Novel ribosomally synthesized peptide antibiotics from microbial genomes

羊毛硫抗生素（含羊毛硫抗生素）和噻唑/恶唑抗生素是基因编码的，核糖体合成的肽，通常显示抗菌活性。两组的前肽显示出相似性。产生羊毛硫氨酸、噻唑/恶唑环或其他修饰的氨基酸的修饰是由在生物合成基因簇中的结构基因附近编码的独特酶引入的。该项目的重点将是lantibiotics和噻唑/恶唑抗生素的表达，这些抗生素在测序的细菌基因组中编码，但尚未被表征。三种新测序菌株的推定硫醚抗生素，包括地衣芽孢杆菌B基因组中的一个成员和几个宏基因组序列以及不寻常的噻唑/恶唑化合物。cereus和P. cereingae进行研究。对于肽的表达，将采用大部分异源表达和体外修饰系统。这些实验将包括对所产生的化合物进行初步表征，并评估其作为新抗菌剂的潜力。有希望的物质将根据其作用方式进行表征。

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.