| Abstrakt: |
Pantothenic acid and β-alanine are metabolic intermediates in coenzyme A biosynthesis. Using a functional screen in the yeast Saccharomyces cerevisiae, a putative amine oxidase, encoded by FMS1, was found to be rate-limiting for β-alanine and pantothenic acid biosynthesis. Overexpression ofFMS1caused excess pantothenic acid to be excreted into the medium, whereas deletion mutants required β-alanine or pantothenic acid for growth. Furthermore, yeast genes ECM31andYIL145c, which both have structural homology to genes of the bacterial pantothenic acid pathway, were also required for pantothenic acid biosynthesis. The homology of FMS1to FAD-containing amine oxidases and its role in β-alanine biosynthesis suggested that its substrates are polyamines. Indeed, we found that all the enzymes of the polyamine pathway in yeast are necessary for β-alanine biosynthesis; spe1Δ , spe2Δ ,spe3Δ , and spe4Δ are all β-alanine auxotrophs. Thus, contrary to previous reports, yeast is naturally capable of pantothenic acid biosynthesis, and the β-alanine is derived from methionine via a pathway involving spermine. These findings should facilitate the identification of further enzymes and biochemical pathways involved in polyamine degradation and pantothenic acid biosynthesis in S. cerevisiaeand raise questions about these pathways in other organisms. |
