New Biologically Active Natural Products from Fungi

描述（由申请人提供）：本申请要求支持一个项目，该项目将从几个选定的环境生态位群中分离真菌，作为新的生物活性天然产物的来源进行探索。该项目将采用一种独特的基于生态学和分类学的方法来进行生物选择，这与传统的随机微生物筛选项目有很大的不同。研究目标真菌包括从淡水、真菌、粪菌、生菌核和内生群落分离的真菌。这些生态系统的选择基于多种考虑，包括物种间对抗的高发生率，形态，分类和生态独特性，以及生产力的记录。基于对对抗机会性真菌感染的新治疗方法的日益增长的需求，在内部的努力将集中在寻找新的抗真菌代谢物。提取物和化合物也将通过NCI发育治疗项目筛选技术部门的安排进行其他活动的测试。该计划由Prs小组与世界上最重要的水生真菌学专家之一C.A. Shearer教授合作进行。我的同事D.T.威克洛博士在真菌学的其他方面拥有丰富的专业知识，他也将参加。在美国国立卫生研究院和其他来源的支持下，对这些生态系统中分离物的研究已经提供了各种新的生物活性剂，包括许多具有新颖结构的生物活性剂。这些结果提供了强有力的证据，证明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。有许多分离物和提取物可供立即研究。在许多情况下，没有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进行生物测定，以优先考虑它们的研究。活性成分将通过生物测定引导分离分离，其结构将使用光谱方法确定。随着化学研究的进展，进一步的物种将被分离和筛选，从而为研究提供源源不断的新分离物。

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.