SUMMARY PARAGRAPH for FAA4
In order for yeast to utilize fatty acids, either as an energy source (via beta-oxidation) or for essential processes such as phospholipid biosynthesis and protein myristoylation, the fatty acids must first be converted into activated intermediates, acyl-CoAs, through thioesterification of fatty acids with coenzyme A. When fatty acids are synthesized de novo, activation is part of the process of synthesis and is accomplished by the same fatty acid synthetase complex (Fas1p-Fas2p) that initiates and elongates the fatty acid chain. However, yeast cells can also utilize exogenous, imported fatty acids, an ability that becomes essential if the fatty acid synthetase complex is inactivated by mutation or specific inhibitors such as cerulenin. These exogenous fatty acids are activated by one of five characterized yeast acyl-CoA synthetases: Faa1p, Faa2p, Faa3p, Faa4p, or Fat1p (see 8 and 9 for review).
FAA1 and FAA4 encode acyl-CoA synthetases with similar specificities and biological roles (10, 1). Both enzymes can activate fatty acids of a wide range of sizes, but have preferences for long chain lengths (C12:0-C16:0) (11, 12). Faa1p accounts for the majority of the detectable acyl-CoA synthetase activity during exponential growth (10) and FAA1 is expressed at much higher levels than all other FAA genes, under all conditions tested (3). Nevertheless, although faa1 deletion mutants have slight growth abnormalities, these cells still clearly import, activate and beta-oxidize exogenous fatty acids (10). faa1faa4 double mutant cells, however, are inviable in media containing cerulenin, and this phenotype can be completely rescued by overexpression of either FAA1 or FAA4, but not of FAA2 or FAA3 (1).
faa1faa4 double deletion mutants also have severe defects in the import of long chain fatty acids, indicating that these genes play some role in transport as well (13, 4). Overexpression of FAT1 can rescue the faa1faa4 import phenotype and there is evidence of physical interaction between Fat1p and Faa1p and/or Faa4p (4). Fat1p, Faa1p and Faa4p are hypothesized to couple import and activation of exogenous fatty acids by a process called vectorial acylation, wherein fatty acids are metabolically trapped as CoA thioesters upon transport (reviewed in 9). This process is thought to require Fat1p along with either Faa1p and/or Faa4p (4).
FAA4, unlike FAA1, is specifically induced during the diauxic/early post-diauxic transition and may be particularly important under starvation conditions. Higher levels of Faa4p help produce the activated fatty acids necessary for creating N-myristoylproteins, which are thought to play crucial roles in cell survival during stationary phase (3).
Last updated: 2010-02-11