caa a22 4500 605504679 CHVBK 20210128100617.0 cr unu---uuuuu 210128e20151201xx s 000 0 eng 10.1007/s00253-015-6898-1 doi (NATIONALLICENCE)springer-10.1007/s00253-015-6898-1 Identification of the antiphagocytic trypacidin gene cluster in the human-pathogenic fungus Aspergillus fumigatus [Elektronische Daten] [Derek Mattern, Hanno Schoeler, Jakob Weber, Silvia Novohradská, Kaswara Kraibooj, Hans-Martin Dahse, Falk Hillmann, Vito Valiante, Marc Figge, Axel Brakhage] The opportunistic human pathogen Aspergillus fumigatus produces numerous different natural products. The genetic basis for the biosynthesis of a number of known metabolites has remained unknown. The gene cluster encoding for the biosynthesis of the conidia-bound metabolite trypacidin is of particular interest because of its antiprotozoal activity and possible role in the infection process. Here, we show that the genes encoding the biosynthesis enzymes of trypacidin reside within an orphan gene cluster in A. fumigatus. Genome mining identified tynC as an uncharacterized polyketide synthase with high similarity to known enzymes, whose products are structurally related to trypacidin including endocrocin and fumicycline. Gene deletion of tynC resulted in the complete absence of trypacidin production, which was fully restored when the mutant strain was complemented with the wild-type gene. When confronted with macrophages, the tynC deletion mutant conidia were more frequently phagocytosed than those of the parental wild-type strain. This was also found for phagocytic amoebae of the species Dictyostelium discoideum, which showed increased phagocytosis of ΔtynC conidia. Both macrophages and amoebae were also sensitive to trypacidin. Therefore, our results suggest that the conidium-bound trypacidin could have a protective function against phagocytes both in the environment and during the infection process. Springer-Verlag Berlin Heidelberg, 2015 Aspergillus fumigatus nationallicence Genome mining nationallicence Trypacidin nationallicence Polyketide nationallicence Macrophage nationallicence Dictyostelium discoideum nationallicence Mattern Derek Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Beutenbergstrasse 11a, 07745, Jena, Germany aut Schoeler Hanno Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Beutenbergstrasse 11a, 07745, Jena, Germany aut Weber Jakob Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Beutenbergstrasse 11a, 07745, Jena, Germany aut Novohradská Silvia Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Beutenbergstrasse 11a, 07745, Jena, Germany aut Kraibooj Kaswara Friedrich Schiller University Jena, Jena, Germany aut Dahse Hans-Martin Department of Infection Biology, Leibniz Institute for Infection Biology and Natural Product Research (HKI), Jena, Germany aut Hillmann Falk Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Beutenbergstrasse 11a, 07745, Jena, Germany aut Valiante Vito Leibniz Junior Research Group - Biobricks of Microbial Natural Product Syntheses, Jena, Germany aut Figge Marc Friedrich Schiller University Jena, Jena, Germany aut Brakhage Axel Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Beutenbergstrasse 11a, 07745, Jena, Germany aut Applied Microbiology and Biotechnology Springer Berlin Heidelberg 99/23(2015-12-01), 10151-10161 0175-7598 99:23<10151 2015 99 253 https://doi.org/10.1007/s00253-015-6898-1 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00253-015-6898-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Mattern Derek Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Beutenbergstrasse 11a, 07745, Jena, Germany aut NATIONALLICENCE 700 1- Schoeler Hanno Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Beutenbergstrasse 11a, 07745, Jena, Germany aut NATIONALLICENCE 700 1- Weber Jakob Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Beutenbergstrasse 11a, 07745, Jena, Germany aut NATIONALLICENCE 700 1- Novohradská Silvia Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Beutenbergstrasse 11a, 07745, Jena, Germany aut NATIONALLICENCE 700 1- Kraibooj Kaswara Friedrich Schiller University Jena, Jena, Germany aut NATIONALLICENCE 700 1- Dahse Hans-Martin Department of Infection Biology, Leibniz Institute for Infection Biology and Natural Product Research (HKI), Jena, Germany aut NATIONALLICENCE 700 1- Hillmann Falk Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Beutenbergstrasse 11a, 07745, Jena, Germany aut NATIONALLICENCE 700 1- Valiante Vito Leibniz Junior Research Group - Biobricks of Microbial Natural Product Syntheses, Jena, Germany aut NATIONALLICENCE 700 1- Figge Marc Friedrich Schiller University Jena, Jena, Germany aut NATIONALLICENCE 700 1- Brakhage Axel Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Beutenbergstrasse 11a, 07745, Jena, Germany aut NATIONALLICENCE 773 0- Applied Microbiology and Biotechnology Springer Berlin Heidelberg 99/23(2015-12-01), 10151-10161 0175-7598 99:23<10151 2015 99 253