Further mutational studies identified two neotetrafibricin congeners, including the novel neotetrafibricin C, which contains a terminal guanidino group. Structure-activity relationship analyses revealed that neither the terminal amino group nor the sugar moiety is essential for its algicidal activity or the induction of the ors BGC in the fungus. These findings expand the understanding of linear arginoketides in microbial ecology and highlight their potential as multifunctional signaling compounds in soil environments.