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Structure and function of eukaryotic fatty acid synthases

Published online by Cambridge University Press:  24 August 2010

Timm Maier ,
Marc Leibundgut ,
Daniel Boehringer  and
Nenad Ban
Timm Maier
Affiliation:
Institute of Molecular Biology and Biophysics, ETH Zurich, 8093 Zurich, Switzerland
Marc Leibundgut
Affiliation:
Institute of Molecular Biology and Biophysics, ETH Zurich, 8093 Zurich, Switzerland
Daniel Boehringer
Affiliation:
Institute of Molecular Biology and Biophysics, ETH Zurich, 8093 Zurich, Switzerland
Nenad Ban*
Affiliation:
Institute of Molecular Biology and Biophysics, ETH Zurich, 8093 Zurich, Switzerland
*
*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
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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.

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Review Article
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Quarterly Reviews of Biophysics , Volume 43 , Issue 3 , August 2010 , pp. 373 - 422
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Copyright © Cambridge University Press 2010

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