Synthesis of Secondary Metabolites in Filamentous Fungi

Fungal secondary metabolites have a long history as antibiotic agents. One prominent example is penicillin. Novel antibiotics are often based on cyclic depsipeptides (CDPs). However, the production of these antibiotics on an industrial scale is known to be problematic. Optimization of the synthesis can be achieved by using fungal expression systems.

The innovation presented here contains a process for the synthesis of secondary metabolites such as cyclodepsipeptides in fungal host organisms (genera: Aspergillus, Penicillum, yeast). The necessary fungal enzymes can be modified by the introduction of altered gene sequences (synthetic or designed by PCR). Expression is performed by an inducible, controllable and metabolism-independent system, such as the tetracycline (Tet) system. This system can be switched on or off by constitutive, inducible or suppressible promoters and thus offers the possibility for further optimization. Following fed-batch cultivation, the extraction of the secondary metabolite from the biomass achieves satisfactory yields with high purity and low background contamination by other metabolites.