{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T10:23:22Z","timestamp":1776421402198,"version":"3.51.2"},"reference-count":33,"publisher":"Proceedings of the National Academy of Sciences","issue":"10","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2003,5,13]]},"abstract":"<jats:p>\n            The biosynthesis of most secondary metabolites in different bacteria is strongly depressed by inorganic phosphate. The two-component\n            <jats:italic>phoR-phoP<\/jats:italic>\n            system of\n            <jats:italic>Streptomyces lividans<\/jats:italic>\n            has been cloned and characterized. PhoR showed all of the characteristics of the membrane-bound sensor proteins, whereas PhoP is a member of the DNA-binding OmpR family. Deletion mutants lacking\n            <jats:italic>phoP<\/jats:italic>\n            or\n            <jats:italic>phoR-phoP<\/jats:italic>\n            , were unable to grow in minimal medium at low phosphate concentration (10 \u03bcM). Growth was fully restored by complementation with the\n            <jats:italic>phoR-phoP<\/jats:italic>\n            genes. Both\n            <jats:italic>S. lividans<\/jats:italic>\n            \u0394\n            <jats:italic>phoP<\/jats:italic>\n            and \u0394\n            <jats:italic>phoR-phoP<\/jats:italic>\n            deletion mutants were unable to synthesize extracellular alkaline phosphatase (AP) as shown by immunodetection with anti-AP antibodies and by enzymatic analysis, suggesting that the PhoR-PhoP system is required for expression of the AP gene (\n            <jats:italic>phoA<\/jats:italic>\n            ). Synthesis of AP was restored by complementation of the deletion mutants with\n            <jats:italic>phoR-phoP<\/jats:italic>\n            . The biosynthesis of two secondary metabolites, actinorhodin and undecylprodigiosin, was significantly increased in both solid and liquid medium in the \u0394\n            <jats:italic>phoP<\/jats:italic>\n            or \u0394\n            <jats:italic>phoR-phoP<\/jats:italic>\n            deletion mutants. Negative phosphate control of both secondary metabolites was restored by complementation with the\n            <jats:italic>phoR-phoP<\/jats:italic>\n            cluster. These results prove that expression of both\n            <jats:italic>phoA<\/jats:italic>\n            and genes implicated in the biosynthesis of secondary metabolites in\n            <jats:italic>S. lividans<\/jats:italic>\n            is regulated by a mechanism involving the two-component PhoR-PhoP system.\n          <\/jats:p>","DOI":"10.1073\/pnas.0931429100","type":"journal-article","created":{"date-parts":[[2003,5,13]],"date-time":"2003-05-13T18:28:41Z","timestamp":1052850521000},"page":"6133-6138","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":213,"title":["The two-component PhoR-PhoP system controls both primary metabolism and secondary metabolite biosynthesis in\n            <i>Streptomyces lividans<\/i>"],"prefix":"10.1073","volume":"100","author":[{"given":"A.","family":"Sola-Landa","sequence":"first","affiliation":[{"name":"Instituto de Biotecnolog\u00eda de Le\u00f3n (INBIOTEC), Parque Cient\u00edfico de Le\u00f3n, Avenida del Real, n\u00b0 1, 24006 Le\u00f3n, Spain; and Area de Microbiolog\u00eda, Facultad de Ciencias Biol\u00f3gicas y Ambientales, Universidad de Le\u00f3n, 24071 Le\u00f3n, Spain"}]},{"given":"R. S.","family":"Moura","sequence":"additional","affiliation":[{"name":"Instituto de Biotecnolog\u00eda de Le\u00f3n (INBIOTEC), Parque Cient\u00edfico de Le\u00f3n, Avenida del Real, n\u00b0 1, 24006 Le\u00f3n, Spain; and Area de Microbiolog\u00eda, Facultad de Ciencias Biol\u00f3gicas y Ambientales, Universidad de Le\u00f3n, 24071 Le\u00f3n, Spain"}]},{"given":"J. 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