{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,8]],"date-time":"2025-11-08T12:47:42Z","timestamp":1762606062195},"reference-count":25,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2012,1,1]],"date-time":"2012-01-01T00:00:00Z","timestamp":1325376000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2012,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Marinactinospora thermotolerans<\/jats:named-content>\n            SCSIO 00652, originating from a deep-sea marine sediment of the South China Sea, was discovered to produce antimicrobial nucleoside antibiotic A201A. Whole-genome scanning and annotation strategies enabled us to localize the genes responsible for A201A biosynthesis and to experimentally identify the gene cluster; inactivation of\n            <jats:italic>mtdF<\/jats:italic>\n            , an oxidoreductase gene within the suspected gene cluster, abolished A201A production. Bioinformatics analysis revealed that a gene designated\n            <jats:italic>mtdA<\/jats:italic>\n            furthest upstream within the A201A biosynthetic gene cluster encodes a GntR family transcriptional regulator. To determine the role of MtdA in regulating A201A production, the\n            <jats:italic>mtdA<\/jats:italic>\n            gene was inactivated in frame and the resulting \u0394\n            <jats:italic>mtdA<\/jats:italic>\n            mutant was fermented alongside the wild-type strain as a control. High-performance liquid chromatography (HPLC) analyses of fermentation extracts revealed that the \u0394\n            <jats:italic>mtdA<\/jats:italic>\n            mutant produced A201A in a yield \u223c25-fold superior to that of the wild-type strain, thereby demonstrating that\n            <jats:italic>MtdA<\/jats:italic>\n            is a negative transcriptional regulator governing A201A biosynthesis. By virtue of its high production capacity, the \u0394\n            <jats:italic>mtdA<\/jats:italic>\n            mutant constitutes an ideal host for the efficient large-scale production of A201A. These results validate\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">M. thermotolerans<\/jats:named-content>\n            as an emerging source of antibacterial agents and highlight the efficiency of metabolic engineering for antibiotic titer improvement.\n          <\/jats:p>","DOI":"10.1128\/aac.05278-11","type":"journal-article","created":{"date-parts":[[2011,11,8]],"date-time":"2011-11-08T08:47:43Z","timestamp":1320742063000},"page":"110-114","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":42,"title":["Discovery and Engineered Overproduction of Antimicrobial Nucleoside Antibiotic A201A from the Deep-Sea Marine Actinomycete Marinactinospora thermotolerans SCSIO 00652"],"prefix":"10.1128","volume":"56","author":[{"given":"Qinghua","family":"Zhu","sequence":"first","affiliation":[{"name":"CAS Key Laboratory of Marine Bio-resources Sustainable Utilization, Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Li","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Marine Bio-resources Sustainable Utilization, Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China"},{"name":"Graduate University of Chinese Academy of Sciences, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junying","family":"Ma","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Marine Bio-resources Sustainable Utilization, Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minghe","family":"Luo","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Marine Bio-resources Sustainable Utilization, Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Wang","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Marine Bio-resources Sustainable Utilization, Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongbo","family":"Huang","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Marine Bio-resources Sustainable Utilization, Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinpeng","family":"Tian","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Marine Bio-resources Sustainable Utilization, Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenjun","family":"Li","sequence":"additional","affiliation":[{"name":"Yunnan Institute of Microbiology, Yunnan University, Kunming, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Si","family":"Zhang","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Marine Bio-resources Sustainable Utilization, Guangdong Key Laboratory 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