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Non-ribosomal peptide synthesis

非核糖体肽合成

基本信息

批准号：
152010838
负责人：
Professor Dr. Mohamed A. Marahiel
金额：
--
依托单位：
Fachgebiet Biochemie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2009
资助国家：
德国
起止时间：
2008-12-31 至 2013-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/152010838?language=en
关键词：
Non ribosomal peptide synthesis

项目摘要

This project is dedicated towards the understanding of the biochemical and structural aspects of tailoring enzymes involved in non-ribosomal peptide synthesis and non-ribosomal peptide synthetases (NRPS), including those who go beyond the classical co-linearity rules. We would like to investigate substrate modifying enzymes associated with Cß-carbon functionalization and piperazic acid synthesis during kutznerides assembly. Furthermore, we will screen bacterial strains containing sequences encoding for interesting NRPSs or modifying enzymes with our well established radio-HPLC-MS detection method (global genome mining approach) to identify novel NRPs produced by Clostridium thermocellum, Herpetosiphon aurantiacus and Saccharopolyspora erythraea. We will start with the biochemical characterization of the biosynthetic assembly line for a cyclic glycosylated sugardipeptide that represents an archetype of a new NRPS product class from C. thermocellum and H. aurantiacus and analyze in parallel a biosynthesis pathway from 5. erythraea for an unusual tryptophan halogenation. In the third part of this proposal we would like to perform intense structural studies on several NRPS modules by employing a new chemical PCPtrapping method utilizing non-hydrolysable amino-Coenzyme A derivatives as well as covalent linkages between catalytic subunits to restrict the domain motion during crystallization.

该项目致力于了解参与非核糖体肽合成和非核糖体肽合成酶（NRPS）的剪裁酶的生物化学和结构方面，包括那些超越经典共线性规则的酶。我们希望研究在库茨内酯组装过程中与碳-碳官能化和哌嗪酸合成相关的底物修饰酶。此外，我们将筛选含有编码感兴趣的NRPS或修饰酶的序列的细菌菌株，采用我们完善的放射性HPLC-MS检测方法（全球基因组挖掘方法），以鉴定由热纤梭菌、橙色疱疹病毒和多孢菌产生的新型NRPs。我们将从生物合成装配线的生物化学表征环糖基化糖二肽，代表了一个新的NRPS产品类的原型，从C。热纤维素和H.并平行分析来自5. erythraea用于不寻常的色氨酸卤化。在本提案的第三部分中，我们希望通过采用一种新的化学PCP捕获方法，利用不可水解的氨基辅酶A衍生物以及催化亚基之间的共价键来限制结晶过程中的结构域运动，对几个NRPS模块进行深入的结构研究。