title: The Aspergillus fumigatus conidial melanin production is regulated by the bifunctional bHLH DevR and MADS-box RlmA transcription factors.
abstract: Melanins play a crucial role in defending organisms against external stressors. In several pathogenic fungi, including the human pathogen Aspergillus fumigatus, melanin production was shown to contribute to virulence. A. fumigatus produces two different types of melanins, i.e., pyomelanin and dihydroxynaphthalene (DHN)-melanin. DHN-melanin forms the gray-green pigment characteristic for conidia, playing an important role in immune evasion of conidia and thus for fungal virulence. The DHN-melanin biosynthesis pathway is encoded by six genes organized in a cluster with the polyketide synthase gene pksP as a core element. Here, cross-species promoter analysis identified specific DNA binding sites in the DHN-melanin biosynthesis genes pksP-arp1 intergenic region that can be recognized by bHLH and MADS-box transcriptional regulators. Independent deletion of two genes coding for the transcription factors DevR (bHLH) and RlmA (MADS-box) interfered with sporulation and reduced the expression of the DHN-melanin gene cluster. In vitro and in vivo experiments proved that these transcription factors cooperatively regulate pksP expression acting both as repressors and activators in a mutually exclusive manner. The dual role executed by each regulator depends on specific DNA motifs recognized in the pksP promoter region.
authors.affiliation: Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute (HKI), Adolf-Reichwein-Str. 23, Jena, 07745, Germany.|Leibniz Research Group - Biobricks of Microbial Natural Product Syntheses, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Germany.
authors.forename: Vito
authors.initials: V
authors.lastname: Valiante
authors.affiliation: Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute (HKI), Adolf-Reichwein-Str. 23, Jena, 07745, Germany.|Department of Microbiology and Molecular Biology, Institute of Microbiology, Friedrich Schiller University Jena, Adolf-Reichwein-Str. 23, Jena, 07745, Germany.
authors.forename: Clara
authors.initials: C
authors.lastname: Baldin
authors.affiliation: Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute (HKI), Adolf-Reichwein-Str. 23, Jena, 07745, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Hortschansky
authors.affiliation: Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute (HKI), Adolf-Reichwein-Str. 23, Jena, 07745, Germany.|Department of Microbiology and Molecular Biology, Institute of Microbiology, Friedrich Schiller University Jena, Adolf-Reichwein-Str. 23, Jena, 07745, Germany.
authors.forename: Radhika
authors.initials: R
authors.lastname: Jain
authors.affiliation: Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute (HKI), Adolf-Reichwein-Str. 23, Jena, 07745, Germany.|Department of Microbiology and Molecular Biology, Institute of Microbiology, Friedrich Schiller University Jena, Adolf-Reichwein-Str. 23, Jena, 07745, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Thywißen
authors.affiliation: Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute (HKI), Adolf-Reichwein-Str. 23, Jena, 07745, Germany.|Transfer Group Anti-Infectives, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Straßburger
authors.affiliation: Research Group Bioinformatics/Systems Biology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Germany.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Shelest
authors.affiliation: Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute (HKI), Adolf-Reichwein-Str. 23, Jena, 07745, Germany.|Department of Microbiology and Molecular Biology, Institute of Microbiology, Friedrich Schiller University Jena, Adolf-Reichwein-Str. 23, Jena, 07745, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Heinekamp
authors.affiliation: Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute (HKI), Adolf-Reichwein-Str. 23, Jena, 07745, Germany. axel.brakhage@leibniz-hki.de.|Department of Microbiology and Molecular Biology, Institute of Microbiology, Friedrich Schiller University Jena, Adolf-Reichwein-Str. 23, Jena, 07745, Germany. axel.brakhage@leibniz-hki.de.
authors.forename: Axel A
authors.initials: AA
authors.lastname: Brakhage
mesh_terms: D001232:Aspergillus fumigatus / Q000235:genetics / Q000378:metabolism*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D053898:Biosynthetic Pathways; D005656:Fungal Proteins / Q000378:metabolism; D005800:Genes, Fungal; D008543:Melanins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D005810:Multigene Family; D010858:Pigmentation; D011485:Protein Binding; D000072417:Protein Domains; D013172:Spores, Fungal / Q000235:genetics / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D005656:Fungal Proteins; D008543:Melanins