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Microbial Strain Prioritization Using Metabolomics Tools for the Discovery of Natural Products

机译:使用代谢组学工具发现天然产物的微生物菌株优先次序

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摘要

Natural products profoundly impact many research areas, including medicine, organic chemistry, and cell biology. However, discovery of new natural products suffers from a lack of high throughput analytical techniques capable of identifying structural novelty in the face of a high degree of chemical redundancy. Methods to select bacterial strains for drug discovery have historically been based on phenotypic qualities or genetic differences and have not been based on laboratory production of secondary metabolites. Therefore, untargeted LC/MS-based secondary metabolomics was evaluated to rapidly and efficiently analyze marine-derived bacterial natural products using LC/MS-principal component analysis (PCA). A major goal of this work was to demonstrate that LC/MS-PCA was effective for strain prioritization in a drug discovery program. As proof of concept, we evaluated LC/MS-PCA for strain selection to support drug discovery, for the discovery of unique natural products, and for rapid assessment of regulation of natural product production.
机译:天然产物深刻地影响了许多研究领域,包括医学,有机化学和细胞生物学。然而,新的天然产物的发现由于缺乏高通量分析技术而无法在面对高度化学冗余的情况下识别结构新颖性。历史上,选择用于细菌发现的细菌菌株的方法是基于表型质量或遗传差异,而不是基于实验室产生的次级代谢产物。因此,使用LC / MS主成分分析(PCA)对基于LC / MS的非靶向次级代谢组学进行了评估,以快速有效地分析海洋来源的细菌天然产物。这项工作的主要目的是证明LC / MS-PCA在药物发现程序中对菌株优先级排序有效。作为概念验证,我们评估了LC / MS-PCA的菌株选择以支持药物发现,独特天然产物的发现以及对天然产物生产的调节的快速评估。

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