Plant Coumarins Modulate Natural Product Biosynthesis in a <i>Streptomyces</i> Root Endophyte

The plant microbiome plays a central role in regulating plant health and resilience, providing eco-friendly alternatives to agrochemicals. Plant-associated <i>Streptomyces</i> species are prolific producers of structurally diverse natural products with a demonstrated role in promoting plant growth. Coumarins are prevalent plant metabolites that shape the root microbiome, but their impact on microbial natural product biosynthesis is poorly understood. Here, we demonstrate that the coumarins scopoletin and its glucoside scopolin remodel specialized metabolism in the <i>Arabidopsis</i> root endophyte <i>Streptomyces</i> sp. ATMOS53. Multiomics analyses revealed that the coumarins activate the biosynthesis of the pyrrolizidine alkaloids bohemamines and alter the balance in anthracycline biosynthesis, with reduced production of late-stage anthracycline congeners and accumulation of shunt metabolites earlier in the pathway. These metabolic shifts resulted in a marked reduction of the antimicrobial activity of ATMOS53 against plant-associated <i>Bacillus</i> and <i>Paenibacillus</i> species. Notably, coumarin-mediated repression of anthracycline production was also observed in the established producers <i>Streptomyces peucetius</i> and <i>Streptomyces galilaeus</i>, indicating that the regulatory effect on anthracycline biosynthesis is conserved in streptomycetes. Our findings highlight coumarins as modulators of specialized metabolism of <i>Streptomyces</i> and show the significance of plant-derived chemicals for the control of the biosynthetic capacity of plant-associated microbes.