A Saccharomyces cerevisiae gene required for heterologous fatty acid elongase activity encodes a microsomal β-keto-reductase

A number of Saccharomyces cerevisiae membrane-bound oxidoreductases were examined for potential roles in microsomal fatty acid elongation, by assaying heterologous elongating activities in individual deletion mutants. One yeast gene, YBR159w, was identified as being required for activity of both the Caenorhabditis elegans elongase PEA1 (F56H11.4) and the Arabidopsis thaliana elongase FAE1. Ybr159p shows some limited homology to human steroid dehydrogenases and is a member of the short-chain alcohol dehydrogenase superfamily. Disruption of YBR159w is not lethal, in contrast to previous reports, although the mutants are slow growing and display high temperature sensitivity. Both Ybr159p and an Arabidopsis homologue were shown to restore heterologous elongase activities when expressed in ybr159Delta mutants. Biochemical characterization of microsomal preparations from ybr159Delta cells revealed a primary perturbation in beta-ketoacyl reduction, confirming the assignment of YBR159w as encoding a component of the microsomal elongase.