Omics approaches for natural products discovery

描述（由申请人提供）：该提案旨在开发天然产物发现的新方法。虽然已经在设计药物样合成筛选文库上投入了很多努力，但是在提高命中的新奇和增加文库内的药物样或铅样结构方面，已经进行了有限的努力来逻辑地设计天然产物筛选文库。这个项目将评估逻辑自然产品库设计， 高通量筛查的结果，主要是在肿瘤学和传染病领域。特别是，我们将应用基于LCMS的非靶向代谢组学来帮助指导文库设计。我们将使用代谢组学、基因组学、转录组学和蛋白质组学来研究物种间的相互作用。了解物种间相互作用和次级代谢产物产生的系统生物学将揭示激活神秘簇的新机制。这一提议的成果将是：（i）产生富含具有药物样特性的新/新型小分子的天然产物库的模板;和（ii）快速确定物种间相互作用改变次级代谢产物产生的生物体的平台。

DESCRIPTION (provided by applicant): The proposal aims to develop new approaches to natural products discovery. While much effort has been placed on designing drug-like synthetic screening libraries, limited efforts have been put forth to logically design natural product screening libraries in terms of improving novelty of hits and increasing drug-like or lead-like structures within the library. This project will evaluate logical natural product library design on the outcome of high-throughput screening, primarily in the areas of oncology and infectious disease. In particular, we will apply LCMS-based untargeted metabolomics to help guide library design. We will use metabolomics, genomics, transcriptomics, and proteomics to investigate interspecies interactions. Understanding the systems biology governing interspecies interactions and secondary metabolite production will uncover new mechanisms to activate cryptic clusters. The outcomes of this proposal will be: (i) a template for producing natural product libraries enriched in new/novel small molecules with drug-like properties; and (ii) a platform for rapidly determining organisms where interspecies interactions change secondary metabolite production.