Discovery of Anti-Bioweapon Agents in BAC Libraries

描述（由申请人提供）：抗生素是生物防御准备的重要组成部分。土壤微生物是世纪抗生素的主要来源，但抗生素的发现现在受到严重限制。一个主要原因是，从微生物中发现的药物仅限于那些可以通过实验室培养回收的微生物，从而产生了很高的抗生素再发现率。 eMetagen的开创性技术，直接克隆微生物基因组DNA从土壤中将被用来发现新的抗生素针对NIAID A类和B类生物防御病原体。抗生素生物合成途径通常包含许多基因，因此eMetagen的克隆大DNA片段的技术对抗生素发现至关重要。创新的方法将用于构建大基因组DNA插入文库（目标1），该文库将以阵列形式筛选编码新聚酮抗生素的基因（目标2）。eMetagen文库还将筛选对生物武器替代物具有活性的新型广谱抗生素（Aim 3）。 知识产权将包括改进的eMetagen文库、阵列文库、发现的抗生素的化学结构以及编码其合成的基因。在第二阶段，eMetagen将充分表征第一阶段发现的聚酮化合物和其他抗生素，并与制药公司和政府实验室合作，推进产品开发。

DESCRIPTION (provided by applicant): Antibiotics are an essential component in bio-defense preparedness. Soil microorganisms were a major source of antibiotics during the 20th century, yet antibiotic discovery is now severely limited. A primary reason is that drug discovery from microorganisms has been confined to those microbes that can be recovered by laboratory cultivation, yielding high rates of antibiotic rediscovery. eMetagen's pioneering technology for the direct cloning of microbial genomic DNA from soils will be used to discover new antibiotics targeting NIAID category A and B bio-defense pathogens. Antibiotic biosynthesis pathways typically contain many genes therefore eMetagen's technology for cloning large DNA fragments is critical for antibiotic discovery. Innovative approaches will be used for the construction of large-genomic-DNA-insert libraries (Aim 1) that will be screened in an array format for genes encoding new polyketide antibiotics (Aim 2). eMetagen libraries will also be screened for new classes of broad spectrum antibiotics with activity against bioweapon surrogates (Aim 3). Intellectual property will include the improved eMetagen libraries, the arrayed libraries, the chemical structures of discovered antibiotics and the genes encoding their synthesis. In Phase II, eMetagen will fully characterize polyketide and other antibiotics discovered in Phase I and partner with pharmaceutical companies and government laboratories to advance product development.