Land-use and land-cover change (LUCC), which is a general term for the human modification of the Earth’s terrestrial surface, increasingly gains attention in the scientific community, due to its vast global extent and the ...

Aberrant epigenetic changes in DNA methylation and histone acetylation are hallmarks of most cancers, while histone methylation had been considered to be irreversible and less versatile. Recently, several histone demethylases ...

Der chronische Verlauf der Entzündungserkrankungen erfordert einen langfristigen Einsatz, wodurch die Wahrscheinlichkeit des Auftretens schwerwiegender, systemischer Nebenwirkungen bei der Anwendung der meisten Pharmaka ...

The perennial presence of ice in permafrost rock walls alters thermal, hydraulic and mechanic properties of the rock mass. Temperature-related changes in both, rock mechanical properties (compressive and tensile strength ...

The first section of this work comprises investigations concerning the initial steps in rifamycin biosynthesis. The amino sugar kanosamine was described to represent the most likely source of the nitrogen atom in the aminoshikimate pathway and is putatively synthesised by the catalytic activity of the enzymes RifL, RifK and RifM. Furthermore, in earlier studies kanosamine was even converted to kanosamine 6-phosphate by the rifamycin biosynthetic enzyme RifN. Therefore, evidence but no proof for the occurrence of kanosamine at an early stage in rifamycin biosynthesis was provided before the beginning of the present work. In this work functional studies of the gene products of rifL, rifK and rifM from the rifamycin producer Amycolatopsis mediterranei S699 were carried out using the plasmid pHGF7604 for the heterologous expression of the rifG-N genes in Streptomyces lividans TK24. Kanosamine was supposed to be synthesised by RifL, RifK and RifM during the RifL assay, employing a cell-free extract of Streptomyces lividans pHGF7604. These studies were based on former results concerning the RifL assay and aimed at the analytical detection of the putatively synthesised intermediate kanosamine en route to the known ansamycin precursor AHBA. Therefore, the RifL assay system was optimised, protein purification of cell-free extracts from Streptomyces lividans pHGF7604 was performed and analytical methods for kanosamine detection were developed within the scope of this study. The amino sugar was not detected in any RifL incubation sample, whereas concurrently no RT-PCR product of RifL could be verified. However, actual proof for an involvement of rifL, rifK and rifM in the postulated biosynthetic pathway of rifamycin could not be demonstrated under the terms of this study.<br /> The second section of this work is directed towards the characterisation of the gene cluster encoding the biosynthesis of the polycyclic xanthone IB-00208 in Streptomyces sp. GW2/5831. As polyketides represent an important source of nature-derived pharmaceuticals, their exploration provides promising opportunities for the discovery of new biogenic agents. Moreover, the acquirement of insights on the genetic level provides important information for genetic engineering that can lead to novel hybrid compounds with improved therapeutic values. In polyketide gene clusters “core” polyketide synthase (PKS) genes are encountered along with “post” PKS genes encoding modifying enzymes like oxygenases, methyl- and glycosyltransferases. In particular, glycosylation reactions that take place during post-PKS tailoring processes are relevant for genetic engineering. Especially genes encoding glycosyltransferases that catalyse (deoxy-) sugar attachments to the matured molecule are focussed on. The information obtained in this part of the work should provide a prerequisite for a prospective genetic engineering of the IB-00208 and griseorhodin A biosynthetic pathways. A glycosylated griseorhodin A molecule is expected to feature improved pharmacokinetic properties. As both compounds share the same polyaromatic core skeleton, it can be envisioned that griseorhodin A will be accepted as an aglycon-substrate by the glycosylating enzyme from the IB-00208 cluster. To isolate the IB-00208 cluster, a genomic library was established from DNA of Streptomyces sp. GW2/5831, and screening was performed employing ketosynthase (KS) primers. Sequencing of the positive cosmid clones and subsequent BLAST search allowed the deduction of a putative cluster fragment containing protein coding regions characteristic of this kind of PKS clusters, and genes possibly involved in the biosynthesis of IB-00208 were identified. The library was constructed using a shuttle vector that enabled the heterologous expression of the cosmid sequences in Streptomyces albus. This study sets the stage for further investigations of the IB- 00208 biosynthetic gene cluster from Streptomyces sp. GW2/5831.<br /> Both parts of the study are in the field of actinomycete genetics in drug development, representing different types of PKS systems. The genetics of streptomycetes is of particular importance, as it opens up many possibilities in the fields of biotechnology and pharmacy. Therefore many sequencing projects contribute to an enlarged knowledge on biosynthetic gene clusters of therapeutic agents that are of substantial interest....

Immune mediated glomerulonephritis (GN) is a major cause renal inflammation leading to terminal kidney failure. B cells and autoantibodies are well known to contribute to the progression of glomerular disease. The role of ...

<p>Packungsbeilagen sollen das Informationsbedürfnis des Patienten zum Arzneimittel und zu dessen sicherer Anwendung erfüllen. Außerdem sollen sie die Patienten-Compliance steigern. Derzeitige Packungsbeilagen führen ...

Cosmology has recently entered an era of increasingly rich observational data sets, all being in agreement with a cosmological standard model that features only a small number of free parameters. One of the most powerful ...

The present work investigates the state-selective transport of single neutral cesium atoms in a one-dimensional optical lattice. It demonstrates experimental applications of this transport, including a single atom ...

Extensive sheep and goat grazing provides the main income for population in Morocco’s semi-arid to arid areas where rainfall does not permit cropping without irrigation. As processes of vegetation dynamics cannot be assessed ...