• Hymenosetin, a 3-decalinoyltetramic acid antibiotic from cultures of the ash dieback pathogen, Hymenoscyphus pseudoalbidus.

      Halecker, Sandra; Surup, Frank; Kuhnert, Eric; Mohr, Kathrin I; Brock, Nelson L; Dickschat, Jeroen S; Junker, Corina; Schulz, Barbara; Stadler, Marc; Helmholtz Centre for ifection research, Innhoffenstr. 7, D38124 Braunschweig, Germany. (2014-04)
      A 3-decalinoyltetramic acid, for which the trivial name hymenosetin is proposed, was isolated from crude extracts of a virulent strain of the ash dieback pathogen, Hymenoscyphus pseudoalbidus (="Chalara fraxinea"). This compound was produced only under certain culture conditions in submerged cultures of the fungus. Its planar structure was determined by NMR spectroscopy and by mass spectrometry. The absolute stereochemistry was assigned by CD spectroscopy and HETLOC data. Hymenosetin exhibited broad spectrum antibacterial and antifungal activities (including strong inhibition of MRSA), as well as moderate cytotoxic effects. So far, the metabolite proved inactive in assays for evaluation of phytotoxicity, whereas viridiol, another secondary metabolite known from H. pseudoalbidus, was regarded as phytotoxic principle of the pathogen against its host, Fraxinus excelsior. Further studies will show whether hymenosetin constitutes a defence metabolite that is produced by the pathogenic fungus to combat other microbes and fungi in the natural environment.
    • Production of Obionin A and Derivatives by the Sooty Blotch Fungus Microcyclospora malicola.

      Surup, Frank; Medjedović, Ajda; Schroers, Hans-Josef; Stadler, Marc; Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig. (2015-10)
      A multitude of sooty blotch and flyspeck fungi, mainly belonging to the Ascomycetes order Capnodiales, causes dark blemishes and flyspeck-like spots on apples worldwide. Different sooty blotch and flyspeck fungi can coexist in the same orchard and even on a single fruit. Our preceding experiments revealed an activity of Microcyclospora malicola strain 1930 against the anthracnose fungus Colletotrichum fioriniae in dual culture assays. Extracts of M. malicola strain 1930 showed a broad bioactivity against filamentous fungus Mucor hiemalis and gram-positive bacterium Bacillus subtilis. A bioactivity-guided isolation led to the identification of obionin A (1) as the main active principle. In addition to 1, which was previously isolated from the marine fungus Leptosphaeria obiones, we isolated three derivatives. Metabolite 2 bears a keto function at C-6, besides the replacement of oxygen by nitrogen at position 10. Two more derivatives are adducts (3, 4) of acetone as work-up artifacts. Because obionin A (1) and its derivative 2 showed cytotoxic effects and antifungal activities, we propose a role of these secondary metabolites in the antagonism between M. malicola and other apple colonizing sooty blotch and flyspeck fungi, other epiphytes, or apple pathogens competing for the same ecological niche.