title: A Non-canonical Melanin Biosynthesis Pathway Protects Aspergillus terreus Conidia from Environmental Stress.
abstract: Melanins are ubiquitous pigments found in all kingdoms of life. Most organisms use them for protection from environmental stress, although some fungi employ melanins as virulence determinants. The human pathogenic fungus Aspergillus fumigatus and related Ascomycetes produce dihydroxynaphthalene- (DHN) melanin in their spores, the conidia, and use it to inhibit phagolysosome acidification. However, biosynthetic origin of melanin in a related fungus, Aspergillus terreus, has remained a mystery because A. terreus lacks genes for synthesis of DHN-melanin. Here we identify genes coding for an unusual NRPS-like enzyme (MelA) and a tyrosinase (TyrP) that A. terreus expressed under conidiation conditions. We demonstrate that MelA produces aspulvinone E, which is activated for polymerization by TyrP. Functional studies reveal that this new pigment, Asp-melanin, confers resistance against UV light and hampers phagocytosis by soil amoeba. Unexpectedly, Asp-melanin does not inhibit acidification of phagolysosomes, thus likely contributing specifically to survival of A. terreus conidia in acidic environments.
authors.affiliation: Microbial Biochemistry and Physiology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute, Beutenbergstr. 11a, 07745 Jena, Germany; Fungal Genetics and Biology Group, School of Life Sciences, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
authors.forename: Elena
authors.initials: E
authors.lastname: Geib
authors.affiliation: Microbial Biochemistry and Physiology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute, Beutenbergstr. 11a, 07745 Jena, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Gressler
authors.affiliation: Junior Research Group Evolution of Microbial Interactions, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute, Beutenbergstr. 11a, 07745 Jena, Germany.
authors.forename: Iuliia
authors.initials: I
authors.lastname: Viediernikova
authors.affiliation: Junior Research Group Evolution of Microbial Interactions, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute, Beutenbergstr. 11a, 07745 Jena, Germany.
authors.forename: Falk
authors.initials: F
authors.lastname: Hillmann
authors.affiliation: Microbial Immunology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute, Beutenbergstr. 11a, 07745 Jena, Germany; Institute for Microbiology, Friedrich Schiller University, 07743 Jena, Germany.
authors.forename: Ilse D
authors.initials: ID
authors.lastname: Jacobsen
authors.affiliation: Electron Microscopic Centre, University Hospital of the Friedrich Schiller University Jena, Ziegelmühlenweg 1, 07443 Jena, Germany.
authors.forename: Sandor
authors.initials: S
authors.lastname: Nietzsche
authors.affiliation: Biomolecular Chemistry, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute, Beutenbergstr. 11a, 07745 Jena, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Hertweck
authors.affiliation: Microbial Biochemistry and Physiology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute, Beutenbergstr. 11a, 07745 Jena, Germany; Fungal Genetics and Biology Group, School of Life Sciences, University of Nottingham, University Park, Nottingham NG7 2RD, UK; Institute for Microbiology, Friedrich Schiller University, 07743 Jena, Germany. Electronic address: matthias.brock@nottingham.ac.uk.
authors.forename: Matthias
authors.initials: M
authors.lastname: Brock
mesh_terms: D001230:Aspergillus / Q000378:metabolism*; D004777:Environment; D004783:Environmental Microbiology; D006863:Hydrogen-Ion Concentration; D008543:Melanins / Q000096:biosynthesis*; D014442:Monophenol Monooxygenase / Q000235:genetics / Q000378:metabolism; D010453:Peptide Synthases / Q000235:genetics / Q000378:metabolism; D013172:Spores, Fungal / Q000378:metabolism*; D013312:Stress, Physiological
chemical_list: D008543:Melanins; D014442:Monophenol Monooxygenase; D010453:Peptide Synthases