Kathrin Wittstein

Helmholtz Centre for Infection Research | HZI · Department Microbial Drugs (MWIS)

Current treatment of Chlamydia trachomatis using doxycycline and azithromycin introduces detrimental side effects on the host's microbiota. As a potential alternative treatment, the myxobacterial natural product sorangicin A (SorA) blocks the bacterial RNA polymerase. In this study we analyzed the effectiveness of SorA against C. trachomatis in cel...

Neurotrophins such as nerve growth factor (ngf) and brain-derived neurotrophic factor (bdnf) play important roles in the central nervous system. They are potential therapeutic drugs for the treatment of neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. In this study, we investigated the neurotrophic properties of tr...

Neurotrophins such as nerve growth factor (ngf) and brain derived neurotrophic factor (bdnf) play important roles in the central nervous system. They are potential therapeutic drugs for treatment of neurodegerative diseases including Alzheimer's disease and Parkinson's disease. In this study, we investigated the neurotrophic properties of triterpen...

In our continued search for biologically active metabolites from cultures of rare Basidiomycota species, we found eight previously undescribed cyathane-xylosides from submerged cultures of Dentipellis fragilis, which were named dentifragilins A–H. In addition, the known cyathane deriv-atives striatal D and laxitextine A were isolated. All compounds...

The xylariaceous genus Dematophora has recently been resurrected and segregated from Rosellinia based on a molecular phylogeny and morphological characters. This was an important taxonomic change because Dematophora in the current sense contains several important pathogens, while Rosellinia is limited to mainly saprotrophic species that have an end...

Medicinal mushrooms of the genus Hericium are known to produce secondary metabolites with homeostatic properties for the central nervous system. We and others have recently demonstrated that among these metabolites cyathane diterpenoids and in particular erinacine C possess potent neurotrophin inducing properties in astrocytic cells. Yet, the signa...

Background: Hepatocellular carcinoma (HCC) represents a major health burden with limited curative treatment options. There is a substantial unmet need to develop innovative approaches to impact the progression of advanced HCC. Haprolid is a novel natural component isolated from myxobacteria. Haprolid has been reported as a potent selective cytotoxi...

Rosellinia (Xylariaceae) is a large, cosmopolitan genus comprising over 130 species that have been defined based mainly on the morphology of their sexual morphs. The genus comprises both lignicolous and saprotrophic species that are frequently isolated as endophytes from healthy host plants, and important plant pathogens. In order to evaluate the u...

Rosellinia (Xylariaceae) is a large, cosmopolitan genus comprising over 130 species that have been defined based mainly on the morphology of their sexual morphs. The genus comprises both lignicolous and saprotrophic species that are frequently isolated as endophytes from healthy host plants, and important plant pathogens. In order to evaluate the u...

Fermentation of the fungal strain Skeletocutis sp. originating from Mount Elgon Natural Reserve in Kenya, followed by bioassay guided fractionation led to the isolation of twelve previously undescribed metabolites named skeletocutins A-L (1-5, 7-13) together with the known tyromycin A (6). Their structures were assigned by NMR spectroscopy compleme...

Chemical analysis of extracts from cultures of the plant pathogenic fungus Cytospora sp. strain CCTU A309 collected in Iran led to the isolation of two previously unreported heptanedioic acid derivatives namely (2R,3S) 2-hydroxy-3-phenyl-4-oxoheptanedioic acid (1) and (2S,3S) 2-hydroxy-3-phenyl-4-oxoheptanedioic acid (2) as diastereomers, four prev...

During the course of our ongoing work to discover new inhibitors of biofilm formation of Staphylococcus aureus from fungal sources, we observed biofilm inhibition by cytochalasans isolated from cultures of the ascomycete Hypoxylon fragiforme for the first time. Two new compounds were purified by a bioassay-guided fractionation procedure; their stru...

Complexity‐generating chemical transformations that afford novel molecular scaffolds enriched in sp³ character are highly desired. Here, we present a highly stereoselective scaffold diversity synthesis approach that utilizes cascade double‐annulation reactions of diverse pairs of zwitterionic and non‐zwitterionic partners with 3‐formylchromones to...

Background: Within the polymicrobial dental plaque biofilm, bacteria kill competitors by excreting mixtures of bacteriocins, resulting in improved fitness and survival. Inhibiting their bacteriocin synthesis might therefore be a useful strategy to eliminate specific pathogens. We used Streptococcus mutans, a highly acidogenic inhabitant of dental...

Basidiomycetes of the genus Hericium are among the most praised medicinal and edible mushrooms, which are known to produce secondary metabolites with the potential to treat neurodegenerative diseases. This activity has been attributed to the discovery of various terpenoids that can stimulate the production of nerve growth factor (NGF) or (as establ...

Amanita ballerina and A. brunneitoxicaria spp. nov. are introduced from Thailand. Amanita fuligineoides is also reported for the first time from Thailand, increasing the known distribution of this taxon. Together, those findings support our view that many taxa are yet to be discovered in the region. While both morphological characters and a multipl...

Phylogenetic tree inferred by Maximum Likelihood analysis of β-tubulin sequences. Bootstrap values (BS) ≥70% are shown above the branches. Amanita species with sequences generated in this study are highlighted in bold. Voucher collection identifiers are provided after each species name. (EMF)

Phylogenetic tree inferred by Maximum Likelihood analysis of rpb2 sequences. Bootstrap values (BS) ≥70% are shown above the branches. Amanita species with sequences generated in this study are highlighted in bold. Voucher collection identifiers are provided after each species name. (EMF)

Phylogenetic tree inferred by Maximum Likelihood analysis of ITS1+5.8S+ITS2 sequences. Bootstrap values (BS) ≥70% are shown above the branches. Amanita species with sequences generated in this study are highlighted in bold. Voucher collection identifiers are provided after each species name. (EMF)

Agaricus subrufescens (almond mushroom) was first collected in America, but has been cultivated worldwide due to its medicinal properties. The potential health promoting benefits of A. subrufescens have been emphasized in several reports and include tumor growth reduction, antimicrobial, immunostimulatory and anti-allergy effects. A unique class of...

Lepista sordida is an edible and medicinal mushroom, but until now it had to be collected from the wild. The present study is the first report of the successful cultivation of a wild strain of L. sordida from Thailand. The morphological description and molecular examination of the fungus are included, in order to confirm the identification of the s...

Three new natural products, corallocins A-C (1-3), along with two known compounds were isolated from the mushroom Hericium coralloides. Their benzofuranone and isoindolinone structures were elucidated by spectral methods. All corallocins induced nerve growth factor and/or brain-derived neurotrophic factor expression in human 1321N1 astrocytes. Furt...

Histone posttranslational modifications (HPTMs) are involved in chromatin-based regulation of fungal secondary metabolite biosynthesis (SMB) in which the corresponding genes-usually physically linked in co-regulated clusters-are silenced under optimal physiological conditions (nutrient-rich) but are activated when nutrients are limiting. The exact...

Acetylation levels of the genes de-regulated in the kdmBΔ mutant largely mirror transcriptional activities. The genes deregulated in the kdmB mutant and previously subdivided into four differentially methylated H3K4me3 groups (group 1 to group 4 genes, Fig 5) were subjected here to analysis of acetylation levels. Identical to the bioinformatic proc...

KdmB does not influence chromosomal distribution of H3K36me3. (A) H3K36me3 pattern of genes in primary metabolism. The graph shows a comparison of H3K36me3 levels between WT and kdmBΔ. Because H3K36 methylation is located predominantly at the last third of reading frames, the predicted STOP codons of all genes were aligned and set as starting point...

Distribution of the analysed histone marks [log2CPM] and RNA-seq reads (log2 RPKM) in and around the sterigmatocystin (ST) gene cluster during primary (17 h) and secondary (48 h) metabolism in the WT. Structural genes belonging to the biosynthetic gene cluster are indicated by the red boxed area. The genes belonging to the cluster have been previou...

Distribution of the analysed histone marks [log2CPM] and RNA-seq reads (log2 RPKM) in and around the austinol (AUS) gene cluster during primary (17 h) and secondary (48 h) metabolism in the WT. Structural genes belonging to the two split biosynthetic gene cluster responsible for the biosynthesis of austinol are indicated by the two red boxed areas....

Distribution of selected histone marks [log2CPM] and RNA-seq reads (log2 RPKM) of the neighboring orsellinic acid (ORS) gene cluster [103] and DBA gene cluster [108]. Distribution of the analysed histone marks [log2CPM] and RNA-seq reads (log2 RPKM) in and around the clusters are shown for wild type cells in primary (17 h) and secondary (48 h) meta...

Distribution of selected histone marks [log2CPM] and RNA-seq reads (log2 RPKM) of the monodictiphenon (MDP), gene Distribution of selected histone marks [log2CPM] and RNA-seq reads (log2 RPKM) of the asperthecin (APT) gene cluster. Distribution of the analysed histone marks [log2CPM] and RNA-seq reads (log2 RPKM) in and around the cluster are shown...

List of strains used in this study. (DOCX)

KdmB has demethylase activity but low specificity in vitro. A. Schematic representation of the KdmB-GST fusion heterologously expressed in E. coli. The Coomassie stained SDS-PAGE Gel shows the purified GST-KdmB fusion protein and the arrow indicates protein migration at the expected size of around 130 kDa. 1–3 μg of purified GST-KdmB were loaded on...

LC- MS/MS Base Peak Chromatograms (BPC). Ratios of differently modified variants of the histone H3 K9STGGK14APR and H3 K27AAPSTGGVK36K37PHR peptide from WT and kdmBΔ. (TIF)

List of oligonucleotides used in this study. (DOCX)

kdmB deletion does not alter the growth rate. (A) Measurement of glucose and nitrate concentration in Aspergillus Minimal Medium (AMM) supernatants from WT and kdmBΔ 22h cultures. (B) Equal amount of WT and kdmBΔ spores were point inoculated on solid AMM. Picture was taken after 48h. (TIF)

Genome viewer image of the chromatin landscape and transcription profile of the penicillin gene cluster during primary (PM) and secondary metabolism (SM) in WT cells. The penicillin (PEN) cluster (red box, as defined in [105]) is located between heterochromatic domains at the subtelomeric region of chromosome VI. The cluster is known to be partiall...

Distribution of selected histone marks [log2CPM] and RNA-seq reads (log2 RPKM) of the terrequinone (TDI) gene cluster. Distribution of the analysed histone marks [log2CPM] and RNA-seq reads (log2 RPKM) in and around the cluster are shown for wild type cells in primary (17 h) and secondary (48 h) metabolism phase. Structural genes belonging to the b...

Distribution of selected histone marks [log2CPM] and RNA-seq reads (log2 RPKM) of the asperthecin (APT) gene cluster. Distribution of the analysed histone marks [log2CPM] and RNA-seq reads (log2 RPKM) in and around the cluster are shown for wild type cells in primary (17 h) and secondary (48 h) metabolism phase. Structural genes belonging to the bi...

LC-MS and LC-MS2 data of detected metabolites (a) HR-ESI-MS; b) LC/ESI-MS; c) LC/ESI+-MS2. (TIF)

Comparison between wild type and kdmBΔ cells for their association between H3K4me3 levels and gene transcription in 48 h SM cultures. Metaplots for H3K4me3 levels in genes belonging to the group with low average H3K4me3 levels in the wild type (log2 RPKM ≤ 5; group 5 and group 6 genes) and high average H3K4me3 levels in the wild type (log2 RPKM > 5...

Bioassay-guided fractionation of the mycelial extract of a basidiomycete culture collected in Kenya led to the isolation of two new cyathane diterpenoids named laxitextines A (1) and B (2). The producer strain was characterized by detailed taxonomic studies based on rDNA using the 5.8S gene region, the internal transcribed spacer 2 (ITS2), and part...

DOI 10.1007/s11557-015-1105-4. Online Medicinal mushrooms have become a compelling topic because the bioactive compounds they contain promise a plethora of therapeutic properties. Hericium erinaceus commonly known as “Houtou” or “Shishigashira” in China and “Yamabushitake” in Japan, has commonly been prescribed in Traditional Chinese Medicine (TCM)...

The taxonomic and nomenclatural history of the genus Ganoderma and related basidiomycetes is reviewed and compared to recent studies on its molecular phylogeny. A basidiomycete belonging to the genus Ganoderma can often rather easily be recognised in the field from the macro-morphological characters of the sporocarp. The most important species and...

A cascade double-annulation strategy employing diverse pairs of zwitterions with 3-formylchromones is presented that provides stereoselective access to complex tetracyclic benzopyrones. Different zwitterions incorporated different rings that include aza-, oxa-, and carbocycles fused to a common benzopyrone scaffold and in the process created three...

The desired products are obtained as separable E/Z-mixtures.

N-Phenyl-C-chromonyl nitrones 1 and the allenoate zwitterion 2, generated by addition of phosphine to acetylenedicarboxylates, undergo a cascade reaction sequence involving an unprecedented [5+3] annulation followed by deoxygenative rearrangement leading to dihydropyridine-fused benzopyrones. Unusual electronic control by the N-substituents of 1 di...

A silver catalyzed and microwave assisted one-pot cascade synthesis provides efficient access to diverse alkaloid-inspired scaffold classes, and a concise and efficient total synthesis of homofascaplysin C and fascaplysin.