Bioactive secondary metabolites from mycoparasitic, fungicolous, and freshwater fungi.

摘要

Fungi are ubiquitous eukaryotes that are notorious for causing various problems, but can also be exploited for beneficial purposes. Fungi are responsible for contamination and damage to important crops, and fungal infections in humans are on the rise owing to an increasing population of vulnerable groups and the emergence of medication-resistant fungal pathogens. However, many fungi also produce compounds that have very useful properties, such as the penicillins and the cholesterol-lowering statins.; Research aimed at discovery of improved antifungal agents from natural sources is being pursued in both industry and academia. The most common approaches rely on mass random screening of organisms against an array of specially designed assays. However, this thesis is based on an alternate approach involving selection of fungi for screening on the basis of ecological considerations.; Mycoparasitic and fungicolous fungi colonize other fungal species. As part of the process by which these colonists achieve dominance over the host, these fungi often appear to produce secondary metabolites that are employed to weaken (or kill) the host prior to nutrient absorption. Such metabolites could be useful in the development of new antifungal agents.; Eleven species of mycoparasitic and fungicolous fungi were chosen for chemical investigation on the basis of bioactivities exhibited by extracts from cultures of these species. Chemical studies of these extracts afforded thirteen new metabolites, together with seventeen known compounds. These natural products comprise a diverse group of structures with origins representing polyketide, terpenoid, and shikimate biosynthetic pathways. Most of the new metabolites possess structural features that are uncommon or unprecedented in nature. Some of these compounds displayed potent activity against fungi and/or bacteria.; Selected representatives of another underexplored niche group of fungi that inhabit freshwater environments were also investigated. Fermentation cultures of four such fungal isolates afforded eight metabolites, five of which are new.; The chemical structures of all of these compounds were established by analysis of NMR and MS data. Chemical methods and/or X-ray crystallographic analysis were employed in some instances. Details of the isolation, structure elucidation, and bioactivities of the new metabolites are presented in this thesis.