Team:Wageningen UR

The discovery of secondary metabolites has had a profound influence on the development of human society. It was Alexander Fleming who in 1928 discovered the first antibiotic, penicillin, that would conquer some of mankind's most ancient scourges, including syphilis, gangrene and tuberculosis. The production of these secondary metabolites in most cases involves a large backbone enzyme that contains multiple catalytic domains. One of the goals is to establish a modular system of domain shuffling to generate a plethora of novel enzymes with new and improved functionalities. The possibilities are endless as there is a myriad of different domains from many fungi that can be added, removed, reordered or exchanged in this synthetic biology approach. The production of lovastatin, a drug used in lowering LDL cholesterol for patients suffering from cardiovascular disease, has been chosen as a proof of principle. Currently, it is produced in the fungi Aspergillus terreus, which also produces less desirable toxins. The aim is to transfer the entire lovastatin metabolic pathway from A. terreus into a GRAS organism like Aspergillus niger.