Exploiting Microbial Diversity for Natural Product Discovery

利用微生物多样性来发现天然产品

• 批准号: 8785212
• 负责人: PAUL R JENSEN
• 金额: $ 14.3万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8785212
• 关键词: Actinobacteria class; Address; Algae; Anabolism; Antibiotics; Artemia; Bacteria; Bacterial Genome; Biodiversity; Bioinformatics; Biological; Biological Assay; Biological Factors; Biological Testing; Chemicals; Classification; Coculture Techniques; Collaborations; Collection; Communicable Diseases; Communities; Complex; Country; Coupled; Custom; Data; Development; Disease; Evaluation; Fermentation; Fiji; Foundations; Funding; Gene Expression; Gene Expression Profile; Generations; Genes; Genome; Genomics; Geographic Locations; Habitats; Housing; Institutes; Ions; Joints; Lead; Libraries; Link; Location; Malignant Neoplasms; Marines; Mass Spectrum Analysis; Metabolism; Methods; Microbiology; Mining; Molecular; Natural Products Chemistry; Nutrient; Online Systems; Orphan; Pathway interactions; Phylogenetic Analysis; Phylogeny; Physiologic pulse; Porifera; Postdoctoral Fellow; Process; Production; RNA Sequences; Research; Resources; Running; Sampling; Scientist; Sequence Analysis; Solomon Islands; Staining method; Stains; Stimulus; Structure; Surface; System; Taxon; Taxonomy; Techniques; Technology Transfer; Training; Transcription Factor AP-1; Transcription Factor AP-2 Alpha; Trees; Tropical Disease; Universities; Visual; Work; abstracting; analytical tool; ascidian; base; design; drug candidate; drug discovery; genome sequencing; graduate student; improved; insight; meetings; microbial; microbial community; microorganism culture; neglect; nervous system disorder; novel; novel strategies; pre-clinical; programs; rapid technique; research clinical testing; scale up; screening; small molecule; tool; transcriptomics; web site

AP1: Exploiting Microbial Diversity for Natural Product Discovery Project Summary/Abstract The primary objective of the proposed research is to discover new, small molecule drug candidates from marine microorganisms cultured from Fiji and the Solomon Islands. This objective will be facilitated through the continued development of a productive microbial drug discovery program at the University of the South Pacific. Bioassays targeting cancer, infectious disease, neurological disorders, and neglected tropical diseases will be used to guide the isolation of compounds relevant to these targets. The structures of new compounds will be solved using modern spectral analyses and produced in sufficient quantities for effective pre-clinical evaluation. The research will target chemically rich microbial taxa including the marine actinomycete genus Salinispora and explore the relationships between biotic diversity and natural product discovery. The research benefits from a wealth of genome sequence data that has been acquired through the Joint Genome Institutes Community Sequencing Program. Bioinformatic analyses will be used to prioritize strains for chemical evaluation and to establish relationships between secondary metabolite biosynthetic potential, taxonomy, and the habitats and locations from which the stains originate. This information will be used to develop more effective sampling strategies and to provide new insight into the extant biosynthetic potential of marine bacteria and the evolutionary processes that generate structural diversity. Genome mining approaches will be used to link molecules to the pathways responsible for their production and to facilitate discovery and de-replication. The web-based tool NaPDoS (Natural Product Domain Seeker), which simplifies the analysis of genes involved with secondary metabolite biosynthesis, will be further developed to include additional pathway types and reference sequences. New cultivation methods will be developed that mimic natural conditions and provide ecologically relevant stimuli in an effort to induce secondary metabolite production. These studies will be coupled with transcriptome analyses, which will be used to determine the effects of culture conditions on biosynthetic gene expression. Highly sensitive methods in mass spectrometry will be used to better visual the secondary metabolome and generate networks that can be used to recognize new molecules, de-replicate known compounds, and search for correlations between geographic origin, phylogeny, and secondary metabolite production. Extensive post-doctoral, graduate, and undergraduate training will be provided throughout the program including training for host country scientists. Ultimately, this program aims to develop improved methods for natural product discovery and apply these approaches to the microbial resources in Fiji and the Solomon Islands in an effort to discover new drug candidates to treat diseases relevant to the US and the host nations.

AP1：利用微生物多样性来发现自然产品 项目摘要/摘要 拟议的研究的主要目的是从 从斐济和所罗门群岛培养的海洋微生物。这个目标将通过 南方大学的一项生产性微生物药物发现计划的持续开发 太平洋。靶向癌症，传染病，神经系统疾病和被忽视的热带的生物测定 疾病将用于指导与这些靶标相关的化合物的隔离。新结构 化合物将使用现代光谱分析来解决，并以足够数量的有效生产 临床前评估。该研究将针对包括海洋在内的化学丰富的微生物分类单元 放线菌属盐盐并探索生物多样性与天然产物之间的关系 发现。该研究受益于通过大量基因组序列数据获得的。 联合基因组机构社区测序计划。生物信息学分析将用于优先级 用于化学评估的菌株并在次级代谢物生物合成之间建立关系 潜在的，分类法以及污渍起源的栖息地和位置。这些信息将是 用于制定更有效的抽样策略，并提供有关现存生物合成的新见解 海洋细菌的潜力和产生结构多样性的进化过程。基因组开采 方法将用于将分子与负责生产的途径联系起来并促进 发现和恢复。基于Web的工具NAPDOS（自然产品域寻求者），简化了 对二级代谢产物生物合成涉及的基因的分析将进一步开发，以包括 其他途径类型和参考序列。将开发出新的耕种方法 自然条件并提供与生态相关的刺激，以诱导次级代谢物 生产。这些研究将与转录组分析相结合，该分析将用于确定 培养条件对生物合成基因表达的影响。高度敏感的质谱法 将用于更好地视觉视觉辅助代谢组，并生成可用于识别的网络 新分子，重复制的已知化合物以及地理起源之间的相关性， 系统发育和继发代谢产物。大量博士后，毕业生和本科生 在整个计划中将提供培训，包括对东道国科学家的培训。最终，这个 计划旨在开发改进的自然产品发现方法，并将这些方法应用于 斐济和所罗门群岛的微生物资源，以发现新的毒品候选者来治疗 与美国和东道国有关的疾病。