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Microbiology and Molecular Biology Reviews, September 2004, p. 501-517, Vol. 68, No. 3
1092-2172/04/$08.00+0     DOI: 10.1128/MMBR.68.3.501-517.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Microbial Type I Fatty Acid Synthases (FAS): Major Players in a Network of Cellular FAS Systems

Eckhart Schweizer* and Jörg Hofmann

Lehrstuhl für Biochemie der Universität Erlangen-Nürnberg, Erlangen, Germany

The present review focuses on microbial type I fatty acid synthases (FASs), demonstrating their structural and functional diversity. Depending on their origin and biochemical function, multifunctional type I FAS proteins form dimers or hexamers with characteristic organization of their catalytic domains. A single polypeptide may contain one or more sets of the eight FAS component functions. Alternatively, these functions may split up into two different and mutually complementing subunits. Targeted inactivation of the individual yeast FAS acylation sites allowed us to define their roles during the overall catalytic process. In particular, their pronounced negative cooperativity is presumed to coordinate the FAS initiation and chain elongation reactions. Expression of the unlinked genes, FAS1 and FAS2, is in part constitutive and in part subject to repression by the phospholipid precursors inositol and choline. The interplay of the involved regulatory proteins, Rap1, Reb1, Abf1, Ino2/Ino4, Opi1, Sin3 and TFIIB, has been elucidated in considerable detail. Balanced levels of subunits {alpha} and ß are ensured by an autoregulatory effect of FAS1 on FAS2 expression and by posttranslational degradation of excess FAS subunits. The functional specificity of type I FAS multienzymes usually requires the presence of multiple FAS systems within the same cell. De novo synthesis of long-chain fatty acids, mitochondrial fatty acid synthesis, acylation of certain secondary metabolites and coenzymes, fatty acid elongation, and the vast diversity of mycobacterial lipids each result from specific FAS activities. The microcompartmentalization of FAS activities in type I multienzymes may thus allow for both the controlled and concerted action of multiple FAS systems within the same cell.

* Corresponding author. Mailing address: Lehrstuhl für Biochemie der Universität Erlangen-Nürnberg, Staudtstrasse 5, Erlangen 91058, Germany.

Microbiology and Molecular Biology Reviews, September 2004, p. 501-517, Vol. 68, No. 3
1092-2172/04/$08.00+0     DOI: 10.1128/MMBR.68.3.501-517.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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