{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T03:08:05Z","timestamp":1771556885059,"version":"3.50.1"},"reference-count":66,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,3,11]],"date-time":"2015-03-11T00:00:00Z","timestamp":1426032000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["Excellence Initiative \/ JSMC"],"award-info":[{"award-number":["Excellence Initiative \/ JSMC"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Microbiology"],"published-print":{"date-parts":[[2015,4]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\"><jats:italic>A<\/jats:italic><\/jats:styled-content><jats:italic>spergillus fumigatus<\/jats:italic> is an opportunistic human pathogenic fungus causing life\u2010threatening infections in immunocompromised patients. Adaptation to different habitats and also virulence of the fungus depends on signal perception and transduction by modules such as the cyclic <jats:styled-content style=\"fixed-case\">AMP<\/jats:styled-content>\u2010dependent protein kinase <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">PKA<\/jats:styled-content>) pathway. Here, by transcriptome analysis, 632 differentially regulated genes of this important signaling cascade were identified, including 23 putative transcriptional regulators. The highest upregulated transcription factor gene was located in a previously unknown secondary metabolite gene cluster, which we named <jats:styled-content style=\"fixed-case\"><jats:italic>fmp<\/jats:italic><\/jats:styled-content>, encoding an incomplete non\u2010ribosomal peptide synthetase, <jats:styled-content style=\"fixed-case\">FmpE<\/jats:styled-content>. Overexpression of the regulatory gene <jats:styled-content style=\"fixed-case\"><jats:italic>fmpR<\/jats:italic><\/jats:styled-content> using the <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>et<jats:styled-content style=\"fixed-case\"><jats:sup>O<\/jats:sup><\/jats:styled-content><jats:sup>n<\/jats:sup> system led to the specific expression of the other six genes of the <jats:styled-content style=\"fixed-case\"><jats:italic>fmp<\/jats:italic><\/jats:styled-content> cluster. Metabolic profiling of wild type and <jats:styled-content style=\"fixed-case\"><jats:italic>fmpR<\/jats:italic><\/jats:styled-content> overexpressing strain by <jats:styled-content style=\"fixed-case\">HPLC<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">DAD<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">HPLC<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">HRESI<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content> and structure elucidation by <jats:styled-content style=\"fixed-case\">NMR<\/jats:styled-content> led to identification of 5\u2010benzyl\u20101<jats:styled-content style=\"fixed-case\"><jats:italic>H<\/jats:italic><\/jats:styled-content>\u2010pyrrole\u20102\u2010carboxylic acid, which we named fumipyrrole. Fumipyrrole was not described as natural product yet. Chemical synthesis of fumipyrrole confirmed its structure. Interestingly, deletion of <jats:styled-content style=\"fixed-case\"><jats:italic>fmpR<\/jats:italic><\/jats:styled-content> or <jats:styled-content style=\"fixed-case\"><jats:italic>fmpE<\/jats:italic><\/jats:styled-content> led to reduced growth and sporulation of the mutant strains. Although <jats:styled-content style=\"fixed-case\"><jats:italic>fmp<\/jats:italic><\/jats:styled-content> cluster genes were transcribed in infected mouse lungs, deletion of <jats:styled-content style=\"fixed-case\"><jats:italic>fmpR<\/jats:italic><\/jats:styled-content> resulted in wild\u2010type virulence in a murine infection model.<\/jats:p>","DOI":"10.1111\/mmi.12926","type":"journal-article","created":{"date-parts":[[2015,1,13]],"date-time":"2015-01-13T08:05:15Z","timestamp":1421136315000},"page":"148-162","source":"Crossref","is-referenced-by-count":35,"title":["Transcriptome analysis of cyclic <scp>AMP<\/scp>\u2010dependent protein kinase <scp>A<\/scp>\u2013regulated genes reveals the production of the novel natural compound fumipyrrole by <scp><i>A<\/i><\/scp><i>spergillus fumigatus<\/i>"],"prefix":"10.1111","volume":"96","author":[{"given":"Juliane","family":"Macheleidt","sequence":"first","affiliation":[{"name":"Molecular and Applied Microbiology Leibniz Institute for Natural Product Research and Infection Biology (HKI)  07745 Jena Germany"},{"name":"Institute for Microbiology Friedrich Schiller University  07745 Jena Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kirstin","family":"Scherlach","sequence":"additional","affiliation":[{"name":"Biomolecular Chemistry Leibniz Institute for Natural Product Research and Infection Biology (HKI)  07745 Jena Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toni","family":"Neuwirth","sequence":"additional","affiliation":[{"name":"Biomolecular Chemistry Leibniz Institute for Natural Product Research and Infection Biology (HKI)  07745 Jena Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfgang","family":"Schmidt\u2010Heck","sequence":"additional","affiliation":[{"name":"Systems Biology\/Bioinformatics Leibniz Institute for Natural Product Research and Infection Biology (HKI)  07745 Jena Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Stra\u00dfburger","sequence":"additional","affiliation":[{"name":"Molecular and Applied Microbiology Leibniz Institute for Natural Product Research and Infection Biology (HKI)  07745 Jena Germany"},{"name":"Institute for Microbiology Friedrich Schiller University  07745 Jena Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Spraker","sequence":"additional","affiliation":[{"name":"Plant Pathology University of Wisconsin  Madison WI 53706 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua A.","family":"Baccile","sequence":"additional","affiliation":[{"name":"Boyce Thompson Institute and Department of Chemistry and Chemical Biology Cornell University  Ithaca NY 14853 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank C.","family":"Schroeder","sequence":"additional","affiliation":[{"name":"Boyce Thompson 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