Black yeasts are efficient heterologous hosts for the production of a wide range of fungal polyketides

Fungal polyketides are a rich source of bioactive molecules. Their biosynthesis is often activated by environmental conditions that are hard to reproduce under laboratory conditions. Heterologous expression bypasses native regulation, enabling systematic polyketide discovery. The most widely used fungal hosts are the highly tractable Saccharomycotina yeasts with a narrow product scope and the metabolically robust but less tractable filamentous Eurotiomycetes. Here we established yeasts of the genera Exophiala and Knufia as hosts for polyketide production. These hosts are genetically tractable and robust, allowing us to heterologously produce six fungal polyketides with different domain architectures: 6-methylsalicylic acid, YWA1, monocillin II, farinosone B and monacolin J. Our findings demonstrate that these yeast hosts can efficiently produce complex polyketides allowing systematic polyketide synthase expression.