Biosynthetic and toxic potential of ergot: Biological activity of ergot alkaloids and genome mining for the identification further potential toxic secondary metabolites

麦角的生物合成和毒性潜力：麦角生物碱的生物活性和基因组挖掘，用于鉴定进一步潜在的有毒次生代谢物

• 批准号: 227350539
• 负责人: Professor Dr. Hans-Ulrich Humpf
• 金额: --
• 依托单位: Institut für Lebensmittelchemie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2012
• 资助国家: 德国
• 起止时间: 2011-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/227350539?language=en
• 关键词: Biosynthetic; toxic; potential; ergot; Biological

Claviceps purpurea is a plant pathogenic fungus which is well known for the production of toxic ergot alkaloids. Besides this not much is known about the production of other secondary metabolites. In the first funding period two secondary metabolite gene clusters were characterized in detail in C. purpurea. The first cluster with a nonreducing polyketide synthase as key enzyme (PKS4) was identified as the ergochrome gene cluster responsible for the production of pigments. The second identified cluster with a nonribosomal peptide synthetase as key enzyme (NRPS3) shows homology to clusters encoding epipolythiodiketopiperazine (ETP) toxins characterized by a diketopiperazine ring with an internal disulfide-bridge. Unexpectedly, no molecules with the typical ETP structures could be detected. Instead, several intermediates with an unusual nitrogen-sulfur bond were identified. The overexpression of a cytochrome P450 oxidase from the ETP cluster in Leptospaeria revealed new compounds, named clapurines, with the typical ETP structure.Goal of this proposal is (1) the detailed characterization of further new secondary metabolite gene clusters with so far unknown function in C. purpurea using a genome mining approach and the structure elucidation of the biosynthetic endproducts, (2) to elucidate the detailed mechanism for the formation of the newly identified clapurines as well as the metabolites of the ETP-like gene cluster with the unusual N-S moiety, (3) to study the cytotoxicity of all new secondary metabolites of C. purpurea as these metabolites might play a role as food contaminants and (4) to characterize so far unknown pigments produced also under stress conditions and to elucidate their biosynthetic pathway.

麦角菌是一种植物病原真菌，其以产生毒性麦角生物碱而闻名。除此之外，对其他次级代谢产物的产生知之甚少。在第一个资助期，在C.紫花。第一个簇与非还原聚酮合成酶作为关键酶（PKS 4）被确定为麦角色素基因簇负责生产的色素。第二个确定的集群与非核糖体肽合成酶作为关键酶（NRPS 3）显示同源性的集群编码epipolithiodiketopiperazine（ETP）毒素的特点是一个二酮哌嗪环与内部二硫桥。出乎意料的是，没有检测到具有典型ETP结构的分子。相反，鉴定出几种具有不寻常的氮-硫键的中间体。本研究的目的是（1）进一步研究新的次生代谢产物基因簇，并对这些基因簇的功能进行详细的鉴定。（2）阐明新鉴定的红毛菊嘌呤类化合物以及带有不寻常的N-S基团的类ETP基因簇的代谢产物的详细形成机制;（3）研究红毛菊所有新的次级代谢产物的细胞毒性。这些代谢物可能作为食品污染物发挥作用;（4）表征迄今为止在胁迫条件下产生的未知色素，并阐明其生物合成途径。