New Biologically Active Natural Products from Fungi

描述(由申请人提供)：本申请请求支持一项计划，在该计划中，来自几个选定的环境生态位组的真菌分离株将作为新的生物活性天然产品的来源进行探索。该计划将采用一种独特的基于生态学和分类学的方法来选择生物体，这与传统的随机微生物筛选计划有很大的不同。调查的目标真菌包括来自淡水、真菌、共生真菌、产生菌核和内生植物群落的分离物。这些生态系统的选择是基于各种考虑，包括种间拮抗的高发生率、形态、分类学和生态独特性以及生产力的记录。基于对抗机会性真菌感染的新疗法的需求日益增加，公司内部的努力将集中在寻找新的抗真菌代谢物上。提取物和化合物也将通过与NCI发展治疗计划筛查技术分部的安排进行其他活动的测试。这项拟议的项目涉及PRS小组与世界最顶尖的水生真菌学专家之一C.A.希勒教授之间的合作。D·T·威克洛博士也将参加，他是一位在真菌学其他方面拥有广泛而丰富的专业知识的同事。在美国国立卫生研究院和其他来源的支持下，对这些生态系统的分离株的研究已经提供了各种新的生物活性物质，包括许多具有新结构的物质。这些结果提供了强有力的证据，证明了这种一般方法是有效的，并证明了研究团队执行拟议研究的能力。许多分离物和萃取物可供立即研究。在许多情况下，没有关于相应生物体的先前化学研究的文献报告。单个真菌分离物的固体底物发酵培养物的提取物将接受生物检测，以优先进行研究。活性成分将通过生物测定引导的分级分离出来，其结构将使用光谱方法确定。随着化学研究的进展，将分离和筛选更多的物种，从而为研究提供源源不断的新菌株。

DESCRIPTION (provided by applicant): This application requests support for a program in which fungal isolates from several selected environmental niche groups will be explored as sources of new bioactive natural products. This program will employ a unique ecology- and taxonomy-based approach to organism selection that represents a significant departure from traditional random microbial screening programs. Fungi targeted for investigation include isolates from freshwater, fungicolous, coprophilous, sclerotium-producing, and endophytic communities. These ecosystems have been chosen on the basis of a variety of considerations, including high incidence of interspecies antagonism, morphological, taxonomic, and ecological distinctiveness, and track record of productivity. Based on the increasing need for new treatments to combat opportunistic fungal infections, in house efforts will focus on a search for new antifungal metabolites. Extracts and compounds will also be tested for other activities through an arrangement with the Screening Technologies Branch of the NCI Developmental Therapeutics Program. The proposed project involves a collaboration between the Prs group and that of Prof. C.A. Shearer, one of the world's foremost experts in aquatic mycology. Dr. D.T. Wicklow, a colleague with extensive and complimentary expertise in other aspects of mycology, will also participate. With the aid of prior support from NIH and other sources, studies of isolates from these ecosystems have already afforded a variety of new bioactive agents, including many with novel structures. These results provide strong evidence that this general approach is effective, and demonstrate the ability of the research team to perform the proposed studies. Many isolates and extracts are available for immediate investigation. In many instances, there are no literature reports of prior chemical studies of the corresponding organisms. Extracts of solid-substrate fermentation cultures of individual fungal isolates will be subjected to biological assays to prioritize them for study. Active components will be isolated through bioassay-guided fractionation, and their structures will be determined using spectroscopic methods. While chemical studies progress, further species will be isolated and screened, thereby providing a continuing stream of new isolates for investigation.