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Here, we report tamastrepamides, a family of alkylproline\u2010containing cyclodepsipeptides from\n                    <jats:italic>Streptomyces<\/jats:italic>\n                    sp. HL19 that function as interspecific effectors by selectively downregulating transcription of the master developmental regulator\n                    <jats:italic>bldD<\/jats:italic>\n                    . The horizontally acquired\n                    <jats:italic>tam<\/jats:italic>\n                    biosynthetic gene cluster is conspicuously enriched in rare TTA codons, functionally coupling its expression to the developmentally regulated tRNA\n                    <jats:sup>Leu<\/jats:sup>\n                    (UAA) encoded by\n                    <jats:italic>bldA<\/jats:italic>\n                    . Tamastrepamide A arrests sporulation and diminishes secondary metabolite production in diverse actinomycetes without inhibiting vegetative growth, thereby chemically phenocopying a \u0394\n                    <jats:italic>bldD<\/jats:italic>\n                    mutant. Promoter\u2010specific reporter assays demonstrate that tamastrepamide A reduces\n                    <jats:italic>bldD<\/jats:italic>\n                    promoter activity, while the producer strain is intrinsically insensitive to this effect. Production of tamastrepamides strictly depends on the functionally specialized tRNA\n                    <jats:sup>Leu<\/jats:sup>\n                    (UAA), revealing a self\u2010contained regulatory circuit in which a developmentally gated metabolite disables the same developmental program in neighboring competitors. These findings illustrate an ecological strategy in which a developmentally regulated biosynthetic pathway produces a diffusible metabolite that interferes with the sporulation program of competing actinomycetes.\n                  <\/jats:p>","DOI":"10.1002\/anie.4866271","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T04:17:19Z","timestamp":1790309839000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A tRNA\u2010Gated Cyclodepsipeptide Pathway Produces a Chemical Effector That Disarms Bacterial Development"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-7763-551X","authenticated-orcid":false,"given":"Yanwei","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine Zhongnan Hospital School of Pharmaceutical Sciences TaiKang Center for Life and Medical Sciences Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Ministry of Education) Wuhan University  Wuhan PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiting","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine Zhongnan Hospital School of Pharmaceutical Sciences TaiKang Center for Life and Medical Sciences Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Ministry of Education) Wuhan University  Wuhan PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifen","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine Zhongnan Hospital School of Pharmaceutical Sciences TaiKang Center for Life and Medical Sciences Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Ministry of Education) Wuhan University  Wuhan PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4122-9816","authenticated-orcid":false,"given":"Weixin","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine Zhongnan Hospital School of Pharmaceutical Sciences TaiKang Center for Life and Medical Sciences Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Ministry of Education) Wuhan University  Wuhan PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9732-1123","authenticated-orcid":false,"given":"Fan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine Zhongnan Hospital School of Pharmaceutical Sciences TaiKang Center for Life and Medical Sciences Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Ministry of Education) Wuhan University  Wuhan PR 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