Secondary metabolites containing a decalin motif present high structural and functional diversity due to the multiple possible substitutions on the decalin scaffold and its pendent chains. Several fungal decalin polyketides present remarkable biological activities (Fig. ). For example, lovastatin is widely used as a cholesterol-lowering agent, while equisetin shows HIV integrase inhibitory activity. Fusarielin A, isolated from various Fusarium species, presents antifungal, antiangiogenic and antiproliferative activities. Other fungal decalins include betaenones A-C, which show phytotoxic activity, and campafungins A-D, which display promising activity against Cryptococcus neoformans. Bioinformatic analysis of our recently published A. burnettii genome sequence has also allowed us to identify the putative biosynthetic gene cluster (BGC) responsible for the biosynthesis of 1 (bue) and to explore synthetic biology approaches for the production of 1, given that A. burnettii only produces modest amounts of 1 amongst a suite of other major cometabolites. Heterologous expression of the bue cluster in Aspergillus nidulans with transcription factor overexpression has provided valuable insights into the biosynthesis of 1 and has provided an alternative source to access 1 and its pathway intermediates for bioactivity studies.