The Chemistry of Fungal Antagonism and Defense

有了这个奖项，化学合成项目再次支持了爱荷华大学化学系的James B. Gloer教授的工作。Gloer教授和他的合作者，美国农业部的Patrick F. Dowd和Donald T. Wicklow，正在从真菌中分离出新的天然有机化合物。该项目将继续真菌天然产物化学的独特研究计划。主要重点将放在真菌/真菌真菌的化学研究，以及发生在谷类作物植物中的真菌内生菌。支寄生/真菌真菌攻击和殖民其他真菌在自然界中。这些殖民者的入侵通常涉及对宿主的抗生素，因此，这些殖民者可能是有价值的，未被开发的天然抗真菌剂的来源。先前国家科学基金会支持的结果为这一假设的有效性提供了强有力的证据。拟议拨款期间的工作将集中于完成对夏威夷岛上不同小气候中近800种不同真菌殖民者的研究。第二个方向是从发现广泛分布的玉米内生菌分离物产生各种类型的天然产物，这些产物对玉米植物中遇到的其他竞争真菌，包括重要的致病和产生真菌毒素的物种，表现出拮抗活性。对这些代谢物的发生和意义的研究将继续进行，并将扩大到包括来自其他作物植物（黑麦、小麦、大麦、高粱）和有限数量的草原草的真菌，以寻找显示类似生物效应和潜在意义的进一步代谢物。在这两个项目中，寻找新的化学物质是通过对两种重要真菌物种和/或一种重要农业害虫的活性测定来指导的。根据最近的一项发现，一种常见的玉米内生菌产生一种有效的Hsp90功能抑制剂，Hsp90活性测定也将包括在内。通过这些假设指导的研究，已经发现了许多新的生物活性天然产物，并且由于这些真菌群的相对未被探索的性质，预计将取得进一步的成功。抗真菌和抗虫剂在农业和医学方面具有潜在的实用价值，也可以作为辅助发现新的作用方式的工具。该项目的研究结果也有望为其他学科的基础科学知识做出贡献，包括真菌生态学、分类学、生物多样性、作物/食品科学和进化生物学。

With this award, the Chemical Synthesis Program is renewing support for the work of Professor James B. Gloer of the Department of Chemistry at the University of Iowa. With his collaborators, Patrick F. Dowd and Donald T. Wicklow of the U.S. Department of Agriculture, Professor Gloer is isolating new natural organic compounds from fungi. The project will continue this distinctive research program in fungal natural products chemistry. Primary focus will be placed on chemical studies of mycoparasitic/fungicolous fungi, and on fungal endophytes that occur in cereal crop plants. Mycoparasitic/fungicolous fungi attack and colonize other fungi in nature. Invasion by these colonists often involves antibiosis toward the host, and therefore, such colonists may be valuable, underexplored sources of natural antifungal agents. Results from prior NSF support provide strong evidence for the validity of this hypothesis. Efforts during the proposed grant period will focus on completion of the studies of a collection of nearly 800 diverse fungal colonists obtained from varied microclimates found on the island of Hawaii. A second direction follows from the discovery that isolates of widespread corn endophytes produce natural products of various types that show antagonistic activity against other, competing fungi encountered in corn plants, including important disease-causing and mycotoxin-producing species. Studies of the occurrence and significance of these metabolites will continue, and will be expanded to include fungi from other crop plants (rye, wheat, barley, sorghum), and a limited number of prairie grasses, in search of further metabolites that show similar biological effects and potential significance. In both projects, the search for new chemistry is guided by assays for activity against two important fungal species and/or an agriculturally important insect pest. An assay for Hsp90 activity will also be included based on a discovery in the most recent grant period that a common corn endophyte produces a potent inhibitor of Hsp90 function. Many new bioactive natural products have been discovered through these hypothesis-guided studies, and further success is expected because of the relatively unexplored nature of these fungal groups. Antifungal and antiinsectan agents are of potential practical value to society in agriculture and medicine, and can also be valuable as tools to assist in discovery of new modes of action. Findings from this project are also expected to contribute to fundamental scientific knowledge in other disciplines, including fungal ecology, taxonomy, biodiversity, crop/food science, and evolutionary biology.