Novel ribosomally synthesized peptide antibiotics from microbial genomes

Lantibiotics（含硫氨酸类抗生素）和噻唑类/恶唑类抗生素是基因编码、核糖体合成的肽类抗生素，通常具有抗菌活性。两组的前肽具有相似性。产生衣硫氨酸、噻唑/恶唑环或其他修饰氨基酸的修饰是由编码在生物合成基因簇结构基因附近的独特酶引入的。该项目的重点将是抗生素和噻唑/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。本文将对三种新测序菌株的推定抗生素进行研究，包括古细菌的一个成员和几个宏基因组序列，以及来自地衣芽孢杆菌、蜡样芽孢杆菌和丁香芽孢杆菌基因组的不寻常的噻唑/恶唑化合物。对于肽的表达，将主要采用异种表达和体外修饰系统。实验将包括对所产生的化合物进行初步表征，并评估其作为新型抗菌剂的潜力。有前途的物质将根据其作用方式加以描述。

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.