Synthetic biology tools for transcriptional activation and regulation of biosynthetic gene clusters in filamentous fungi

The increasing number of sequenced fungal genomes revealed a vast of natural product biosynthetic gene clusters (BGCs) with unknown produced compounds. However, most of the fungal SM BGCs are transcriptionally silent under laboratory growth conditions, and the signal or stimulus triggering the transcriptional activation of these clusters is often unknown, rendering these BGC “cryptic”. Obviously, considering the enormous diversity of the fungal kingdom and the notion that BGCs are widespread, characterized SMs so far represent only the tip of the ice-berg. With the advent of synthetic biology novel applications and tools have been developed for fungi, aiming at the transcriptional activation of cryptic BGCs. The objective of this thesis was to develop novel synthetic biology tools for filamentous fungi, with the aim of transcriptional activation of transcriptionally silent and “cryptic” BGCs, as well as the controlled production of BGC encoded secondary metabolites in the fungal host.