Molecular Biotechnology of Natural Products
In this research area we have been working on (1) the identification of novel natural products by applying molecular genetic techniques (genome mining, activation of silent gene clusters, expression of gene clusters in a heterologous host) and (2) the identification of novel, potent antifungal compounds. (3) Moreover, we are investigating signal transduction pathways, which give hints on the biological activity of compounds.
Filamentous fungi have the ability to produce a myriad of natural products that are both biologically and pharmacologically active. However, many of the gene clusters involved in their biosynthesis are silent under standard laboratory conditions. We employ different strategies to activate silent gene clusters including genetic tools (overexpression of transcription factors) and epigenetic tools (alteration of chromatin modification). Additionally, we use Saccharomyces cerevisiae as a means of assembling DNA fragments by in vivo recombination, in order to express polycistronic mRNAs containing entire biosynthesis gene clusters from a single promoter in amenable hosts.
Environmental changes are sensed by fungi and transduced via signal transduction pathways. Comparative studies highlighted that MAPKs, calmodulin/calcineurin, TOR and Ras/cAMP signalling pathways are well conserved in eukaryotic organisms. Furthermore, bioinformatic analyses have given a good overview about signalling pathways present in different fungi. We analyse these pathways by applying a combination of systems biological and experimental approaches. These approaches enable us to elucidate the meaning of signal transduction pathways for gene regulation, biosynthesis processes (white biotechnology) and virulence determinants (infection biology) in filamentous fungi.