Quarterly Reviews of Biophysics

Review Article

Structure and function of eukaryotic fatty acid synthases

Timm Maiera1, Marc Leibundguta1, Daniel Boehringera1 and Nenad Bana1 c1

a1 Institute of Molecular Biology and Biophysics, ETH Zurich, 8093 Zurich, Switzerland

Abstract

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 extender units. In bacteria, all individual reaction steps are carried out by monofunctional dissociated enzymes, whereas in eukaryotes the fatty acid synthases (FASs) have evolved into large multifunctional enzymes that integrate the whole process of fatty acid synthesis. During the last few years, important advances in understanding the structural and functional organization of eukaryotic FASs have been made through a combination of biochemical, electron microscopic and X-ray crystallographic approaches. They have revealed the strikingly different architectures of the two distinct types of eukaryotic FASs, the fungal and the animal enzyme system. Fungal FAS is a 2·6 MDa α6β6 heterododecamer with a barrel shape enclosing two large chambers, each containing three sets of active sites separated by a central wheel-like structure. It represents a highly specialized micro-compartment strictly optimized for the production of saturated fatty acids. In contrast, the animal FAS is a 540 kDa X-shaped homodimer with two lateral reaction clefts characterized by a modular domain architecture and large extent of conformational flexibility that appears to contribute to catalytic efficiency.

Correspondence:

c1 Author for correspondence: Nenad Ban, Institute of Molecular Biology and Biophysics, ETH Zurich, 8093 Zurich, Switzerland. Tel.: +4144 6332785; Fax: +41 44 6331246; Email: ban@mol.biol.ethz.ch