{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T13:26:58Z","timestamp":1761744418861,"version":"3.41.2"},"reference-count":41,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2017,4,15]],"date-time":"2017-04-15T00:00:00Z","timestamp":1492214400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31430004","31670058","31300034"],"award-info":[{"award-number":["31430004","31670058","31300034"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People's Republic of China","doi-asserted-by":"publisher","award":["2016YFA0500600","2012CB721102"],"award-info":[{"award-number":["2016YFA0500600","2012CB721102"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Appl Environ Microbiol"],"published-print":{"date-parts":[[2017,4,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Rifamycin and its derivatives are particularly effective against the pathogenic mycobacteria\n            <jats:named-content content-type=\"genus-species\">Mycobacterium tuberculosis<\/jats:named-content>\n            and\n            <jats:named-content content-type=\"genus-species\">Mycobacterium leprae<\/jats:named-content>\n            . Although the biosynthetic pathway of rifamycin has been extensively studied in\n            <jats:named-content content-type=\"genus-species\">Amycolatopsis mediterranei<\/jats:named-content>\n            , little is known about the regulation in rifamycin biosynthesis. Here, an\n            <jats:italic>in vivo<\/jats:italic>\n            transposon system was employed to identify genes involved in the regulation of rifamycin production in\n            <jats:named-content content-type=\"genus-species\">A. mediterranei<\/jats:named-content>\n            U32. In total, nine rifamycin-deficient mutants were isolated, among which three mutants had the transposon inserted in\n            <jats:italic>AMED_0655<\/jats:italic>\n            (\n            <jats:italic>rifZ<\/jats:italic>\n            , encoding a LuxR family regulator). The\n            <jats:italic>rifZ<\/jats:italic>\n            gene was further knocked out via homologous recombination, and the transcription of genes in the rifamycin biosynthetic gene cluster (\n            <jats:italic>rif<\/jats:italic>\n            cluster) was remarkably reduced in the\n            <jats:italic>rifZ<\/jats:italic>\n            null mutant. Based on the cotranscription assay results, genes within the\n            <jats:italic>rif<\/jats:italic>\n            cluster were grouped into 10 operons, sharing six promoter regions. By use of electrophoretic mobility shift assay and DNase I footprinting assay, RifZ was proved to specially bind to all six promoter regions, which was consistent with the fact that RifZ regulated the transcription of the whole\n            <jats:italic>rif<\/jats:italic>\n            cluster. The binding consensus sequence was further characterized through alignment using the RifZ-protected DNA sequences. By use of bionformatic analysis, another five promoters containing the RifZ box (CTACC-N8-GGATG) were identified, among which the binding of RifZ to the promoter regions of both\n            <jats:italic>rifK<\/jats:italic>\n            and\n            <jats:italic>orf18<\/jats:italic>\n            (\n            <jats:italic>AMED_0645<\/jats:italic>\n            ) was further verified. As RifZ directly regulates the transcription of all operons within the\n            <jats:italic>rif<\/jats:italic>\n            cluster, we propose that RifZ is a pathway-specific regulator for the\n            <jats:italic>rif<\/jats:italic>\n            cluster.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            To this day, rifamycin and its derivatives are still the first-line antituberculosis drugs. The biosynthesis of rifamycin has been extensively studied, and most biosynthetic processes have been characterized. However, little is known about the regulation of the transcription of the rifamycin biosynthetic gene cluster (\n            <jats:italic>rif<\/jats:italic>\n            cluster), and no regulator has been characterized. Through the employment of transposon screening, we here characterized a LuxR family regulator, RifZ, as a direct transcriptional activator for the\n            <jats:italic>rif<\/jats:italic>\n            cluster. As RifZ directly regulates the transcription of the entire\n            <jats:italic>rif<\/jats:italic>\n            cluster, it is considered a pathway-specific regulator for rifamycin biosynthesis. Therefore, as the first regulator characterized for direct regulation of\n            <jats:italic>rif<\/jats:italic>\n            cluster transcription, RifZ may provide a new clue for further engineering of high-yield industrial strains.\n          <\/jats:p>","DOI":"10.1128\/aem.03201-16","type":"journal-article","created":{"date-parts":[[2017,2,4]],"date-time":"2017-02-04T01:50:17Z","timestamp":1486173017000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":10,"title":["RifZ (AMED_0655) Is a Pathway-Specific Regulator for Rifamycin Biosynthesis in Amycolatopsis mediterranei"],"prefix":"10.1128","volume":"83","author":[{"given":"Chen","family":"Li","sequence":"first","affiliation":[{"name":"State Key Laboratory of Genetic Engineering, Department of Microbiology and Microbial Engineering, School of Life Sciences, Fudan University, Shanghai, 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