GenoMik-Transfer - Anwendungsorientierte Genomforschung an Mikroorganismen

Verbundprojekt: ChemBiofilm / Beschreibung Teilprojekt

Teilprojekt 6: Chemische Analyse von Biofilminhibitions-Strategien und chemische Synthese

Laufzeit: 01.02.10-31.10.13

Projektleiter:

Prof. Dr. Stephanie Grond, Eberhard-Karls-UniversitÃ¤t TÃ¼bingen

The aim of the project 'new anti-biofilm strategies from the metagenomes' as part of the GenoMik-Transfer-program (financed by Federal Ministry of Education and Research) is the identification of new biofilm inhibitors to prevent the formation of biofilms. In order to use the potential capacity of so-far non-cultivated organisms, metagenome strategies are utilized. The investigations of bioactive anti-quorum-sensing samples are performed by the interdisciplinary joint project with methods of molecular biology, biochemistry, medicine and organic chemistry.

As the chemistry partner in the research network we aim to establish:

Effective chemical analyses for detection and quantification of compounds, new or known. Especially HPLC-MS-ESI methods are established using the respective substances (e.g. from total synthesis) as internal standards. Hit candidates of metagenomic clones or rather their extracts are investigated in order to conceive the chemical nature of their quorum-quenching-activity.
Isolation and purification procedures for the production of compounds and their structural elucidation.
Chemical total syntheses of potential biofilm inhibitor molecules.

In close cooperation with partners of the biological research groups we exchange extracts of metagenome cultures for chemical analysis, chemical purification and subsequent biological profiling. A set of compounds, microbial secondary metabolites from our cultivations, will be tested for biofilm inhibition and immobilization. A compound library, containing substances which might act as biofilm inhibitors, will be established for biofilm screening purposes. We produce the potential inhibitors by isolation from actinomycetes strains or by chemical synthesis.

Referenzen:

C. Schipper, C. Hornung, P. Bijtenhoorn, M. Quitschau, S. Grond, W. R. Streit (2009). Metagenome-derived clones encoding for two novel lactonase family proteins involved in biofilm inhibition in P. aeruginosa. Appl. Environ. Microbiol. 75, 224-233.

M. Quitschau (2009). Neue Biofilminhibitoren mittels Metagenom-Strategie und marine Streptomyceten, neue Naturstoffe, Synthesen und Biosynthesen. Dissertation, Georg August UniversitÃ¤t GÃ¶ttingen, Institut fÃ¼r organische Chemie.

F. Surup, H. Shojaei, P. von Zezschwitz, B. Kunze, S. Grond (2008). New Iromycins from Streptomyces sp. and Synthesis as Mitochondrial Complex I Inhibitors. Bioorg. Med. Chem., 16, 1738-1746.

F. Surup, O. Wagner, J. von Frieling, M. Schleicher, S. Oess, P. MÃ¼ller, S. Grond (2007). The Iromycins, a New Family of Pyridone Metabolites from Streptomyces sp.: Structure, NOS, Inhibitory Activity and Biosynthesis. J. Org. Chem., 72, 5085-5090.