Specialization of Function Among Aldehyde Dehydrogenases: The ALD2 and ALD3 Genes Are Required for ß-Alanine Biosynthesis in Saccharomyces cerevisiae

Corresponding author: Jeremy H. Toyn, Bristol-Myers Squibb, Experimental Station, E400/3227, Wilmington, DE 19880., jeremy.toyn{at}bms.com (E-mail)

Communicating editor: A. P. MITCHELL

The amino acid ß-alanine is an intermediate in pantothenic acid (vitamin B₅) and coenzyme A (CoA) biosynthesis. In contrast to bacteria, yeast derive the ß-alanine required for pantothenic acid production via polyamine metabolism, mediated by the four SPE genes and by the FAD-dependent amine oxidase encoded by FMS1. Because amine oxidases generally produce aldehyde derivatives of amine compounds, we propose that an additional aldehyde-dehydrogenase-mediated step is required to make ß-alanine from the precursor aldehyde, 3-aminopropanal. This study presents evidence that the closely related aldehyde dehydrogenase genes ALD2 and ALD3 are required for pantothenic acid biosynthesis via conversion of 3-aminopropanal to ß-alanine in vivo. While deletion of the nuclear gene encoding the unrelated mitochondrial Ald5p resulted in an enhanced requirement for pantothenic acid pathway metabolites, we found no evidence to indicate that the Ald5p functions directly in the conversion of 3-aminopropanal to ß-alanine. Thus, in Saccharomyces cerevisiae, ALD2 and ALD3 are specialized for ß-alanine biosynthesis and are consequently involved in the cellular biosynthesis of coenzyme A.

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