Eukaryotic beta-alanine synthases are functionally related but have a high degree of structural diversity.
beta-Alanine synthase (EC 3.5.1.6), which catalyzes the final step of pyrimidine catabolism, has only been characterized in mammals. A Saccharomyces kluyveri pyd3 mutant that is unable to grow on N-carbamyl-beta-alanine as the sole nitrogen source and exhibits diminished beta-alanine synthase activity was used to clone analogous genes from different eukaryotes. Putative PYD3 sequences from the yeast S. kluyveri, the slime mold Dictyostelium discoideum, and the fruit fly Drosophila melanogaster complemented the pyd3 defect. When the S. kluyveri PYD3 gene was expressed in S. cerevisiae, which has no pyrimidine catabolic pathway, it enabled growth on N-carbamyl-beta-alanine as the sole nitrogen source. The D. discoideum and D. melanogaster PYD3 gene products are similar to mammalian beta-alanine synthases. In contrast, the S. kluyveri protein is quite different from these and more similar to bacterial N-carbamyl amidohydrolases. All three beta-alanine synthases are to some degree related to various aspartate transcarbamylases, which catalyze the second step of the de novo pyrimidine biosynthetic pathway. PYD3 expression in yeast seems to be inducible by dihydrouracil and N-carbamyl-beta-alanine, but not by uracil. This work establishes S. kluyveri as a model organism for studying pyrimidine degradation and beta-alanine production in eukaryotes.
Gojković
Z
Z
Section of Molecular Microbiology, BioCentrum DTU, DK-2800 Lyngby, Denmark.
Sandrini
M P
MP
Piskur
J
J
D000581:Amidohydrolases / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D004023:Dictyostelium / Q000201:enzymology; D004331:Drosophila melanogaster / Q000201:enzymology; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D008969:Molecular Sequence Data; D011487:Protein Conformation; D012333:RNA, Messenger / Q000235:genetics; D012440:Saccharomyces / Q000201:enzymology / Q000235:genetics / Q000254:growth & development; D017386:Sequence Homology, Amino Acid
D012333:RNA, Messenger; D000581:Amidohydrolases; C021590:beta-ureidopropionase