Browsing publications of the research group of microbial drugs (MWIS) by Authors
Comparative analyses of the Hymenoscyphus fraxineus and Hymenoscyphus albidus genomes reveals potentially adaptive differences in secondary metabolite and transposable element repertoires.Elfstrand, Malin; Chen, Jun; Cleary, Michelle; Halecker, Sandra; Ihrmark, Katarina; Karlsson, Magnus; Davydenko, Kateryna; Stenlid, Jan; Stadler, Marc; Durling, Mikael Brandström; et al. (BMC, 2021-07-04)Background: The dieback epidemic decimating common ash (Fraxinus excelsior) in Europe is caused by the invasive fungus Hymenoscyphus fraxineus. In this study we analyzed the genomes of H. fraxineus and H. albidus, its native but, now essentially displaced, non-pathogenic sister species, and compared them with several other members of Helotiales. The focus of the analyses was to identify signals in the genome that may explain the rapid establishment of H. fraxineus and displacement of H. albidus. Results: The genomes of H. fraxineus and H. albidus showed a high level of synteny and identity. The assembly of H. fraxineus is 13 Mb longer than that of H. albidus', most of this difference can be attributed to higher dispersed repeat content (i.e. transposable elements [TEs]) in H. fraxineus. In general, TE families in H. fraxineus showed more signals of repeat-induced point mutations (RIP) than in H. albidus, especially in Long-terminal repeat (LTR)/Copia and LTR/Gypsy elements. Comparing gene family expansions and 1:1 orthologs, relatively few genes show signs of positive selection between species. However, several of those did appeared to be associated with secondary metabolite genes families, including gene families containing two of the genes in the H. fraxineus-specific, hymenosetin biosynthetic gene cluster (BGC). Conclusion: The genomes of H. fraxineus and H. albidus show a high degree of synteny, and are rich in both TEs and BGCs, but the genomic signatures also indicated that H. albidus may be less well equipped to adapt and maintain its ecological niche in a rapidly changing environment.
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.
Minutellins A - D, azaphilones from the stromata of Annulohypoxylon minutellum (Xylariaceae).Kuhnert, Eric; Surup, Frank; Halecker, Sandra; Stadler, Marc; Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017-02-16)During the course of our screening for new metabolites with chemotaxonomic importance from stromata of fungi from the family Xylariaceae, we characterized several interesting metabolites in the fungus Annulohypoxylon minutellum. Extraction of the fruiting bodies and purification by preparative HPLC resulted in the isolation of five metabolites. The main compound was identified as the known metabolite hinnulin A (5), while four minor compounds were found to represent previously undescribed azaphilones, named minutellins A - D (1-4). Their planar structures were elucidated using NMR and HRESIMS data; absolute stereochemistry was assigned by CD data and Mosher's method. Compounds 1, 3 and 5 showed cytotoxic effects against murine and human cells. As the production of 1-5 is restricted to a group of closely related Annulohypoxylon species, they serve well as chemotaxonomic marker.