Ecology and taxonomy driven discovery of new bioactive natural products

Fungal exometabolites (natural products) are common among the large fungal genera Aspergillus, Penicillium and Talaromyces. According to a recent revision, these genera contain 344, 349 and 89 species, respectively and all species produce a large number of exometabolites that can be ordered into biosynthetic families. A screening of isolates from all these species have shown that Penicillium and Aspergillus have many exometabolites in common, while Talaromyces produce quite different, often unique exometabolites. The isolates in a fungal species produce similar profiles of exometabolites, and sequencing of genomes has shown that many more exometabolites than the known could be expressed under the right conditions. Different methods have been shown to allow expression of these exometabolites, but ecological knowledge has been shown to help trigger what was formerly regarded as unexpressed exometabolites. For example whole raisins in the growth medium triggered sclerotium formation in Aspergillus niger, and 13 indoloterpenes could be detected from these sclerotia.  Analytical methods for exometabolites have improved considerably, but effective separation from the medium constituents and from other fungal exometabolites and identification via spectrometric methods are important to secure correct qualification and quantification. The analytical chemical methods used are often UHPLC coupled with diode array detection (DAD) or high resolution mass spectrometric (HR-MS-MS) detection.  Examples will be given on how to identify important fungi and their exometabolite profiles, with an emphasis on Penicillium, Aspergillus and Talaromyces and an overview of all exometabolites in those important genera will be given with hints also on misidentified fungi and metabolites.