Physarum polycephalum expresses a dihydropteridine reductase with selectivity for pterin substrates with a 6-(1', 2'-dihydroxypropyl) substitution.
Physarum polycephalum is one of few non-animal organisms capable of synthesizing tetrahydrobiopterin from GTP. Here we demonstrate developmentally regulated expression of quinoid dihydropteridine reductase (EC 1.6.99.7), an enzyme required for recycling 6,7-[8H]-dihydrobiopterin. Physarum also expresses phenylalanine-4-hydroxylase activity, an enzyme that depends on dihydropteridine reductase. The 24.4 kDa Physarum dihydropteridine reductase shares 43% amino acid identity with the human protein. A number of residues important for function of the mammalian enzyme are also conserved in the Physarum sequence. In comparison to sheep liver dihydropteridine reductase, purified recombinant Physarum dihydropteridine reductase prefers pterin substrates with a 6-(1', 2'-dihydroxypropyl) group. Our results demonstrate that Physarum synthesizes, utilizes and metabolizes tetrahydrobiopterin in a way hitherto thought to be restricted to the animal kingdom.
Wild
Claudia
C
Institute of Medical Chemistry and Biochemistry, University of Innsbruck, Fritz-Pregl-Str. 3, A-6020 Innsbruck, Austria.
Golderer
Georg
G
Gröbner
Peter
P
Werner-Felmayer
Gabriele
G
Werner
Ernst R
ER
D000595:Amino Acid Sequence; D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D004093:Dihydropteridine Reductase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D008969:Molecular Sequence Data; D010651:Phenylalanine Hydroxylase / Q000096:biosynthesis / Q000378:metabolism; D010802:Phylogeny; D016839:Physarum polycephalum / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D011622:Pterins / Q000737:chemistry / Q000378:metabolism*; D011995:Recombination, Genetic; D016415:Sequence Alignment; D013379:Substrate Specificity
D011622:Pterins; D001708:Biopterins; D010651:Phenylalanine Hydroxylase; D004093:Dihydropteridine Reductase; C003402:sapropterin