biosynthesis of the Avionins, a new class of lantibiotics

Avionins（一类新型羊毛硫抗生素）的生物合成

• 批准号: 385052459
• 负责人: Professor Dr. Roderich D. Süßmuth
• 金额: --
• 依托单位: Arbeitsgruppe Biologische Chemie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2017
• 资助国家: 德国
• 起止时间: 2016-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/385052459?language=en
• 关键词: biosynthesis; Avionins; new; class; lantibiotics

The ribosomally synthesised and posttranslationally modified peptide (RiPP) microvionine, isolated from a bacterium related to Actinomycetes, shows interesting antibacterial properties. In addition, it has a new combination of structural motifs, an avionine (avionylcysteine-labionine)-bridge and an N-terminal, bismethylated guanidino fatty acid. Due to its promising properties a deeper investigation of its biosynthesis of this forst lipolanthine (lipidated lanthipeptide) is planned. This should be achieved by modification and mutagenesis of the producing organism as well as by in vitro by protein-biochemical assays. Hence, not only the biosynthesis and the requirements for substrates are investigated, but also on an intermediate time scale derivatives of the drug with altered bioactivity are targeted to be produced. Furthermore, by genome mining more lipolanthine-producers will be identified and the corresponding compounds detected. Hence, a new group of lipidated RiPPs will be studies in-depth and the development of new antimicrobial drugs may be pushed forward.

从与放线菌相关的细菌中分离出的核糖体合成和翻译后修饰肽 (RiPP) microvionine 显示出有趣的抗菌特性。此外，它还具有新的结构基序组合、鸟氨酸（鸟酰半胱氨酸-labionine）桥和 N 末端双甲基化胍基脂肪酸。由于其具有前景的特性，计划对这种原脂兰硫肽（脂化兰硫肽）的生物合成进行更深入的研究。这应该通过生产生物体的修饰和诱变以及通过体外蛋白质生化测定来实现。因此，不仅研究了生物合成和对底物的需求，而且还以中间时间尺度为目标生产具有改变的生物活性的药物衍生物。此外，通过基因组挖掘，将鉴定出更多的硫黄素生产者并检测到相应的化合物。因此，一组新的脂质化RiPP将得到深入研究，并可能推动新型抗菌药物的开发。

项目成果

The anti-staphylococcal lipolanthines are ribosomally synthesized lipopeptides

• DOI: 10.1038/s41589-018-0068-6
• 发表时间: 2018-07-01
• 期刊: NATURE CHEMICAL BIOLOGY
• 影响因子: 14.8
• 作者: Wiebach, Vincent;Mainz, Andi;Suessmuth, Roderich D.
• 通讯作者: Suessmuth, Roderich D.