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23 páginas, 6 figuras, 5 tablas ; Root mutualistic microbes can modulate the production of plant secondary metabolites affecting plant–herbivore interactions. Still, the main mechanisms underlying the impact of root mutualists on herbivore performance remain ambiguous. In particular, little is known about how changes in the plant metabolome induced by root mutualists affect the insect metabolome and postlarval development. By using bioassays with tomato plants (Solanum lycopersicum), we analyzed the impact of the arbuscular mycorrhizal fungus Rhizophagus irregularis and the growth-promoting fungus Trichoderma harzianum on the plant interaction with the specialist insect herbivore Manduca sexta. We found that root colonization by the mutualistic microbes impaired insect development, including metamorphosis. By using untargeted metabolomics, we found that root colonization by the mutualistic microbes altered the secondary metabolism of tomato shoots, leading to enhanced levels of steroidal glycoalkaloids. Untargeted metabolomics further revealed that root colonization by the mutualists affected the metabolome of the herbivore, leading to an enhanced accumulation of steroidal glycoalkaloids and altered patterns of fatty acid amides and carnitine-derived metabolites. Our results indicate that the changes in the shoot metabolome triggered by root mutualistic microbes can cascade up altering the metabolome of the insects feeding on the colonized plants, thus affecting the insect development. ; The work of D.P. was supported by the European Union's Horizon 2020 research and innovation program (Microbe-Induced Resistance, MiRA project), grant agreement no. 765290. D.P., F.V., A.W., N.M.v.D. and A.M.-M. gratefully acknowledge the support of iDiv funded by the German Research Foundation (DFG–FZT 118, 202548816). A.M.-M. acknowledges funding from the program for attracting talent to Salamanca from the Fundación Salamanca Ciudad de Cultura y Saberes and Ayuntamiento de Salamanca; the program to support junior researchers to obtain third-party funding from Friedrich-Schiller-Universität Jena (DRM/2015-02); Junta de Castilla y León and European Union (ERDF "Europe drives our growth"; CLU-2019-05—IRNASA /CSIC Unit of Excellence); and the research network RED2018-102407-T from the Spanish Ministry of Science and Innovation and Feder funds. ; Peer reviewed

The decriminalization of cannabis and the growing interest in cannabinoids as therapeutics require efficient methods to discover novel compounds and monitor cannabinoid levels in human samples and products. However, current methods are limited by the structural diversity of the active compounds. Here, we construct a G-protein coupled receptor-based yeast whole-cell biosensor, optimize it to achieve high sensitivity and dynamic range, and prove its effectiveness in three real-life applications. First, we screen a library of compounds to discover two novel agonists and four antagonists and demonstrate that our biosensor can democratize GPCR drug discovery by enabling low-cost high-throughput analysis using open-source automation. Subsequently, we bioprospect 54 plants to discover a novel phytocannabinoid, dugesialactone. Finally, we develop a robust portable device, analyze body-fluid samples, and confidently detect illicit synthetic drugs like "Spice"/"K2". Taking advantage of the extensive sensing repertoire of GPCRs, this technology can be extended to detect numerous other compounds.