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Bielefeld University > Department of Chemistry > Organic Chemistry III > DAAD
  

DAAD- Research Training Network

Scientific Background

Microbial organisms often produce biologically active and chemically intriguing secondary metabolites. Microbial diversity constitutes an infinite pool of novel chemistry, making up a valuable source for innovative biotechnology. Despite a remarkable improvement of our knowledge in cancer biology and the successful approval of several novel targeted therapies, long term disease control or cure remain the exception rather than the rule in oncology. In many cases tumours develop resistance to therapeutic agents. In addition, most advanced solid tumours remain essentially incurable. This need for better medication renders anticancer drugs a highly attractive field of research. Thus, for facing the demand of high drug efficacy and safety the development of cytotoxic drugs has revived interest in pharmaceutical research. New drugs need to be more specific with low side effects and less toxicity than the ones currently in use. Natural products from plants, endophytic fungi, and microorganisms, especially from extreme habitats are considered promising lead compounds in tumour therapy.

An intensive research effort on extremophiles has been driven during the last decades due the potential biotechnological applications associated with these microbes and their products. The likely potential has been increasing exponentially with the isolation of new microbial strains, the identification of novel compounds and pathways, and the molecular and biochemical characterization of cellular components. These organisms have evolved several structural and chemical adaptations, which allow them to survive and grow in extreme environments. Extreme environments include high temperature, pH, pressure, salt concentration, and low temperature, pH, nutrient concentration and water availability, and also conditions having high levels of radiation, harmful heavy metals and toxic compounds.

Extremophiles from extreme environments like desert sand, the "Sebkha" and "Chott" saline systems in the south of Tunisia received great attention due to special mechanism of adapting to the extreme conditions in their environments and also due to the production of various natural compounds. Novel isolates from desert sand have been recently described that are capable of resisting very stressful conditions including high doses of UV, γ-rays and desiccation, suggesting that these bacteria are well adapted to stressing conditions and that interesting biotechnological properties can be exploited from these organisms.

In our search for novel natural products that can be developed as a resource for biotechnology we have focused on the discovery of novel organisms and argued that the latter may be found particularly, although not exclusively, in unusual and underexplored environments. In this context the saline environment systems (Sebkha, Chott) are proven to be a major source of new natural products, including antimicrobial and anticancer compounds, most notably being expressed by actinomycete bacteria.

The actinomycetes exist in various habitats and represent a ubiquitous group of microbes widely distributed in natural ecosystems around the world. They are primarily soil inhabitants and responsible for the characteristically "earthy" smell of freshly turned healthy soil but have been found widely and distributed in a diverse range of aquatic ecosystem, including sediments obtained from deep sea. Their presence in extreme environments especially at cryophilic region and even from desert soil has been reported.

Actinomycetes are valuable bacteria well exploited in biotechnology for their secondary metabolites. Among various genera of Actinomycetes; Streptomyces, Saccharopolyspora, Amycolatopsis, Micromonospora and Actinoplanes are the major producers of commercially important biomolecules. Actinomycetes, especially Streptomyces species are widely recognized as industrially important microorganisms as they are a rich source of several useful bioactive natural products with potential applications and are prolific producers of secondary metabolites, many of which have commercial importance as antibiotics, anti-parasitics and antifungal agents, herbicides, pesticides, anticancer or immunosuppressive agents as well as industrially important enzymes.

Actinomycetes are of tremendous economic importance as the secondary metabolites produced by them include antibiotics, other therapeutically useful compounds, toxins, pesticides and animal and plant growth factors. The secondary metabolites produced by actinomycetes serve as the sources of life saving environments. These have a broad spectrum of biological activities; e.g. antibacterial (clavulanic acid, streptomycin, tetracycline, chloramphenicol), antifungal (nystatin), antiviral (tunicamycin), antiparasitic (avermectin), immunosuppressive (rapamycin), antitumour (actinomycin, mitomycin C, anthracyclines), and diabetogenic (bafilomycin, streptozotocin), anticancer (doxorubicins, daunorubicin, mitomycin, and bleomycin), and immunosuppressive (cyclosporine and rapamycin) activities. Members of the Actinomycetes group, in addition are producers of clinically useful antitumor drugs such as anthracyclines (aclarubicin, daunomycin and doxorubicin), peptides (bleomycin and actinomycin D), aurelic acids (mithramycin), enediynes (neocarzinstatin), antimetabolites (pentostatin), carzinophilin, mitomycins, etc.

Actinomycetes metabolites are not only known for their potent therapeutic activities but also for the fact that they frequently possess the desirable pharmacokinetic properties required for clinical development, and they are served in pharmaceutical industries and agriculture fields. Actinomycetes also have the potential to inhibit the growth of several plant pathogens e.g. Erwinia amylovora (bacteria that cause fireblight to apple), Agrobacterium tumefaciens (casual agent of Crown Gall disease) etc. Almost 80% of the world´s antibiotics are known to come from actinomycetes, and specially from the genera Streptomyces and Micromonospora.

Among actinomycetes, ~7600 compounds are produced by Streptomyces species. The antibiotics from actinomycete sort into several major structural classes such as amino glycosides, ansamycins, anthracyclines, β-lactams, macrolides and tetracyclines. Actinomycetes are the main source of clinically important antibiotics, most of which are too complex to be synthesized chemically.