Biosynthese von Legioliulin und anderen Sekundärmetaboliten aus Legionella
Final Report Abstract
During the funding periods the following major results were obtained: 1. The biosynthesis of legioliulin was published in ChemBioChem together with the characterization of the phenylalanine ammonium lyase responsible for the biosynthesis of the starter unit cinnamoyl-CoA. 2. The genomes of several Legionella strains have been analysed for biosynthesis gene clusters involved in the production of natural products and several natural products have been predicted. 3. A single Sfp-type PPTase has been identified in all Legionella strains that is involved in fatty acid and natural product biosynthesis. 4. The PPTase can be inhibited by synthetic compounds thus acting as efficient antibiotics against Legionella. Unfortunately, the molecular biology work with Legionella was much more difficult than expected and therefore most of the planned goals were not achieved. Except for the phenylalanine ammonium lyase and the PPTase it was not possible to obtain functional proteins from Legionella in E. coli, although we were able to clone several gene clusters. The reason for this is currently unknown but E. coli might not be the best host strain for Legionella genes. Nevertheless, the finding that Legionella has only one PPTase that can be inhibited might open a possible treatment for Legionella associated diseases. We will perform the purification and in vitro characterization of the PPTase and its substrate carrier proteins during future Master theses and then resubmit this aspect of the work.
Publications
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Biosynthesis of the natural fluorophore legioliulin from Legionella, ChemBioChem, 2013, 14, 1415-1418
T. Ahrendt, M. Miltenberger, I. Haneburger, F. Kirchner, M. Kronenwerth, A. O. Brachmann, H. Hilbi, H. B. Bode
