Many microorganisms produce secondary metabolites that are believed to have critical roles in intra- and inter-species communication, competition for resources, or defense of a symbiotic partner. Despite the importance of these metabolites, it is estimated that only a small fraction of fungal secondary metabolites has been identified, and a much smaller fraction of identified secondary metabolites have well-established ecological functions. Two prominent challenges are that most fungi do not express their secondary metabolites under standard laboratory culture conditions, and that there is no straightforward method for identifyingnovel secondary metabolites from complex extracts. Here we present new fungal chemistry from gene activation experiments using cocultivation and epigenetic manipulation. We employ multi-channel metabolomics to rapidly identify new metabolites, and leverage a panel of assays to assess biological function. We found new, cytotoxic bianthrones called allianthrones A-F by co-culture of two discrete developmental stages of Aspergillus alliaceus. Treatment of Chalara sp. with histone deacetylase inhibitorsresulted in the production of new chalanilines A and B, ‘unnatural’ natural products with cytotoxic and antibacterial properties.
Full conference title:
- Fungal Genetics Conference 30th (2019)