COPROPHILOUS FUNGI--NEW SOURCES OF BIOACTIVE METABOLITES

通过对天然微生物的研究，发现了许多有用的药物。 产品。然而，共亲(粪便定植)真菌还没有 广泛研究次生代谢物的生产。两国之间的对立 共生真菌的种类一直是众多文献的主题 报告。造成这种影响的化合物基本上是天然的。 抗真菌药物，也可能显示出其他用途有用的生物活性。 我们认为共生真菌是一种潜在的有价值的来源。 具有药理活性的新天然产物。因此，我们 打算对选定的次生代谢物进行研究 共生真菌寻找具有抗真菌活性的新化合物， 抗生素、抗病毒药物、抗肿瘤药物和其他可能有用的药物 生物活动。 我们对此研究的方法是非随机的，因为它是基于 文献证据的运用与生态理性。共生的 为我们的研究选择的真菌种类将是那些已报道的 在对竞争对手表现出对抗效果的文献中，那些 它们出现在共生真菌演替的后期，而那些 与已经产生抗真菌作用的共生真菌密切相关 在我们的初步研究中。共生真菌的新鲜分离株 物种将通过分包合同、合作协议获得 与该大学的D.Malloch教授合作。是多伦多的，也是这一领域的专家 共生真菌学。培养滤液的标准化预筛选， 抗真菌和抗真菌的层析组分和纯化的代谢物 抗生素活动将在我们的实验室进行，一组 用于其他生物活性(抗病毒、抗真菌、抗肿瘤、 免疫调节剂等)将由一家合作的制药公司进行 公司(先灵公司)。内部抗真菌筛查将包括 针对天然竞争对手和与医学相关的真菌的测试。化验分析 代谢物对抗代谢物。初步结果表明， 我们选择的共生真菌分离物的百分比 筛查确实显示出抗真菌活性，几种抗真菌药物已经 通过这些初步调查被隔离。 这些研究与我们对真菌的长期兴趣密切相关 具有药理和生态意义的代谢物。相对的 对微生物生态系统的化学生态学知之甚少，尽管 微生物代谢物在现代医学中的重要性。通过我们的 在这方面的研究，我们期待着探索天然产物的化学 一个很少研究的真菌类，同时评估一个 以生态为基础的方法发现新的生物活性物质。

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.