Project 2: Aquatic Cyanobacteria Plant Collections

本计划项目提案的总体目标是发现可以作为 抗癌药物的来源多种多样。项目2，位于药学院，大学 伊利诺伊州芝加哥大学（UIC），是由植物，化学和生物元素。的主要目标 项目二是从蓝藻中发现新的抗癌先导化合物，并为热带植物提供 项目1的材料，位于俄亥俄州州立大学（OSU）。项目2的基本假设 从培养的非海洋蓝细菌和热带植物中获得的多种天然产物结构 将是抗癌药物的丰富来源为实现既定目标，项目2的具体目标如下 如下：1）获得、培养、提取和制备蓝藻菌株的级分，并测序 所选菌株的基因组。我们每年将获得100株蓝藻菌株。菌株收集将 重点关注在美国上中西部和五大湖地区采集的样本。将培养每种菌株， 提取、分离并提供用于核心1可用生物试验系统中的生物学评价 和项目1以及我们的外部生物测定供应商。作为一种补充和综合办法，我们 每年将对20个菌株进行测序和基因组挖掘，并选择菌株进行测序 基于a）有希望的生物活性;和B）基于化学分类学或PCR筛选的优先化。2)到 分离和确定活性蓝藻代谢产物的结构，提高铅的产率 化合物.将使用活性监测分馏对显示有希望活性的提取物进行分馏， 获得纯天然产物。结构特征的活性分离株将在 生物学测试系统。我们将重新分离出大量的候选化合物。 为了提高产量，必要时，我们将评估不同的栽培条件，并探索 先导化合物的生物合成基因簇的异源表达，这将有助于提供一种 生产的替代来源。3)获得所有的植物材料，这将是所需的拟议 计划项目。我们每年将从选定的植物中获得150个有充分记录和鉴定的植物样本。 世界各国。干燥和研磨的植物材料将提供给项目1进行进一步加工。 我们还将重新收集植物材料，以便更大规模地分离需要更详细研究的活性化合物。 根据需要进行生物学评价。

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.