Bioactive Compounds from Extremophilic Marine Fungi

Abstract

The marine world is the largest underexplored ecosystem for bioactive compounds due to its inaccessibility beyond the intertidal, hindering the isolation of new chemical entities. There is reason to explore marine environments, as seven marine natural products have been approved by either the FDA or the EMA, five of which are derived from mutualistic interactions between microorganisms and marine invertebrates. Based on the success of these compounds in the clinic and their production by associated microbes, several research programs focus on natural product isolation from microbes dwelling in marine environments, which for the purpose of this chapter, we define as being extreme environments with high salinity, extreme temperatures, minimal light, as well as variable acidity and pressure. While bacteria, archaea, protists, and unicellular fungi account for the majority of oceanic biomass, fewer natural products have been reported from marine fungi than bacteria. However, with improved sampling, culturing, and molecular-based techniques, the number of bioactive metabolites reported from marine fungi has increased significantly over the last 30 years. Notably, cephalosporins and plinabulin are bioactive compounds inspired by marine fungal natural products and have either been clinically approved or are currently in phase III clinical trials. Herein, we discuss fungal isolates that have produced bioactive compounds, especially those in (pre)clinical trials. While we are finding that marine fungi are prolific sources of novel chemical diversity, we continue to isolate the same species belonging to the Aspergillus, Penicillium, Fusarium, and Cladosporium genera. Thus, potential strategies for improving the search for bioactive compounds from marine fungi will also be mentioned.