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ThermusQ> Pathway> PWEB0001

Description

The pyrimidine nucleotide biosynthetic pathway was revealed by experiments with a mutant strain of Neurospora crassa. The six-reaction pathway involved in UMP synthesis was revealed when a pyrimidine-requiring strain was given orotate instead of uracil and cytosine, leading to normal growth. Subsequently, the pathway for synthesis of CTP from UMP via UTP was elucidated. In the de novo synthetic pathway of purine nucleotides, the purine base is synthesized using PRPP (phosphoribosyl diphosphate) as the foundation, whereas in the de novo synthetic pathway of pyrimidine nucleotides, the pyrimidine base is first completed and then the ribose-5-phosphate of PRPP is attached. This pathway is essentially common to most organisms, even in Thermus thermophilus.The fourth reaction to produce orotic acid from dihydroorotate uses fumaric acid or NAD+ or quinone as the electron acceptor; Thermus thermophilus is thought to use quinone, but the type of quinone has not been identified. Furthermore, although there are two types of enzymes involved in the seventh reaction that converts UMP to UDP: one that uses both CMP and UMP as substrates, and one that uses only UMP as a substrate, Thermus thermophilus has a UMP-specific type of enzyme.


References

  • Michelson AM, Drell W, Mitchell HK, (1951) A New Ribose Nucleoside from Neurospora. Proc Natl Acad Sci, 37, 396–399.
  • Davis RH, (1960) AN ENZYMATIC DIFFERENCE AMONG PYR-3 MUTANTS OF NEUROSPORA CRASSA. Proc Natl Acad Sci, 46, 677–682.
  • Davis RH, Woodward VW, (1962) THE RELATIONSHIP BETWEEN GENE SUPPRESSION AND ASPARTATE TRANSCARBAMYLASE ACTIVITY IN pyr-3 MUTANTS OF NEUROSPORA. Genetics, 47, 1075–1083.
  • Finck D, Suyama Y, Davis RH, (1965) METABOLIC ROLE OF THE PYRIMIDINE-3 LOCUS OF NEUROSPORA. Genetics, 52, 829–834.
  • Davis R, (1965) Carbamyl phosphate synthesis in Neurospora Crassa II. Genetics, metabolic position, and regulation of arginine-specific carbamyl phosphokinase. Biochim Biophys Acta - Gen Subj, 107, 54–68.
  • Caroline DF, (1969) Pyrimidine Synthesis in Neurospora crassa: Gene-Enzyme Relationships. J Bacteriol, 100, 1371–1377.
  • Schultheisz HL, Szymczyna BR, Scott LG, Williamson JR, (2011) Enzymatic de novo pyrimidine nucleotide synthesis. J Am Chem Soc, 133, 297–304.