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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI027436-09
Application #
2886597
Study Section
Bio-Organic and Natural Products Chemistry Study Section (BNP)
Program Officer
Dixon (Dmid), Dennis M
Project Start
1990-06-01
Project End
2001-04-30
Budget Start
1999-05-01
Budget End
2001-04-30
Support Year
9
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Iowa
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
041294109
City
Iowa City
State
IA
Country
United States
Zip Code
52242
Che, Yongsheng; Gloer, James B; Koster, Brenda et al. (2002) Decipinin A and decipienolides A and B: new bioactive metabolites from the coprophilous fungus Podospora decipiens. J Nat Prod 65:916-9
Hein, S M; Gloer, J B; Koster, B et al. (2001) Bombardolides: new antifungal and antibacterial gamma-lactones from the coprophilous fungus Bombardioidea anartia. J Nat Prod 64:809-12
Che, Y; Swenson, D C; Gloer, J B et al. (2001) Pseudodestruxins A and B: new cyclic depsipeptides from the coprophilous fungus Nigrosabulum globosum. J Nat Prod 64:555-8
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Hein, S M; Gloer, J B; Koster, B et al. (1998) Arugosin F: a new antifungal metabolite from the coprophilous fungus Ascodesmis sphaerospora. J Nat Prod 61:1566-7
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Wang, Y; Gloer, J B; Scott, J A et al. (1995) Terezines A-D: new amino acid-derived bioactive metabolites from the coprophilous fungus Sporormiella teretispora. J Nat Prod 58:93-9
Alfatafta, A A; Gloer, J B; Scott, J A et al. (1994) Apiosporamide, a new antifungal agent from the coprophilous fungus Apiospora montagnei. J Nat Prod 57:1696-702
Wang, Y; Gloer, J B; Scott, J A et al. (1993) Appenolides A-C: three new antifungal furanones from the coprophilous fungus Podospora appendiculata. J Nat Prod 56:341-4