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For some systems, the binding of biosynthetic products to the\n                    <jats:styled-content style=\"fixed-case\">CSR<\/jats:styled-content>\n                    has been shown to provide negative feedback. Here we show for the production of lidamycin (\n                    <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>\n                    \u20101027), a clinically relevant antitumor agent, by\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>S<\/jats:italic>\n                    <\/jats:styled-content>\n                    <jats:italic>treptomyces globisporus<\/jats:italic>\n                    that negative feedback can extend to a point higher in the regulatory cascade. We show that the\n                    <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>\n                    \u2010binding activity of the\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>S<\/jats:italic>\n                    <\/jats:styled-content>\n                    <jats:italic>.\u2009globisporus<\/jats:italic>\n                    orthologue of\n                    <jats:styled-content style=\"fixed-case\">AtrA<\/jats:styled-content>\n                    , which was initially described as a transcriptional activator of actinorhodin biosynthesis in\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>S<\/jats:italic>\n                    <\/jats:styled-content>\n                    <jats:italic>.\u2009coelicolor<\/jats:italic>\n                    , is inhibited by the binding of heptaene, a biosynthetic intermediate of lidamycin. Additional experiments described here show that\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>S<\/jats:italic>\n                    <\/jats:styled-content>\n                    <jats:italic>.\u2009globisporus<\/jats:italic>\n                    \u2005\n                    <jats:styled-content style=\"fixed-case\">AtrA<\/jats:styled-content>\n                    binds\n                    <jats:italic>in vivo<\/jats:italic>\n                    as well as\n                    <jats:italic>in vitro<\/jats:italic>\n                    to the promoter region of the gene encoding\n                    <jats:styled-content style=\"fixed-case\">SgcR1<\/jats:styled-content>\n                    , one of the\n                    <jats:styled-content style=\"fixed-case\">CSRs<\/jats:styled-content>\n                    of lidamycin production. The feedback to the pleiotropic regulator\n                    <jats:styled-content style=\"fixed-case\">AtrA<\/jats:styled-content>\n                    is likely to provide a mechanism for coordinating the production of lidamycin with that of other secondary metabolites. The activity of\n                    <jats:styled-content style=\"fixed-case\">AtrA<\/jats:styled-content>\n                    is also regulated by actinorhodin. As\n                    <jats:styled-content style=\"fixed-case\">AtrA<\/jats:styled-content>\n                    is evolutionarily conserved, negative feedback of the type described here may be widespread within the streptomycetes.\n                  <\/jats:p>","DOI":"10.1111\/mmi.13004","type":"journal-article","created":{"date-parts":[[2015,3,19]],"date-time":"2015-03-19T02:03:23Z","timestamp":1426730603000},"page":"1257-1271","source":"Crossref","is-referenced-by-count":32,"title":["Binding of a biosynthetic intermediate to\n                    <scp>AtrA<\/scp>\n                    modulates the production of lidamycin by\n                    <scp>\n                      <i>S<\/i>\n                    <\/scp>\n                    <i>treptomyces globisporus<\/i>"],"prefix":"10.1111","volume":"96","author":[{"given":"Xingxing","family":"Li","sequence":"first","affiliation":[{"name":"The Key Laboratory of Biotechnology of Antibiotics of Ministry of Health Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing 100050 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tengfei","family":"Yu","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Biotechnology of Antibiotics of Ministry of Health Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing 100050 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"He","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Biotechnology of Antibiotics of Ministry of Health Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing 100050 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth J.","family":"McDowall","sequence":"additional","affiliation":[{"name":"Astbury Centre for Structural Molecular Biology Faculty of Biological Sciences University of Leeds  Leeds LS2\u20099JT UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingya","family":"Jiang","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Biotechnology of Antibiotics of Ministry of Health Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing 100050 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhibo","family":"Jiang","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Biotechnology of Antibiotics of Ministry of Health Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing 100050 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linzhuan","family":"Wu","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Biotechnology of Antibiotics of Ministry of Health Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing 100050 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangwei","family":"Li","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Biotechnology of Antibiotics of Ministry of Health Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing 100050 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinglian","family":"Li","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Biotechnology of Antibiotics of Ministry of Health Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing 100050 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songmei","family":"Wang","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Biotechnology of Antibiotics of Ministry of Health Institute of Medicinal Biotechnology Chinese 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