Natural Products from Under-explored Microorganisms

来自未充分探索的微生物的天然产物

• 批准号: 8066411
• 负责人: Ben Shen
• 金额: $ 37.12万
• 依托单位: SCRIPPS FLORIDA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8066411
• 关键词: Actinobacteria class; Bacteria; Biochemical; Biodiversity; Biological Assay; Biological Factors; Biology; Chemicals; China; Chinese People; Detection; Fermentation; Health; High Pressure Liquid Chromatography; Human; Institutes; Libraries; Medicinal Plants; Microbiology; Molecular Bank; Pharmaceutical Preparations; Preparation; Process; Production; Screening procedure; Structure; Symbiosis; Universities; base; blind; member; microbial; microorganism; novel; public health relevance; scale up; tool

DESCRIPTION (provided by applicant): We propose to isolate novel natural products from under-explored microorganisms and provide them to the Molecular Libraries Screening Center Network (MLSCN). The bacterial strains that will be investigated include: (i) endophytes, (ii) actinomycetes, and (iii) extremophiles from under-explored ecological niches in various parts of China. The criteria for strain selection are: (i) the uniqueness and richness of biodiversity, (ii) symbiosis with traditional Chinese medicinal plants, (iii) morphological and taxonomical distinctiveness, and (iv) bias towards actinomycetes. We will (i) optimize natural product production, (ii) prepare extracts and subject them to TLC and HPLC for chemical profiling and titer estimation followed by LC-MS and 1H NMR dereprelication for strain prioritization, (iii) isolate and determine the structures of the novel natural products, and (iv) provide them to MLSCN. Our hypotheses are: (i) bacteria that are morphologically distinctive and taxonomically new are likely to produce novel natural products, (ii) assay-blind and TLC- and HPLC-based chemical profilings allow the detection of all natural products, (iii) LC-MS and 1H NMR followup analyses permit rapid dereplication of the extracts, allowing prioritization of the strains for subsequent isolation and structural elucidation, and (iv) quantities of the natural products can be produced by scaleup microbial fermentation. The specific alms are: (i) to evaluate 600 strains, including approximately 200 endophytes, 300 actinomycetes, and 100 extremophiles, provided by Prof. Cheng-Lin Jiang of the Yunnan Institute of Microbiology, Yunnan University, China, by fermentation optimization, extract preparation, TLC- and HPLC-based chemical profiling and titer estimation, and LC-MS and 1H NMR analyses to identify 15 hit strains annually; (ii) to dereplicate the natural products in the 15 hit strains by natural product isolation and structural elucidation to identify one to five novel natural products per strain to yield a total of 15-75 compounds annually; and (iii) to scale up fermentation of the hit strains and to provide a 15-75-member library of the resultant novel natural products, each of which will be HPLC and NMR pure and in quantities weighing minimally 10 mg, to MLSCN annually. PUBLIC HEALTH RELEVANCE: Natural products have inspired ~75% of the drugs approved for human use and are evolutionarily optimized to serve as modulators of biologically important processes. This application seeks to discover natural products from new microorganisms, isolated from previously untapped and carefully selected ecological niches, for use as biochemical tools by which to understand fundamental and applied biology.

描述（由申请人提供）：我们建议将新型天然产物与未经探索的微生物分离，并将其提供给分子库筛选中心网络（MLSCN）。将研究的细菌菌株包括：（i）内生菌，（ii）放线菌和（iii）来自中国各地的未经探索的生态壁ni的极端细胞。选择应变的标准是：（i）生物多样性的独特性和丰富性，（ii）与传统的中国药用植物共生，（iii）形态学和分类学的独特性，以及（iv）偏向于放线症。我们将（i）优化天然产物的生产，（ii）准备提取物，并使它们接受TLC和HPLC的化学分析和滴度估计，然后进行LC-MS和1H NMR效应，以菌株优先次序（III）分离株，并确定新型天然产物的结构，并（IV）提供给MLSCN。我们的假设是：（i）在形态上具有独特性和分类性新的细菌可能产生新型的天然产物，（ii）基于盲目的和TLC和HPLC和HPLC的化学探索允许检测所有天然产物，（III）LC-MS和1H NMR随访允许快速消除允许的优先级别，隔离范围，并隔离构造，并隔离效果，并进行了隔离效果，并划分了划分的效果，并可以隔离效果，并有效地分散效应，并可以隔离效果，并可以隔离效果，并可以隔离效果分析，并可以隔离效果分析，并可以隔离效果分析，并可以隔离效果分析，并可以隔离效果。 （iv）天然产物的数量可以通过比例微生物发酵产生。具体的施舍是：（i）评估600种菌株，包括大约200个内生菌，300个活化菌和100个极端噬菌体，由中国云南微生物学研究所的Cheng-lin Procs提供，通过发酵优化，TLC-基于TLC-and tlc-and trc-nm and toter and toter and toter and toter和TRC的化学分析，以及1个Yunnan微生物学研究所。每年识别15个命中菌株； （ii）通过天然产物的隔离和结构阐明在15个命中菌株中删除天然产物，以鉴定每种菌株的一到五种新颖的天然产物，以每年产生15-75种化合物； （iii）缩放命中菌株的发酵，并提供15-75个成员的新颖天然产物的库，每种产品将是HPLC和NMR Pure，并且重量为10 mg，每年将重量为10 mg，每年都有MLSCN。 公共卫生相关性：天然产品激发了约75％的用于人类使用的药物，并在进化上优化了作为生物学上重要过程的调节剂。该应用程序旨在发现与以前未开发和精心挑选的生态壁ches分离的新微生物中的天然产品，以用作了解基本和应用生物学的生化工具。