Omics approaches for natural products discovery

描述(由申请者提供)：该提案旨在开发发现天然产品的新方法。虽然在设计类药物合成筛选文库方面付出了大量的努力，但在提高HITS的新颖性和增加文库中的类药物或类铅结构方面，对合理设计天然产物筛选文库的努力有限。该项目将对逻辑天然产物库设计进行评估 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。了解支配物种间相互作用和次生代谢物产生的系统生物学将揭示激活隐蔽簇的新机制。这一提议的结果将是：(I)建立一个模板，用于生产富含新的/新颖的具有药物性质的小分子的天然产物库；以及(Ii)一个快速确定物种间相互作用改变次生代谢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.