Large-Scale Biotechnological Production of the Antileukemic Marine Natural Product Sorbicillactone A

In the search for novel bioactive compounds from sponge-derived microorganisms, we have recently identified two structurally and biosynthetically unprecedented fungal metabolites, the novel-type alkaloids sorbicillactone A and sorbicillactone B. Sorbicillactone A is active against leukemia cells without showing notable cytotoxicity. Therefore, we have developed an efficient process for its biotechnological production and isolation on a large scale supplying sufficient material for the ongoing preclinical investigations and structure-activity relationship (SAR) studies

Carnivory on demand: phosphorus deficiency induces glandular leaves in the African liana Triphyophyllum peltatum

Triphyophyllum peltatum, a rare tropical African liana, is unique in its facultative carnivory. The trigger for carnivory is yet unknown, mainly because the plant is difficult to propagate and cultivate. This study aimed at identifying the conditions that result in the formation of carnivorous leaves. In vitro shoots were subjected to abiotic stressors in general and deficiencies of the major nutrients nitrogen, potassium and phosphorus in particular, to trigger carnivorous leaves' development. Adventitious root formation was improved to allow verification of the trigger in glasshouse-grown plants. Among all the stressors tested, only under phosphorus deficiency, the formation of carnivorous leaves was observed. These glandular leaves fully resembled those found under natural growing conditions including the secretion of sticky liquid by mature capture organs. To generate plants for glasshouse experiments, a pulse of 55.4 μM α-naphthaleneacetic acid was essential to achieve 90% in vitro rooting. This plant material facilitated the confirmation of phosphorus starvation to be essential and sufficient for carnivory induction, also under ex vitro conditions. Having established the cultivation of T. peltatum and the induction of carnivory, future gene expression profiles from phosphorus starvation-induced leaves will provide important insight to the molecular mechanism of carnivory on demand

Rubritalea marina gen. nov., sp. nov., a marine representative of the phylum 'Verrucomicrobia', isolated from a sponge (Porifera)

A marine bacterium, strain Pol012T, was isolated from the Mediterranean sponge Axinella polypoides and subsequently characterized as belonging to subphylum 1 of the phylum ‘Verrucomicrobia’. Strain Pol012T was non-motile, Gram-negative, coccoid or rod-shaped and red in colour. The menaquinones MK-8 and MK-9 were detected. The G+C content of the genomic DNA was 50.9 mol%. Growth was possible at temperatures between 8 and 30 °C and at pH values between 6.8 and 8.2. The closest cultured relative of strain Pol012T was Akkermansia muciniphila (83 % sequence similarity), while the closest environmental 16S rRNA gene sequence was the marine clone Arctic96BD-2 (95 % sequence similarity). Strain Pol012T is the first marine pure-culture representative of ‘Verrucomicrobia’ subphylum 1 and represents a novel genus and species, for which the name Rubritalea marina gen. nov., sp. nov. is proposed. The type strain is Pol012T (=DSM 177716T=CIP 108984T). The GenBank/EMBL/DDBJ accession number for the 16S rRNA gene sequence of strain Pol012T is DQ302104, and those for verrucomicrobial 16S rRNA gene sequences from sponges and seawater are DQ302105–DQ302120

Tajixanthonhydrat und dessen Verwendung zur Behandlung von Tumorerkrankungen

Es werden Tajixanthonhydrat sowie Tajixanthonhydrat-Derivate der allgemeinen Formel I $F1 beschrieben sowie ein Verfahren zu ihrer Herstellung. Tajixanthonhydrat besitzt u. a. eine ausgeprägte Biofilm-inhibierende Wirkung gegen Staphylococcus epidermidis

Antiplasmodial ealapasamines A-C,'mixed' naphthylisoquinoline dimers from the Central African liana Ancistrocladus ealaensis

Three unusual heterodimeric naphthylisoquinoline alkaloids, named ealapasamines A-C (1-3), were isolated from the leaves of the tropical plant Ancistrocladus ealaensis J. Léonard. These 'mixed', constitutionally unsymmetric dimers are the first stereochemically fully assigned cross-coupling products of a 5,8'- and a 7,8'-coupled naphthylisoquinoline linked via C-6' in both naphthalene portions. So far, only two other West and Central Ancistrocladus species were known to produce dimers with a central 6,6″-axis, yet, in contrast to the ealapasamines, usually consisting of two 5,8'-coupled monomers, like e.g., in michellamine B. The new dimers 1-3 contain six elements of chirality, four stereogenic centers and the two outer axes, while the central biaryl axis is configurationally unstable. The elucidation of the complete stereostructures of the ealapasamines was achieved by the interplay of spectroscopic methods including HRESIMS, 1D and 2D NMR (in particular ROESY measurements), in combination with chemical (oxidative degradation) and chiroptical (electronic circular dichroism) investigations. The ealapasamines A-C display high antiplasmodial activities with excellent half-maximum inhibition concentration values in the low nanomolar range

Decandrinin, an unprecedented C9C_9-spiro-fused 7,8-seco−ent seco-ent-abietane from the Godavari mangrove Ceriops decandraCeriops\ decandra

Decandrinin (1), an unprecedented $C_9$-spiro-fused 7,8-$seco-ent$-abietane, was obtained from the bark of an Indian mangrove, $Ceriops\ decandra$, collected in the estuary of Godavari, Andhra Pradesh. The constitution and the relative configuration of 1 were determined by HRMS (ESI) and extensive NMR investigations, and the absolute configuration by circular dichroism (CD) and optical-rotatory dispersion (ORD) spectroscopy in combination with quantum-chemical calculations. Decandrinin is the first 7,8-$seco-ent$-abietane

Nature’s Lab for Derivatization: New and Revised Structures of a Variety of Streptophenazines Produced by a Sponge-Derived Streptomyces Strain

Eight streptophenazines (A–H) have been identified so far as products of Streptomyces strain HB202, which was isolated from the sponge Halichondria panicea from the Baltic Sea. The variation of bioactivities based on small structural changes initiated further studies on new derivatives. Three new streptophenazines (I–K) were identified after fermentation in the present study. In addition, revised molecular structures of streptophenazines C, D, F and H are proposed. Streptophenazines G and K exhibited moderate antibacterial activity against the facultative pathogenic bacterium Staphylococcus epidermidis and against Bacillus subtilis. All tested compounds (streptophenazines G, I–K) also showed moderate activities against PDE 4B

O-Verbrückte Angucyclinone, Verfahren zu ihrer Herstellung, sie enthaltende Arzneimittel und deren Verwendung

Es werden das verbrückte Angucyclinon Gephyromycin (1a) und Derivate dieser Verbindung nach der allgemeinen Formel 1 beschrieben sowie ein Verfahren zu ihrer Herstellung. Diese Substanzen erhöhen die intrazelluläre Calciumkonzentration in Neuronen. Weiterhin besitzen sie eine antibiotische Wirkung gegenüber Gram-positiven Bakterien

Modeling antibiotic and cytotoxic effects of the dimeric isoquinoline IQ-143 on metabolism and its regulation in Staphylococcus aureus, Staphylococcus epidermidis and human cells

Background: Xenobiotics represent an environmental stress and as such are a source for antibiotics, including the isoquinoline (IQ) compound IQ-143. Here, we demonstrate the utility of complementary analysis of both host and pathogen datasets in assessing bacterial adaptation to IQ-143, a synthetic analog of the novel type N,C-coupled naphthyl-isoquinoline alkaloid ancisheynine. Results: Metabolite measurements, gene expression data and functional assays were combined with metabolic modeling to assess the effects of IQ-143 on Staphylococcus aureus, Staphylococcus epidermidis and human cell lines, as a potential paradigm for novel antibiotics. Genome annotation and PCR validation identified novel enzymes in the primary metabolism of staphylococci. Gene expression response analysis and metabolic modeling demonstrated the adaptation of enzymes to IQ-143, including those not affected by significant gene expression changes. At lower concentrations, IQ-143 was bacteriostatic, and at higher concentrations bactericidal, while the analysis suggested that the mode of action was a direct interference in nucleotide and energy metabolism. Experiments in human cell lines supported the conclusions from pathway modeling and found that IQ-143 had low cytotoxicity. Conclusions: The data suggest that IQ-143 is a promising lead compound for antibiotic therapy against staphylococci. The combination of gene expression and metabolite analyses with in silico modeling of metabolite pathways allowed us to study metabolic adaptations in detail and can be used for the evaluation of metabolic effects of other xenobiotics