Saccharomyces cerevisiae is capable of de novo pantothenic acid biosynthesis involving a novel pathway of beta-alanine production from spermine

Pantothenic acid and beta -alanine are metabolic intermediates in coenzyme A biosynthesis, Using a functional screen in the yeast Saccharomyces cerevi siae, a putative amine oxidase, encoded by FMS1, was found to be rate-limit ing for beta -alanine and pantothenic acid biosynthesis. Overexpression of FMS1 caused excess pantothenic acid to be excreted into the medium, whereas deletion mutants required beta -alanine or pantothenic acid for growth. Fu rthermore, yeast genes ECM31 and YIL145c, which both have structural homolo gy to genes of the bacterial pantothenic acid pathway, were also required f or pantothenic acid biosynthesis. The homology of FMS1 to FAD-containing am ine oxidases and its role in beta -alanine biosynthesis suggested that its substrates are polyamines. Indeed, we found that all the enzymes of the pol yamine pathway in yeast are necessary for beta -alanine biosynthesis; spe1 Delta, spe2 Delta, spe3 Delta, and spe4 Delta are all beta -alanine auxotro phs, Thus, contrary to previous reports, yeast is naturally capable of pant othenic acid biosynthesis, and the beta -alanine is derived from methionine via a pathway involving spermine. These findings should facilitate the ide ntification of further enzymes and biochemical pathways involved in polyami ne degradation and pantothenic acid biosynthesis in S. cerevisiae and raise questions about these pathways in other organisms.