Covering: up to December 2017 The diversity of secondary metabolites in the fungal order Xylariales is reviewed with special emphasis on correlations between chemical diversity and biodiversity as inferred from recent taxonomic and phylogenetic studies. The Xylariales are arguably among the predominant fungal endophytes, which are the producer organisms of pharmaceutical lead compounds including the antimycotic sordarins and the antiparasitic nodulisporic acids, as well as the marketed drug, emodepside. Many Xylariales are “macromycetes”, which form conspicuous fruiting bodies (stromata), and the metabolite profiles that are predominant in the stromata are often complementary to those encountered in corresponding mycelial cultures of a given species. Secondary metabolite profiles have recently been proven highly informative as additional parameters to support classical morphology and molecular phylogenetic approaches in order to reconstruct evolutionary relationships among these fungi. Even the recent taxonomic rearrangement of the Xylariales has been relying on such approaches, since certain groups of metabolites seem to have significance at the species, genus or family level, respectively, while others are only produced in certain taxa and their production is highly dependent on the culture conditions. The vast metabolic diversity that may be encountered in a single species or strain is illustrated based on examples like Daldinia eschscholtzii, Hypoxylon rickii, and Pestalotiopsis fici. In the future, it appears feasible to increase our knowledge of secondary metabolite diversity by embarking on certain genera that have so far been neglected, as well as by studying the volatile secondary metabolites more intensively. Methods of bioinformatics, phylogenomics and transcriptomics, which have been developed to study other fungi, are readily available for use in such scenarios.

Eight diketopiperazines including five previously unreported derivatives were isolated from an endophytic fungus cultured from the medicinal plant Globularia alypum collected in Algeria. The strain was characterised by means of morphological studies and molecular phylogenetic methods and was found to represent a species of a new genus in the Chaetomiaceae, for which we propose the name Batnamyces globulariicola. The taxonomic position of the new genus, which appears phylogenetically related to Stolonocarpus and Madurella, was evaluated by a multi-locus genealogy and by morphological studies in comparison to DNA sequence data reported in the recent monographs of the family. The culture remained sterile on several culture media despite repeated attempts to induce sporulation, and only some chlamydospores were formed. After fermentation in submerged culture and extraction of the cultures with organic solvents, the major secondary metabolites of B. globulariicola were isolated and their chemical structures were elucidated by extensive spectral analysis including nuclear magnetic resonance (NMR) spectroscopy, high-resolution electrospray ionisation mass spectrometry (HRESIMS), and electronic circular dichroism (ECD) measurements. The isolated compounds were tested for their biological activities against various bacteria, fungi, and two mammalian cell lines, but only three of them exhibited weak cytotoxicity against KB3.1 cells, but no antimicrobial effects were observed.

In our ongoing search for new bioactive fungal metabolites, two new cytochalasans were isolated from stromata of the hypoxylaceous ascomycete Hypoxylon fragiforme. Their structures were elucidated via high-resolution mass spectrometry (HR-MS) and nuclear magnetic resonance (NMR) spectroscopy. Together with 23 additional cytochalasans isolated from ascomata and mycelial cultures of different Ascomycota, they were tested on their ability to disrupt the actin cytoskeleton of mammal cells in a preliminary structure–activity relationship study. Out of all structural features, the presence of hydroxyl group at the C7 and C18 residues, as well as their stereochemistry, were determined as important factors affecting the potential to disrupt the actin cytoskeleton. Moreover, reversibility of the actin disrupting effects was tested, revealing no direct correlations between potency and reversibility in the tested compound group. Since the diverse bioactivity of cytochalasans is interesting for various applications in eukaryotes, the exact effect on eukaryotic cells will need to be determined, e.g., by follow-up studies involving medicinal chemistry and by inclusion of additional natural cytochalasans. The results are also discussed in relation to previous studies in the literature, including a recent report on the anti-Biofilm activities of essentially the same panel of compounds against the pathogenic bacterium, Staphylococcus aureus.

Cyst nematodes are globally important pathogens in agriculture. Their sedentary lifestyle and long-term association with the roots of host plants render cyst nematodes especially good targets for attack by parasitic fungi. In this context fungi were specifically isolated from nematode eggs of the cereal cyst nematode Heterodera filipjevi. Here, Ijuhya vitellina (Ascomycota, Hypocreales, Bionectriaceae), encountered in wheat fields in Turkey, is newly described on the basis of phylogenetic analyses, morphological characters and life-style related inferences. The species destructively parasitises eggs inside cysts of H. filipjevi. The parasitism was reproduced in in vitro studies. Infected eggs were found to harbour microsclerotia produced by I. vitellina that resemble long-term survival structures also known from other ascomycetes. Microsclerotia were also formed by this species in pure cultures obtained from both, solitarily isolated infected eggs obtained from fields and artificially infected eggs. Hyphae penetrating the eggshell colonised the interior of eggs and became transformed into multicellular, chlamydospore-like structures that developed into microsclerotia. When isolated on artificial media, microsclerotia germinated to produce multiple emerging hyphae. The specific nature of morphological structures produced by I. vitellina inside nematode eggs is interpreted as a unique mode of interaction allowing long-term survival of the fungus inside nematode cysts that are known to survive periods of drought or other harsh environmental conditions. Generic classification of the new species is based on molecular phylogenetic inferences using five different gene regions. I. vitellina is the only species of the genus known to parasitise nematodes and produce microsclerotia. Metabolomic analyses revealed that within the Ijuhya species studied here, only I. vitellina produces chaetoglobosin A and its derivate 19-O-acetylchaetoglobosin A. Nematicidal and nematode-inhibiting activities of these compounds have been demonstrated suggesting that the production of these compounds may represent an adaptation to nematode parasitism.