Lay summary

As the universal main component of cell membranes, lipids form the barrier between the inside of a cell and its surroundings. They are the most important energy storage compounds in our body and act as messengers and transmitters. The abnormal regulation of lipid metabolism plays an important role in the development if cancer and is a very common risk factor for cardiovascular disease and type 2 diabetes.

This project focuses on multifunctional protein complexes as key players in the biosynthesis of lipids and their constituent fatty acids and in metabolic regulation. The goal is to determine the complex structures of enzymes involved in lipid and fatty acid metabolism down to the atomic level. From these structures and further experiments we deduce the mechanism of action of multifunctional proteins and establish opportunities for manipulating them. An example of such proteins is fatty acid synthase, a complex multienzyme in fatty acid biosynthesis and a metabolic oncogene and prognostic maker for tumor malignancy. As a key method for structure determination of large biomacromolecular complexes we employ X-ray crystallography. Our structural and functional data help to gain an understanding of the complex multifunctional proteins typical for human metabolism and deliver starting points for the design or optimization of metabolism-based drugs.