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In this study, we investigated the role of the highly conserved orphan response regulator OrrA in\n                    <jats:italic>Streptomyces venezuelae<\/jats:italic>\n                    NRRL B-65442. We show that\n                    <jats:italic>S. venezuelae<\/jats:italic>\n                    \u2206\n                    <jats:italic>orrA<\/jats:italic>\n                    mutants are defective in sporulation and used chromatin immunoprecipitation followed by sequencing to identify five OrrA binding sites\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Tandem-mass-tag proteomics revealed that OrrA directly activates two of these putative target genes,\n                    <jats:italic>wblA<\/jats:italic>\n                    and\n                    <jats:italic>vnz_04640<\/jats:italic>\n                    , a finding consistent with previous work on OrrA in the distantly related\n                    <jats:italic>Streptomyces coelicolor<\/jats:italic>\n                    . We also demonstrate that deleting\n                    <jats:italic>wblA<\/jats:italic>\n                    blocks sporulation and that overexpressing\n                    <jats:italic>wblA<\/jats:italic>\n                    restores sporulation in the \u2206\n                    <jats:italic>orrA<\/jats:italic>\n                    mutant. Additionally, chloramphenicol biosynthesis is upregulated in both the \u2206\n                    <jats:italic>orrA<\/jats:italic>\n                    and \u2206\n                    <jats:italic>wblA<\/jats:italic>\n                    mutants compared with the wild-type strain. Taken together, these results indicate that the primary function of OrrA is to regulate WblA production and that reduced intracellular WblA levels underlie the phenotypes observed in the \u2206\n                    <jats:italic>orrA<\/jats:italic>\n                    mutant.\n                  <\/jats:p>","DOI":"10.1099\/mic.0.001708","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T16:16:26Z","timestamp":1779984986000},"source":"Crossref","is-referenced-by-count":0,"title":["Defining the OrrA regulon and its role in development and antibiotic production in Streptomyces venezuelae NRRL B-65442"],"prefix":"10.1099","volume":"172","author":[{"given":"Kelly-Rose","family":"Tulley","sequence":"first","affiliation":[{"name":"Centre for Microbial Interactions, Norwich Research Park, Norwich, NR4 7UQ, UK"},{"name":"Department of Molecular Microbiology, John Innes Centre, Norwich Research Park, Norwich, NR4 7UH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5016-0235","authenticated-orcid":false,"given":"Lucas","family":"Balis","sequence":"additional","affiliation":[{"name":"Centre for Microbial Interactions, Norwich Research Park, Norwich, NR4 7UQ, UK"},{"name":"Department of Molecular Microbiology, John Innes Centre, Norwich Research Park, Norwich, NR4 7UH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4979-9680","authenticated-orcid":false,"given":"Neil A.","family":"Holmes","sequence":"additional","affiliation":[{"name":"Centre for Microbial Interactions, Norwich Research Park, Norwich, NR4 7UQ, UK"},{"name":"Department of Molecular Microbiology, John Innes Centre, Norwich Research Park, Norwich, NR4 7UH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3799-2600","authenticated-orcid":false,"given":"Ainsley D. 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