BAC Sudoku Sequencing Paradigm to Accelerate Metagenomic Natural Product Chemistr

BAC 数独测序范式加速宏基因组天然产物化学研究

基本信息

批准号：
8712292
负责人：
MARK R LILES
金额：
$ 21.38万
依托单位：
LUCIGEN CORPORATION
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-06-01 至 2015-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8712292
关键词：
American Anti-Infective Agents Antibiotic Resistance Antibiotics Bacteria Bacterial Artificial Chromosomes Biodiversity Bioinformatics Biological Assay Biological Factors Businesses Chemicals Clinical Cloning Communicable Diseases Complex Computer Simulation Computer software DNA Data Development Environment Genes Genetic Genome Goals Growth Human Infection Lead Libraries Life Massive Parallel Sequencing Medical Metagenomics Methods Natural Products Chemistry Nutritional Outcomes Research Partner in relationship Pathway interactions Pharmaceutical Preparations Phase Process Production Public Health Research Research Proposals Resistance Resources Sampling Science Scientist Sequence Analysis Services Site Small Business Innovation Research Grant Soil Source Technology Testing Therapeutic Time Universities Work antimicrobial base combinatorial design drug discovery fight against high throughput technology improved innovation methicillin resistant Staphylococcus aureus microbial microbial community next generation next generation sequencing novel pathogen public health relevance screening small molecule small molecule libraries tool

项目摘要

DESCRIPTION (provided by applicant): There is societal need for new compounds in our arsenal of defenses against microbial pathogens, many of which are increasingly resistant to existing therapeutics. The best possible source for new antimicrobial compounds with potentially novel mechanisms of action is within natural environments, particularly soils, which have the greatest diversity of microbial life. This research proposal advances the science of metagenomics, the cloning of DNA from entire microbial communities, to discover novel antibiotics and identify the best lead candidates for clinical development. Scientists at Lucigen Corporation and Auburn University have combined key technological breakthroughs that result in an improved paradigm for screening metagenomic libraries for small molecules. A major rate limiting step in this process is the millions of bioassays required to screen natural product libraries for small molecules with bioactivity. This Phase I SBIR will develop new tools for massively parallel next-generation sequencing and analysis of the metagenomic libraries to discover natural product pathways in silico. The process will accelerate natural product chemistry discovery fifty-fold while eliminating the bias of biological assays. The successful outcome of this research will also revolutionize the ability to completely analyze complex genomes of significant nutritional and medical value to humans.

描述（由申请人提供）：社会需要我们的防御微生物病原体库中的新化合物，其中许多病原体对现有疗法的抵抗力越来越强。具有潜在新颖作用机制的新型抗菌化合物的最佳来源是自然环境，特别是微生物生命多样性最丰富的土壤。这项研究提案推进了宏基因组学科学，即从整个微生物群落中克隆 DNA，以发现新型抗生素并确定临床开发的最佳先导候选药物。 Lucigen 公司和奥本大学的科学家结合了关键技术突破，改进了筛选小分子宏基因组文库的范例。该过程中的一个主要速率限制步骤是筛选具有生物活性的小分子的天然产物库所需的数百万次生物测定。第一阶段 SBIR 将开发新工具，用于大规模并行下一代测序和宏基因组文库分析，以在计算机中发现天然产物途径。该过程将加速天然产物化学发现五十倍，同时消除生物测定的偏差。这项研究的成功结果还将彻底改变对人类具有重要营养和医学价值的复杂基因组的分析能力。