{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:29:52Z","timestamp":1790706592876,"version":"4.1.0"},"reference-count":45,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2014,10,1]],"date-time":"2014-10-01T00:00:00Z","timestamp":1412121600000},"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":[[2014,10]]},"abstract":"ABSTRACT<\/jats:title>\n \n The emergence of antibiotic-resistant pathogenic bacteria within the last decades is one reason for the urgent need for new antibacterial agents. A strategy to discover new anti-infective compounds is the evaluation of the genetic capacity of secondary metabolite producers and the activation of cryptic gene clusters (genome mining). One genus known for its potential to synthesize medically important products is\n Amycolatopsis<\/jats:named-content>\n . However,\n Amycolatopsis japonicum<\/jats:named-content>\n does not produce an antibiotic under standard laboratory conditions. In contrast to most\n Amycolatopsis<\/jats:named-content>\n strains,\n A. japonicum<\/jats:named-content>\n is genetically tractable with different methods. In order to activate a possible silent glycopeptide cluster, we introduced a gene encoding the transcriptional activator of balhimycin biosynthesis, the\n bbr<\/jats:italic>\n gene from\n Amycolatopsis balhimycina<\/jats:named-content>\n (\n bbr<\/jats:italic>\n Aba<\/jats:sub>\n ), into\n A. japonicum<\/jats:named-content>\n . This resulted in the production of an antibiotically active compound. Following whole-genome sequencing of\n A. japonicum<\/jats:named-content>\n , 29 cryptic gene clusters were identified by genome mining. One of these gene clusters is a putative glycopeptide biosynthesis gene cluster. Using bioinformatic tools, ristomycin (syn. ristocetin), a type III glycopeptide, which has antibacterial activity and which is used for the diagnosis of von Willebrand disease and Bernard-Soulier syndrome, was deduced as a possible product of the gene cluster. Chemical analyses by high-performance liquid chromatography and mass spectrometry (HPLC-MS), tandem mass spectrometry (MS\/MS), and nuclear magnetic resonance (NMR) spectroscopy confirmed the\n in silico<\/jats:italic>\n prediction that the recombinant\n A. japonicum<\/jats:named-content>\n \/pRM4-\n bbr<\/jats:italic>\n Aba<\/jats:sub>\n synthesizes ristomycin A.\n <\/jats:p>","DOI":"10.1128\/aac.03512-14","type":"journal-article","created":{"date-parts":[[2014,8,12]],"date-time":"2014-08-12T06:36:28Z","timestamp":1407825388000},"page":"6185-6196","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":79,"title":["Overproduction of Ristomycin A by Activation of a Silent Gene Cluster in Amycolatopsis japonicum MG417-CF17"],"prefix":"10.1128","volume":"58","author":[{"given":"Marius","family":"Spohn","sequence":"first","affiliation":[{"name":"Interfaculty Institute of Microbiology and Infection Medicine Tuebingen, Microbiology\/Biotechnology, University of Tuebingen, Tuebingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Kirchner","sequence":"additional","affiliation":[{"name":"German Centre for Infection Research (DZIF), Partner Site Tuebingen, Tuebingen, Germany"},{"name":"Pharmaceutical Institute, Department of Pharmaceutical Biology, University of Tuebingen, Tuebingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Kulik","sequence":"additional","affiliation":[{"name":"Interfaculty Institute of Microbiology and Infection Medicine Tuebingen, Microbiology\/Biotechnology, University of Tuebingen, Tuebingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelika","family":"Jochim","sequence":"additional","affiliation":[{"name":"Interfaculty Institute of Microbiology and Infection Medicine Tuebingen, Microbiology\/Biotechnology, University of Tuebingen, Tuebingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Wolf","sequence":"additional","affiliation":[{"name":"Interfaculty Institute of Microbiology and Infection Medicine Tuebingen, Microbiology\/Biotechnology, University of Tuebingen, Tuebingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Muenzer","sequence":"additional","affiliation":[{"name":"Department of Physiology I, University of Tuebingen, Tuebingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Borst","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Cardiovascular Medicine, University of Tuebingen, Tuebingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald","family":"Gross","sequence":"additional","affiliation":[{"name":"German Centre for Infection Research (DZIF), Partner Site Tuebingen, Tuebingen, Germany"},{"name":"Pharmaceutical Institute, Department of Pharmaceutical Biology, University of Tuebingen, Tuebingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Wohlleben","sequence":"additional","affiliation":[{"name":"Interfaculty Institute of Microbiology and Infection Medicine Tuebingen, Microbiology\/Biotechnology, University of Tuebingen, Tuebingen, Germany"},{"name":"German Centre for Infection Research (DZIF), Partner Site Tuebingen, Tuebingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evi","family":"Stegmann","sequence":"additional","affiliation":[{"name":"Interfaculty Institute of Microbiology and Infection Medicine Tuebingen, Microbiology\/Biotechnology, University of Tuebingen, Tuebingen, Germany"},{"name":"German Centre for Infection Research (DZIF), Partner Site Tuebingen, Tuebingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.37.426"},{"key":"e_1_3_3_3_2","unstructured":"HartmannFAPerkinsCM. 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