U.S. Department of Defense


Date of this Version



Published in Journal of Biological Chemistry (2006) 281(14): pp. 9018–9029


Several 3-keto-synthases have been studied, including the soluble fatty acid synthases, those involved in polyketide synthesis, and the FAE1-like 3-ketoacyl-CoA synthases. All of these condensing enzymes have a common ancestor and an enzymatic mechanism that involves a catalytic triad consisting of Cys, His, and His/Asn. In contrast to the FAE1-like family of enzymes that mediate plant microsomal fatty acid elongation, the condensation step of elongation in animals and in fungi appears to be mediated by the Elop homologs. Curiously these proteins bear no resemblance to the well characterized 3-keto-synthases. There are three ELO genes in yeast that encode the homologous Elo1p, Elo2p, and Elo3p proteins. Elo2p and Elo3p are required for synthesis of the very long-chain fatty acids, and mutants lacking both Elo2p and Elo3p are inviable confirming that the very long-chain fatty acids are essential for cellular functions. In this study we show that heterologous expression of several Arabidopsis FAE1-like genes rescues the lethality of an elo2Δelo3Δ yeast mutant. We further demonstrate that FAE1 acts in conjunction with the 3-keto and trans-2,3-enoyl reductases of the elongase system. These studies indicate that even though the plantspecific FAE1 family of condensing enzymes evolved independently of the Elop family of condensing enzymes, they utilize the same reductases and presumably dehydratase that the Elop proteins rely upon.