Structure and function of eukaryotic fatty a cid synthases

In all organisms, fatty acid synthesis is achieved in variations of a common cyclic reaction pathway by stepwise, iterative elongation of precursors with two-carbon extenderunits. In bacteria, all individual reaction steps are carried out by monofunctional dissociatedenzymes, whereas in eukaryotes the fatty acid synthases (FASs) have evolved into largemultifunctional enzymes that integrate the whole process of fatty acid synthesis. During thelast few years, important advances in understanding the structural and functional organizationof eukaryotic FASs have been made through a combination of biochemical, electronmicroscopic and X-ray crystallographic approaches. They have revealed the strikingly differentarchitectures of the two distinct types of eukaryotic FASs, the fungal and the animal enzymesystem. Fungal FAS is a 2 6 MDa a6b6heterododecamer with a barrel shape enclosing twolarge chambers, each containing three sets of active sites separated by a central wheel-likestructure. It represents a highly specialized micro-compartment strictly optimized for theproduction of saturated fatty acids. In contrast, the animal FAS is a 540 kDa X-shapedhomodimer with two lateral reaction clefts characterized by a modular domain architectureand large extent of conformational flexibility that appears to contribute to catalytic efficiency.