COPROPHILOUS FUNGI--NEW SOURCES OF BIOACTIVE METABOLITES

通过对微生物天然产物的研究，已经发现了许多有用的药物。 产品. 然而，粪生真菌（粪定殖）还没有被发现。 被广泛研究用于次级代谢产物的生产。 对立 粪生真菌的种类一直是许多文献的主题 报道 造成这种影响的化合物基本上是天然的 抗真菌剂，其也可显示其它用途的有用生物活性。 我们认为粪生真菌是一种潜在的有价值的资源 具有药理活性的新天然产物。 所以我们 打算对选定的次级代谢物进行研究 嗜粪真菌寻找具有抗真菌作用的新化合物， 抗生素、抗病毒、抗肿瘤和其它潜在有用的 生物活性 我们的研究方法是非随机的，因为它是基于 运用文献证据和生态理性。 粪生 我们的研究选择的真菌物种将是那些已经报道过的 在文献中，对竞争对手表现出拮抗作用， 在粪生真菌演替中出现较晚， 与已经产生抗真菌作用的粪生真菌密切相关 在我们的初步研究中。 粪生真菌的新鲜分离物 物种将通过分包、合作协议获得 与D教授他是多伦多大学的马洛赫， 粪生真菌学 标准化的培养物预筛选， 层析组分和纯化的抗真菌代谢物， 抗生素活动将在我们的实验室进行，并进行一系列 其他生物活性（抗病毒、抗真菌、抗肿瘤， 免疫调节等）将由一家合作的制药公司 公司（Schering Corporation） 内部抗真菌筛选将包括 针对天然竞争对手和医学相关真菌的测试。 的测定 代谢物对抗代谢物。 初步结果表明， 我们选择的粪生真菌分离株的百分比， 筛选显示抗真菌活性，几种抗真菌剂 通过这些初步调查被分离出来。 这些研究与我们对真菌的长期兴趣密切相关。 具有药理学和生态学意义的代谢物。 相对 尽管人们对微生物生态系统的化学生态学知之甚少， 微生物代谢物在现代医学中的重要性。 通过我们 在这方面的研究，我们希望探索天然产物化学 一个很少研究真菌类，而评估的潜力， 生态为基础的方法来发现新的生物活性剂。

Many useful drugs have been discovered through studies of microbial natural products. However, coprophilous (dung-colonizing) fungi have not been widely studied for secondary metabolite production. Antagonism between species of coprophilous fungi has been the subject of numerous literature reports. Compounds responsible for such effects are essentially natural antifungal agents, which may also exhibit other use useful bioactivities. We propose that coprophilous fungi comprise a potentially valuable source of new natural products with pharmacological activity. Therefore, we intend to undertake studies of the secondary metabolites of selected coprophilous fungi in search of novel compounds with antifungal, antibiotic, antiviral, antitumor, and other potentially useful bioactivities. Our approach to this research in non-random, since it is based on the application of literature evidence and ecological rational. Coprophilous fungal species chosen for our study will be those which have been reported in the literature to exhibit antagonistic effects toward competitors, those which occur late in coprophilous fungal successions, and those which are closely related to coprophilous fungi that have already yielded antifungal agents in our preliminary studies. Fresh isolates of coprophilous fungal species will be obtained through a subcontractual, collaborative agreement with Prof. D. Malloch of the Univ. of Toronto, and expert in the field of coprophilous mycology. Standardized prescreens of culture filtrates, chromatographic fractions, and purified metabolites for antifungal and antibiotic activities will be conducted in our laboratory, and a battery of 25 screens for other bioactivities (antiviral, antifungal, antitumor, immunomodulatory, etc.) will be conducted by a cooperating pharmaceutical company (Schering Corporation). In-house antifungal screens will include tests against natural competitors and medically relevant fungi. Assays of metabolites against metabolites. Initial results indicate that a high percentage of the coprophilous fungal isolates that we have chosen to screen do exhibit antifungal activity, and several antifungal agents have been isolated through these preliminary investigations. These studies are closely aligned with our long-term interest in fungal metabolites of pharmacological and ecological significance. Relatively little is known of the chemical ecology of microbial ecosystems, despite the importance of microbial metabolites in modern medicine. Through our studies in this area, we expect to explore the natural products chemistry of a seldom-studies fungal class, while evaluating the potential of an ecologically-based approach to the discovery of novel bioactive agents.