Interdisciplinary studies on non-ribosonmally synthesised secondary metabolites from Paenibacillus larvae

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The honey bee is one of the most important lifestock to human. The spore forming bacterium Paenibacillus larvae is the causative agent of the american foulbrood and a worldwide occurring pathogen. Sequencing of the genome of P. larvae facilitated the identification of secondary metabolite gene clusters of four compound classes: the siderophore bacillibactin, the lipopeptide paenilarvin, the tripeptide sevadicin and the peptide/polyketide-hybrid compound paenilamicin. The research to be performed within the project is dedicated to the investigation of 1) the prodrug-activation of prepaenilamicin, 2) the mechanism of resistance of the paenilamicin producer and 3) the thioesterase (TE)-independant termination mechanism of the biosynthesis. Furthermore we aim at a deepened understanding of the function of secondary metabolites in the pathogenesis of P. larvae on the laervae of the honeybee. A further part of the project comprises the total synthesis of paenilamycins and the synthesis of derivatives in order to aid in the determination of the molecular target and the mode of action excerting antibacterial and antifungal bioactivity.