A pathway for degradation of uracil to acetyl coenzyme a in bacillus megaterium

Di Zhu, Yifeng Wei, Jinyu Yin, Dazhi Liu, Ee Lui Ang, Huimin Zhao, Yan Zhang

Research output: Contribution to journalArticlepeer-review


Bacteria utilize diverse biochemical pathways for the degradation of the pyrimidine ring. The function of the pathways studied to date has been the release of nitrogen for assimilation. The most widespread of these pathways is the reductive pyrimidine catabolic pathway, which converts uracil into ammonia, carbon dioxide, and β-alanine. Here, we report the characterization of a β-alanineipyruvate aminotransferase (PydD2) and an NAD+-dependent malonic semialdehyde dehydrogenase (MSDH) from a reductive pyrimidine catabolism gene cluster in Bacillus megaterium. Together, these enzymes convert β-alanine into acetyl coenzyme A (acetyl-CoA), a key intermediate in carbon and energy metabolism. We demonstrate the growth of B. megaterium in defined medium with uracil as its sole carbon and energy source. Homologs of PydD2 and MSDH are found in association with reductive pyrimidine pathway genes in many Gram-positive bacteria in the order Bacillales. Our study provides a basis for further investigations of the utilization of pyrimidines as a carbon and energy source by bacteria.Pyrimidine has wide occurrence in natural environments, where bacteria use it as a nitrogen and carbon source for growth. Detailed biochemical pathways have been investigated with focus mainly on nitrogen assimilation in the past decades. Here, we report the discovery and characterization of two important enzymes, PydD2 and MSDH, which constitute an extension for the reductive pyrimidine catabolic pathway. These two enzymes, prevalent in Bacillales based on our bioinfor- matics studies, allow stepwise conversion of β-alanine, a previous "end product" of the reductive pyrimidine degradation pathway, to acetyl-CoA as carbon and energy source.

Original languageEnglish (US)
Article numbere02837
JournalApplied and environmental microbiology
Issue number7
StatePublished - Apr 1 2020


  • Acetyl-coa
  • Aminotransferase
  • Carbon source
  • Malonic semialdehyde dehydrogenase
  • Pyridoxal phosphate
  • Pyrimidine
  • Pyruvate
  • Reductive pathway
  • Sequence similarity network
  • β-alanine

ASJC Scopus subject areas

  • Biotechnology
  • Food Science
  • Applied Microbiology and Biotechnology
  • Ecology


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