A comprehensive reconstruction of the fatty acid biosynthesis in Saccharomyces cerevisiae

The role of lipids in eukaryotic cells is of high importance. They are one of the main components of cell membranes, act as storage of high potential energy as well as being a scaffold of signaling proteins or participate in signaling themselves. Many diseases are associated with alterations in the lipid distribution in the cell and the composition of membrane domains. Metabolic syndrome, obesity, atherosclerosis, as well as Alzheimer’s, Huttington diseases and cancer, all originate from alterations in some stage of lipid biosynthesis. Therefore, advancement of knowledge in the field of lipid metabolism will provide novel insights for further biomedical research and potential strategies for drug development. Fatty acids are the backbone of the lipid metabolism. Being lipids themselves they also participate in the biosynthesis of the majority of the lipid classes. Thus, the study of their synthesis and biotransformation in a cell constitutes the basic step towards a systematic investigation of the phenomena attributed to lipids. In the current study we reconstructed a comprehensive representation of the biosynthesis of fatty acids in a model eukaryote such as Saccharomyces cerevisiae. The model accounts for approximately 300 reactions and 230 metabolites, taking part in 3 compartments of the cell, describing the steps of synthesis, elongation and β-oxidation of fatty acids. We make use of other systems approaches in order to identify the input fluxes to the model and we explore the diverse capabilities of the network with respect to flux profiles and distribution of fatty acids.