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In <jats:italic>Streptomyces roseosporus<\/jats:italic> (which produces daptomycin widely used for treatment of human infections), deletion of <jats:italic>bldD<\/jats:italic> notably reduced daptomycin production, but enhanced sporulation. BldD stimulated daptomycin production by directly activating transcription of <jats:italic>dpt<\/jats:italic> structural genes and <jats:italic>dptR3<\/jats:italic> (which encodes an indirect activator of daptomycin production), and repressed its own gene. BldD\u2010binding sites on promoter regions of <jats:italic>dptE<\/jats:italic>, <jats:italic>dptR3<\/jats:italic>, and <jats:italic>bldD<\/jats:italic> were all found to contain BldD box\u2010like sequences, facilitating prediction of new BldD targets. Two <jats:italic>Streptomyces<\/jats:italic> global regulatory genes, <jats:italic>adpA<\/jats:italic> and <jats:italic>afsR<\/jats:italic>, were confirmed to be directly activated by BldD. The protein AfsR was shown to act as an activator of daptomycin production, but a repressor of development. BldD directly represses nine key developmental genes. In <jats:italic>Streptomyces avermitilis<\/jats:italic> (which produces effective anthelmintic agents avermectins), BldD homolog (BldDsav) directly activates avermectin production through <jats:italic>ave<\/jats:italic> structural genes and cluster\u2010situated activator gene <jats:italic>aveR<\/jats:italic>. This is the first report that BldD activates antibiotic biosynthesis both directly and via a cascade mechanism. BldD homologs are widely distributed among <jats:italic>Streptomyces<\/jats:italic>, our findings suggest that BldD may activate antibiotic production in other <jats:italic>Streptomyces<\/jats:italic> species.<\/jats:p>","DOI":"10.1111\/mmi.14405","type":"journal-article","created":{"date-parts":[[2019,10,19]],"date-time":"2019-10-19T08:05:45Z","timestamp":1571472345000},"page":"123-142","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["BldD, a master developmental repressor, activates antibiotic production in two <i>Streptomyces<\/i> species"],"prefix":"10.1111","volume":"113","author":[{"given":"Hao","family":"Yan","sequence":"first","affiliation":[{"name":"State Key Laboratory of Agrobiotechnology and College of Biological Sciences China Agricultural University Beijing 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