The filamentous fungus Penicillium chrysogenum is the major producer of the beta-lactam antibiotic penicillin. In addition to the penicillin biosynthesis cluster, the genome of P. chrysogenum contains a large number of uncharacterized secondary metabolite gene clusters. However, many of these clusters are not expressed under laboratory conditions. This thesis summarizes the steps of developing a novel, orthogonal, synthetic transcriptional regulation system in P. chrysogenum. The system utilizes transcriptional regulatory genes to express the gene of interests with a strong but controllable manner. The build system can be used for heterologous expression or silenced genes, even whole gene clusters can be activated with it.