Novel ribosomally synthesized peptide antibiotics from microbial genomes

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Lantibiotics (lanthionine containing antibiotics) and thiazole/oxazole antibiotics are gene encoded, ribosomally synthesized peptides which usually display antibacterial activity. The prepeptides of both groups show similarities. The modifications that yield lanthionine, thiazole/oxazole rings or other modified amino acids are introduced by unique enzymes which are encoded in the vicinity of the structural genes in biosynthetic gene clusters. The focus of the project will be the expression of lantibiotics and thiazole/oxazole antibiotics that are encoded in sequenced bacterial genomes but have not yet been characterized. The putative lantibiotics of three newly sequenced strains, including a member of the Archaea and several metagenomic sequences as well as unusual thiazole/oxazole compounds from the genomes of Bacillus licheniformis, B. cereus and P. syringae will be investigated. For expression of the peptides, mostly heterologous expression and in vitro modification systems will be employed. The experiments will comprise a preliminary characterization of the compounds produced and an evaluation of their potential as new antimicrobials. Promising substances will be characterized as to their mode of action.