COPROPHILOUS FUNGI--NEW SOURCES OF BIOACTIVE METABOLITES

该提案要求支持修改和扩大正在进行的 粪生真菌天然产物化学成分的研究 这些很少被研究的真菌在生态学、形态学和 分类学上有区别，它们通常表现出拮抗作用 对抗其他真菌 我们从这些植物中寻找抗真菌代谢物 物种是基于一个系统的，生态为基础的方法，以微生物 选择，代表了从传统的随机微生物 筛选程序。 各种新的抗真菌剂，包括许多 具有不寻常的化学结构，在这个项目中被分离出来 通过对粪生真菌的生物测定引导的化学研究。我们的结果 提供了令人信服的证据，这些真菌显示出相当大的希望， 新型抗真菌天然产物的来源。 因为越来越 迫切需要新的有效治疗机会性真菌 在人类感染，筛查工作将专门集中在搜索 寻找具有抗医学相关真菌活性的新代谢物。 纯 化合物最终将被测试其他活动，高 优先考虑癌症相关检测。 许多其他分离株表现出抗真菌作用， 直接竞争试验中的机会性真菌病原体是可用的 用于研究，这些都没有进行过化学研究。 这些 分离物将在液体和单一基质下培养 发酵条件，并且来自这些发酵的提取物将是 对一组医学真菌分离株进行了测试， 用于化学研究。 抗真菌成分将通过 生物测定引导的分馏，并且它们的结构将使用 最先进的光谱技术 虽然化学研究 在进行中，将进一步分离、鉴定和 在D.马洛赫河 粪生真菌学领域的专家。 取得的进展 到目前为止，该项目证明了研究团队的能力， 进行拟议的研究，并强调需要继续 对这一相对未开发的潜在价值资源的调查 天然产品。

This proposal requests support to modify and expand an ongoing investigation of the natural products chemsitry pf coprophilous fungi. These rarely-studied fungi are ecologically, morphologically and taxonomically distinctive, and they commonly display antagonistic effects against ohter fungi. Our search for antifungal metabolites from these species is based on a systematic, ecology-based approach to microrganism selection that represents a departure from traditional random microbial screening programs. A variety of new antifungal agents, including many with unusual chemical structures, have been isolated in this project through bioassay-guided chemical studies of coprophilous fungi. OUr results provide compelling evidence that these fungi show considerable promise as sources of novel anifungal natual products. Because of the increasingly urgent need for the new treatment effective against opportunistic fungal infection in humans, screening efforst will focus exclusively on searches for new metabolites with activity against medically relevant fungi. Pure compounds will ultimately be tested for other activities, with high priority assigned to cancer-relevant assays. Many additional isolates that exhibit anitfungal effects against opportunistic fungal pathogens in direct competition assays are available for investigation, and none of these have been studied chemically. THese isolates will be cultivated under both liquid and sole-substrate fermentation conditions, and the extracts frm these fermentations will be tested against a panel of medical fungal isolates to prioritize cultures for chemical studies. Antifungal components will be isolated through bioassay-guided fractionation, and their structures will determined using state-of -of-the-art spectroscopic techniques. While chemical studies are in progress, further coprophilous species will be isolated,identified, and screened for antifungal activity in laboratory of Prof. D. Malloch, an expert in thea field of coprophilous mycology. The progress achieved in this project thus far demonstrates the ability of the research team to perform the proposed studies, and underscores the need for continiued investigation of this relatively unexplored source of potentially valuable natural products.