Abstract

Fungi are extremely proficient producers of often complex secondary metabolites. The biosynthesis of these compounds is genetically encoded, usually by groups of clustered genes. Many fungi possess up to 100 biosynthetic gene clusters (BGC), each with the potential to produce one or more compounds, but most clusters are either silent (known product, but not produced) or cryptic (unknown product) or both. Numerous methods have been reported for the 'activation' of such BGCs, but none is systematic or widely applicable except for heterologous expression. Rapid cloning methods in yeast, combined with a modular vector series and the tractable host Aspergillus oryzae now enable fast and reliable analysis of fungal BGCs from diverse sources, as well as the investigation of silent and cryptic clusters and the rational engineering of fungal secondary metabolites.