基于NanoDESI-LTQ-FT质谱和小分子化合物网络快速鉴定微生物来源的抗结核活性成分

结核病是威胁人类健康的世界三大传染病之一，多药耐药结核（MDR-TB）和广泛耐药结核（XDR-TB）的不断出现使结核病再次回归公众视线。天然产物是抗结核药物研发的重要来源，其中来自于微生物的天然产物是其重要组成部分。我们在本实验室已经建立的来自于多种生态环境（深海、高原土壤、盐湖、火山以及中药内生菌）、高生物多样性的天然菌株库基础上，采用NanoDESI-LTQ-FT技术和MS/MS networking （二级质谱小分子网络），结合计算机统计分析技术，建立次级代谢产物小分子网络库，把不同结构类型的化合物列于不同的网络簇上，依此进行快速排重和鉴定新的活性化合物。NanoDESI技术简化了天然产物排重的繁琐步骤，而计算机科学协助我们无需数据库，直接高效进行海量数据的分析和归类。本课题中这一平台的建立和进一步完善，对快速发现和定位新结构的活性天然产物具有重要意义。

Tuberculosis (TB) is one of the world's three major infectious diseases that threaten human health, the continuous emergence of multi-drug resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) leads TB once again to be an important topic of global public health. Natural products are an important source of anti-TB drugs, part of which are from microbial sources. Hence, we intend to apply nanoDESI mass spectrometry, MS/MS networking and computer statistics analysis technology to analyze the secondary metabolites directly from the agar plates. The molecular networking generated based on MS2 pattern of secondary metablites will be used for the rapid de-replication of natural products.NanoDESI can simplify the procedures of de-replication, while computer science can directly analyze and classify the mass data without database. This proposal will develop a new approach for de-replication and rapid identification of active compounds from microbe, which is the most critical issue in the natural products drug discovery field.