Ribosomal natural products from the human oral microbiome

来自人类口腔微生物组的核糖体天然产物

• 批准号: 236329749
• 负责人: Dr. Max Crüsemann
• 金额: --
• 依托单位: Institut für Pharmazeutische Biologie
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2013-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/236329749?language=en
• 关键词: Ribosomal; natural; products; human; oral

The project deals with the characterization of new natural products from the human oral microbiomeDuring the survey and characterization of the human microbiome a lot of bacterial genomes were sequenced. In the search for gene clusters for new natural products, in two genomes of members of the actinomycetales, several gene clusters encoding for different ribosomal synthezised natural products (lantipeptides, lasso peptides, linaridins) were found. The putative lasso peptide gene cluster shows unusual features: Up to twelve, but at least five precursor peptides are encoded next to each other, adjacent to a processing enzyme, an asparagine synthetase. This enzyme thus seems to have a great substrate promiscuity. In the course of this project, as many as possible of the up to 17 predicted natural products should be characterized and their structure elucidated. This should be done initially with mass spectrometric methods as Nano-DESI-MS. The Moore and Dorrestein labs have lots of experience with the mass-spectrometry based characterization of peptides combined with bioinformatic methods. Interesting candidates should be tested against different biological targets and their structure should be fully elucidated with NMR spectroscopy. Additionally, the putatively promiscuous asparagine synthetase should be further characterized and the promiscuity should be exploited, to synthesize new unnatural natural products. Another part of the project deals with the characterization of the symbioses of the human oral microbiome bacteria: The metabolic interactions of bacterial strains should be elucidated by cocultivations and subsequent MALDI imaging mass spectrometry and molecular networking analysis. Additionally, more of the sequenced genomes of the oral microbiome should be searched systematically for further natural product gene clusters and possibly missing biosynthetic pathways from the primary metabolism to further characterize the symbioses.

该项目涉及人类口腔微生物新的天然产物的特征。在对人类微生物群进行调查和特征描述期间，对大量细菌基因组进行了测序。在寻找新的天然产物基因簇的过程中，在放线菌目的两个基因组中，发现了编码不同核糖体合成的天然产物(多肽、套索肽、亚麻素)的基因簇。推测的套索多肽基因簇显示出不同寻常的特征：多达12个，但至少有5个前体多肽彼此相邻编码，毗邻加工酶，天冬酰胺合成酶。因此，这种酶似乎有很大的底物杂交性。在这个项目的过程中，应该尽可能多地对预测的17种天然产物进行表征，并阐明它们的结构。这应该首先用像Nano-Desi-MS这样的质谱学方法来完成。摩尔和多雷斯坦的实验室在结合生物信息学方法的基于质谱学的多肽表征方面拥有丰富的经验。感兴趣的候选化合物应该针对不同的生物目标进行测试，并且它们的结构应该通过核磁共振光谱得到充分的阐明。此外，还应进一步研究混杂天冬氨酸合成酶的性质，并对其加以利用，以合成新的非天然天然产物。该项目的另一部分涉及人类口腔微生物组细菌共生的特征：细菌菌株之间的代谢相互作用应通过共培养和随后的MALDI成像质谱仪和分子网络分析来阐明。此外，应该系统地搜索更多的口腔微生物组的测序基因组，以寻找更多的天然产物基因簇，以及可能缺少的初级代谢的生物合成途径，以进一步表征共生体。