Investigation of class III and IV lanthipeptide processing enzymes, lanthipeptidetailoring enzymes and of lanthipeptides in epitope grafting

III类和IV类羊毛肽加工酶、羊毛肽剪裁酶以及羊毛肽在表位移植中的研究

• 批准号: 309199717
• 负责人: Dr. Julian Hegemann
• 金额: --
• 依托单位: Helmholtz-Institut für Pharmazeutische Forschung Saarland
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/309199717?language=en
• 关键词: Investigation; class; III; IV; lanthipeptide

Lanthipeptides are an interesting and diverse class of natural products, about which still much is to discover. In context of this research project, different aspects of this research area will be tackled. Initially, the biosynthesis and enzymes of class III and IV lanthipeptides will be investigated, as these classes are so far the least thorough studied ones and hence there are still many question unanswered for these systems. Furthermore, it is planned to isolate novel putative lanthipeptide tailoring enzymes, which are assumed to introduce so far unseen chemical modifications into lanthipeptide structures. The final research aspect is at the same time the most application driven one. Here, it shall be tested if and how good lanthipeptide scaffolds can be utilized for epitope grafting approaches, i.e. the incorporation of small bioactive peptide epitopes into the sequence of a stable peptide scaffold. In summary, the goal of this project is thus to contribute to the research involved in the elucidation of the mechanism behind the biosynthesis of class III and IV lanthipeptides and of possible tailoring enzymes, as well as to probe, if this class of natural products is suitable as scaffold for drug development.

Lanthipeptides是一类有趣且多样的天然产物，关于它还有很多东西要发现。在这个研究项目的背景下，这个研究领域的不同方面将得到解决。最初，将研究III类和IV类羊毛硫肽的生物合成和酶，因为这些类是迄今为止研究最不彻底的，因此这些系统仍然有许多问题没有答案。此外，计划分离新的推定羊毛硫肽剪裁酶，假定其将迄今未见的化学修饰引入羊毛硫肽结构中。最后一个研究方面是同时最受应用驱动的方面。在此，应测试是否以及如何将良好的羊毛硫肽支架用于表位移植方法，即将小的生物活性肽表位掺入稳定的肽支架的序列中。总之，本项目的目标是，因此，有助于研究参与阐明背后的III类和IV类lanthipeptides和可能的剪裁酶的生物合成的机制，以及探测，如果这类天然产物是适合作为药物开发的支架。

项目成果

Investigation of the Biosynthesis of the Lasso Peptide Chaxapeptin Using an E. coli-Based Production System.

• DOI: 10.1021/acs.jnatprod.8b00392
• 发表时间: 2018-09
• 期刊: Journal of natural products
• 影响因子: 5.1
• 作者: Helena Martin-Gómez;U. Linne;F. Albericio;Judit Tulla-Puche;J. Hegemann