Studies on the genotype, phenotype, and co-cultures of Aspergillus section Fumigati and the development of new techniques to enhance structure elucidation of fungal metabolites

Fungi are pathogenic to plants, humans, and animals, and secondary metabolites produced by fungi are implicated in these interactions. As part of an interdisciplinary project to identify the chemical and genomic differences between pathogenic and non-pathogenic fungi, this research identified the chemical differences among Aspergillus section Fumigati. During the research, eight fungal strains were grown under three different temperatures, and 13 different media types were evaluated for their chemical diversity. Chemical studies resulted in 30 secondary metabolites and a variety of chemometric comparisons. The characterized secondary metabolites were compared between strains using several different methodologies, including chemometrics, dereplication, and biosynthetic gene clusters. These comparisons shed light on how secondary metabolites affect pathogenicity in Aspergillus section Fumigati. Bioinformatic analysis of the genome of Aspergillus fischeri predicted the presence of 48 biosynthetic gene clusters, yet only 5 classes of secondary metabolites were identified by chemical characterization. Interaction-driven secondary metabolite discovery (i.e., co-culturing) was used to activate silent biosynthetic gene clusters. This methodology was utilized successfully by co-culturing A. fischeri and Xylaria flabelliformis, which produces the FDA-approved antifungal drug griseofulvin; to activate secondary metabolites not observed when the two fungi were grown in monoculture. The co-culture resulted in the characterization of a novel scaffold with cytotoxic activity