New Biologically Active Natural Products from Fungi

描述（由申请人提供）：本申请要求支持一项计划，其中将从几个选定的环境利基群体中分离出的真菌作为新的生物活性天然产物的来源进行探索。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、粪生、产生菌核和内生菌群落的分离株。选择这些生态系统是基于各种考虑，包括种间拮抗作用的高发生率，形态，分类和生态独特性，以及生产力的跟踪记录。基于对新治疗方法的需求日益增加，以对抗机会性真菌感染，内部工作将集中在寻找新的抗真菌代谢物上。通过与NCI开发治疗项目筛选技术分支的安排，还将对浸提液和化合物进行其他活性测试。拟议的项目涉及公关小组和C.A.教授之间的合作。世界上最重要的水生真菌学专家之一。D.T.医生威克洛，一个在真菌学其他方面具有广泛和互补专业知识的同事，也将参加。在NIH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。许多分离物和提取物可供立即研究。在许多情况下，没有文献报告相应生物的先前化学研究。将对单个真菌分离株的固体基质发酵培养物的提取物进行生物测定，以确定研究的优先顺序。活性成分将通过生物测定指导的分馏分离，并使用光谱方法确定其结构。随着化学研究的进展，将分离和筛选更多的物种，从而为研究提供一系列新的分离物。

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.