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.
Normal 0 false false false EN-US X-NONE X-NONE Our results have demonstrated that fungi that attack and colonize or parasitize others in nature tend to produce natural antifungal chemicals that may be involved in such processes. These chemicals are often new to science, and frequently have intriguing properties that pose distinctive challenges in purification or in complete determination of their chemical structures. Many such findings have emerged from this project during the grant period. Ongoing needs for such biologically active agents in both agriculture and medicine suggest that some of these discoveries may have practical importance. Similarly, we find that certain fungi that colonize corn or other crop plants also sometimes produce natural chemicals that are effective against other microbes that cause plant diseases, or against insects that may attack plant hosts. Results like these can provide fundamental insights into fungal life cycles and disease processes, and offer valuable clues that can lead to the discovery of additional new natural chemicals with potentially useful effects. In another vein, knowledge gleaned in this project about the chemistry associated with a widespread fungal endophyte/disease agent of corn, and detection of these metabolites in field-plot corn samples, may prove to be of broad impact and significance in a variety of areas, ranging from plant pathology to agriculture and food science. Our results and the expertise we have developed through this kind of work have led to many collaborations with scientists in neighboring disciplines, resulting in a wide variety of contributions that reflect the broader impact of this program in different ways. Such contributions range from identification of new natural chemicals in peanut plants that may help protect them from microbial diseases, to discovery of the first fungal metabolites reported to be active against botulinum neurotoxin, to recognition and description of various new fungal species, to identification of metabolites formed in the environment from steroids commonly used in livestock production, and others. All of these elements offer excellent, diverse training opportunities for the students involved in the project. Four students completed their Ph.D. degrees and graduated with theses based in part on results obtained in this project during the grant period, and three others will soon follow. Further miscellaneous contributions to the community included depositing genetic sequence information for our fungal isolates in public databases, providing samples of rare natural chemicals to researchers at other institutions, and making these distinctive chemicals available to our campus high-throughput screening center to optimize chances for discoveries that could arise due to unexpected effects they might show.
