Beyond its function in cell biology, fatty acid synthase is a potential target for drugs in the treatment of cancer and metabolic disorders such as obesity, making it particularly interesting for medical research. Fatty acids are essential to metabolism in all living organisms. These fatty acids, which are present in the cell membranes, function as energy storage compounds while also serving as messenger molecules. Individual steps in the synthesis have been studied in isolated bacterial enzymes in the past. However, in higher organisms, fatty acid synthesis is catalysed by large multifunctional proteins: many individual enzymes are brought together to form a "molecular assembly line". Following many years of research, Prof. Ban et al. have determined the structures of two representative classes of fatty acid synthases in higher organisms at atomic detail: fungal and mammalian FAS.
These fatty acid synthases represent two different architectural solutions of giant multi-enzymes that shift the products of one enzyme’s active site to the next. Fungal FAS, one of the most complex eukaryotic multi-enzymes, is a large molecule with a mass of 2.6 MDa. The mammalian FAS carries seven functional domains on a single polypeptide chain of approximately 2,500 amino acids and forms a 540,000 Da assembly.
The structures identified by Prof. Ban and his group provide high-resolution structural information on the three-dimensional arrangement of the five catalytic and two non-enzymatic domains of the protein. It also reveals the topology of its linkers and inserted functional domains. The structural insights into FAS can help to understand the dynamic aspects of substrate shuttling in related cellular machines of many multi-enzymes.
Prof. Nenad Ban, born in Zagreb, Croatia, studied at the University of Zagreb. He completed his PhD with the Department of Biochemistry, University of California, at Riverside, USA. For his postdoctoral scientific work he joined the Department of Molecular Biophysics and Biochemistry at Yale University in 1995 where he achieved pioneering results with the X-ray crystallographic structure of the large ribosomal subunit in the laboratory of Nobel laureate Thomas Steitz. In 2000, he was appointed assistant professor of structural molecular biology at the ETH Zurich, becoming a full professor in 2007. The main goal of his research is to study the structure and function of large cellular assemblies using a combination of crystallographic, electron microscopic and biochemical methods. His research has had a significant impact on the fields of protein synthesis and fatty acid synthesis.
The Board of Trustees of the Heinrich Wieland Prize emphasized the fundamental role of Prof. Ban's work for different fields of research. His work on fatty acid synthase even establishes a direct link to Heinrich Wieland whose student and later son-in-law Feodor Lynen (Nobel Prize 1964) first identified the eukaryotic fatty acid synthases and characterized the biological reactions. "In truly pioneering work Nenad Ban succeeded in generating high-quality crystals from these molecular factories and used them to determine their crystal structure at atomic detail" concluded Prof. Konrad Sandhoff (Bonn), Chairman of the Board. "This great achievement now allows for a precise understanding of how these large, complex biological machines function."
The Heinrich Wieland Prize is named after the German Nobel laureate Prof. Heinrich Otto Wieland (1877 to 1957) and has been awarded every year since 1964. It honours outstanding innovative scientific work in the biochemistry, chemistry, physiology und medical aspects of lipids und other biologically active substances. The prize-winner is chosen by an independent Board of Trustees. The Heinrich Wieland Prize is sponsored by Boehringer Ingelheim. Heinrich Wieland, who was related to the founders of Boehringer Ingelheim, set up the company's scientific research department.
Boehringer Ingelheim is one of the world's 15 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 142 affiliates in 50 countries and more than 41,500 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.
In 2009, Boehringer Ingelheim posted net sales of 12.7 billion euro while spending 21% of net sales in its largest business segment, Prescription Medicines, on research and development.