COPROPHILOUS FUNGI--NEW SOURCES OF BIOACTIVE METABOLITES

该提案要求提供支持以修改和扩展正在进行的 益生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、形态和 在分类上有区别，它们通常表现出拮抗作用 对抗Ohter真菌。我们从这些化合物中寻找抗真菌代谢物 物种是基于系统的、基于生态学的方法来研究微生物体的 代表着与传统随机微生物的背离的选择 筛选计划。各种新的抗真菌药物，包括许多 具有不同寻常的化学结构，在这个项目中被分离出来 通过生物测定指导的共生真菌的化学研究。我们的结果 提供令人信服的证据表明这些真菌显示出相当大的前景 新型天然抗真菌产品的来源。因为越来越多的 迫切需要有效对抗机会性真菌的新疗法 在人类感染中，筛查努力将专门专注于搜索 对于具有抗医学相关真菌活性的新代谢物。纯正 化合物最终将被用于其他活性测试，具有很高的 优先考虑与癌症相关的检测。 许多额外的菌株对真菌具有抗真菌作用 直接竞争分析中的机会性真菌病原体是可用的 用于研究，而这些都没有被化学研究过。这些 分离株将在液体和单一基质下培养。 发酵条件，这些发酵的萃取物将是 与一组医学真菌分离株进行测试，以确定培养的优先顺序 用于化学研究。抗真菌成分将通过以下途径分离 生物测定引导的分离，它们的结构将用 最先进的光谱技术。虽然化学研究是 在进展中，将分离、鉴定和鉴定更多的共生物种 在马洛赫教授的实验室里进行了抗真菌活性的筛选 这是一位真菌共生领域的专家。三年取得的进展 到目前为止，这个项目证明了研究团队有能力 进行拟议的研究，并强调需要继续 对这一相对未被开发的潜在有价值来源的调查 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.