Beta oxidation of oleic acid in yeast requires a thioesterase but not dienoyl‐CoA isomerase

Abstract

The β-oxidation of unsaturated fatty acids in yeast was studied by measuring and comparing the growth of wild-type S. cerevisiae with the growth of mutants that either have a deleted Δ3,5, Δ2,4-dienoyl-CoA isomerase (dienoyl-CoA isomerase) gene (DCI1) or thioesterase gene (TES1) on oleic or palmitic acid. Growth of wild-type and dci1 strains on oleic acid was indistinguishable, whereas the tes1 mutant grew slower and to a lower density. In contrast, all three strains grew in a similar manner on palmitic acid. 3,5-Tetradecanoic acid was detected in the medium by gas chromatography/mass spectrometry after growth of wild-type cells on oleic acid but not when palmitic acid was the carbon source. When the tes1 mutant was transformed with a plasmid expressing human dienoyl-CoA isomerase, the growth defect on oleic acid was partially corrected. These observations support the conclusion that the product of the DCI1 gene does not function as dienoyl-CoA isomerase in oleate β-oxidation. Hence 3,5-tetradecadienoyl-CoA, an intermediate of oleate β-oxidation, does not seem to be degraded via the reductase-dependent pathway but rather by an alternate pathway that involves a thioesterase, which hydrolyzes 3,5-tetradecadienoyl-CoA to 3,5-tetradecadienoic acid that is excreted into the growth medium. (Supported by NIH Grants GM08168 and RR03060 and Grant 0350364N from the American Heart Association).