An extended bacterial reductive pyrimidine degradation pathway that enables nitrogen release from β-alanine.

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  • Additional Information
    • Source:
      Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1083-351X (Electronic) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE
    • Publication Information:
      Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology
      Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology
    • Subject Terms:
      Metabolic Networks and Pathways*/drug effects; Bacillaceae/*metabolism ; Nitrogen/*metabolism ; Pyrimidines/*metabolism ; beta-Alanine/*metabolism; Bacillaceae/drug effects ; Bacillaceae/growth & development ; Bacterial Proteins/metabolism ; Biocatalysis/drug effects ; Kinetics ; Multigene Family ; Nitrogen/pharmacology ; Recombinant Proteins/biosynthesis ; Uracil/metabolism
    • Abstract:
      The reductive pyrimidine catabolic pathway is the most widespread pathway for pyrimidine degradation in bacteria, enabling assimilation of nitrogen for growth. This pathway, which has been studied in several bacteria including Escherichia coli B, releases only one utilizable nitrogen atom from each molecule of uracil, whereas the other nitrogen atom remains trapped in the end product β-alanine. Here, we report the biochemical characterization of a β-alanine:2-oxoglutarate aminotransferase (PydD) and an NAD(P)H-dependent malonic semialdehyde reductase (PydE) from a pyrimidine degradation gene cluster in the bacterium Lysinibacillus massiliensis Together, these two enzymes converted β-alanine into 3-hydroxypropionate (3-HP) and generated glutamate, thereby making the second nitrogen from the pyrimidine ring available for assimilation. Using bioinformatics analyses, we found that PydDE homologs are associated with reductive pyrimidine pathway genes in many Gram-positive bacteria in the classes Bacilli and Clostridia. We demonstrate that Bacillus smithii grows in a defined medium with uracil or uridine as its sole nitrogen source and detected the accumulation of 3-HP as a waste product. Our findings extend the reductive pyrimidine catabolic pathway and expand the diversity of enzymes involved in bacterial pyrimidine degradation.
      (© 2019 Yin et al.)
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    • Contributed Indexing:
      Keywords: 2-oxoglutarate; 3-hydroxypropionate; aminotransferase; beta-alanine; enzyme kinetics; enzyme phylogeny; malonic semialdehyde reductase; nitrogen assimilation; nitrogen metabolism; pyridoxal phosphate; pyrimidine; reductase; reductive pathway
    • Accession Number:
      0 (Bacterial Proteins)
      0 (Pyrimidines)
      0 (Recombinant Proteins)
      11P2JDE17B (beta-Alanine)
      56HH86ZVCT (Uracil)
      K8CXK5Q32L (pyrimidine)
      N762921K75 (Nitrogen)
    • Subject Terms:
      Lysinibacillus massiliensis
    • Publication Date:
      Date Created: 20190829 Date Completed: 20200602 Latest Revision: 20210205
    • Publication Date:
      20231215
    • Accession Number:
      PMC6816092
    • Accession Number:
      10.1074/jbc.RA119.010406
    • Accession Number:
      31455636