Project 2: Aquatic Cyanobacteria Plant Collections

该计划项目建议书的首要目标是发现可用作 抗癌药物有多种天然来源。项目2，位于加州大学药学院 伊利诺伊州芝加哥分校(UIC)，由植物学、化学和生物元素组成。的主要目标是 项目2是从蓝藻中发现新的含铅抗癌化合物，并提供热带植物 项目1的材料，存放在俄亥俄州立大学(OSU)。项目2的基本假设 来自养殖的非海洋蓝藻和热带植物的多样化的天然产物结构 将成为抗癌线索的丰富来源。为实现所述目标，项目2的具体目标如下 1)蓝藻菌株的获取、培养、提取和制备，并进行测序 选定菌株的基因组。我们每年将获得100个蓝藻菌株。菌种收集将 重点关注在美国中西部北部和五大湖地区收集的样本。每种菌株都将进行培养， 在核心1提供的生物测试系统中提取、分级并提供生物评估 和Project 1以及我们生物检测的外部供应商。作为一种互补和综合的方法，我们 每年将对20个菌株的基因组进行测序和基因组挖掘，并将选择菌株进行测序 基于a)有希望的生物活性；以及b)基于化学分类或聚合酶链式反应筛选的优先顺序。2)至 分离和鉴定活性蓝藻代谢产物的结构，以提高铅的产量 化合物。表现出良好活性的提取物将使用活动监控分级法进行分级，以 获得纯天然产品(S)。这些具有结构特征的活性分离株将在 可供该计划使用的生物测试系统。我们将重新分离更多的候选化合物。 为了提高产量，在必要时，我们将评估不同的栽培条件，并探索 先导化合物生物合成基因簇的异源表达，这将有助于提供 生产的替代来源。3)获得拟议中的 计划项目。我们每年将从精选的植物中获得150个完整记录和识别的植物样本 世界各国。干燥和碾磨的植物材料将提供给项目1进行进一步处理。 我们还将重新收集植物材料，以便更大规模地分离活性化合物，需要更详细的 根据需要进行生物学评估。

The overarching goal of this Program Project proposal is to discover natural products that can serve as anticancer drug leads from diverse natural sources. Project 2, located at the College of Pharmacy, University of Illinois at Chicago (UIC), is comprised of botanical, chemical and biological elements. The primary goals for Project 2 are the discovery of new lead anticancer compounds from cyanobacteria and providing tropical plant material for Project 1, housed at The Ohio State University (OSU). The underlying hypothesis for Project 2 is that the diverse natural product structures from cultured non-marine cyanobacteria and tropical plants will be a rich source for anticancer leads. To achieve the stated goals the specific aims for Project 2 are as follows: 1) to obtain, culture, extract, and prepare fractions of cyanobacterial strains, and to sequence the genome of selected strains. We will obtain 100 cyanobacterial strains per year. The strain collection will focus on samples collected in the Upper Midwest and Great Lakes regions of the U.S. Each strain will be cultured, extracted, fractionated, and provided for biological evaluation in the biological test systems available at Core 1 and Project 1 as well as our external providers of bioassays. As a complementary and integrated approach, we will sequence and genome mine the genomes of 20 strains per year and strains will be selected for sequencing based on a) promising biological activity; and b) prioritization based on chemotaxonomy or PCR screen. 2) To isolate and determine the structures of active cyanobacterial metabolites, and to improve yields of lead compounds. Extracts showing promising activity will be fractionated using activity-monitored fractionation to obtain pure natural product(s). The structurally characterized, active isolates will be extensively evaluated in the biological test systems available to the program. We will re-isolate larger amounts of any candidate compound. In order to improve yields, when necessary, we will evaluate different cultivation conditions, and explore heterologous expression of the biosynthetic gene cluster of lead compounds, which will serve to provide an alternative source for production. 3) To acquire all plant materials that will be required by the proposed Program Project. We will obtain 150 fully documented and identified plant samples per year from selected countries of the world. The dried and milled plant material will be provided to Project 1 for further processing. We will also re-collect plant material for larger-scale isolation of active compounds requiring more detailed biological evaluation as needed.