DISCOVERY OF A NEW TETRAHYDROBIOPTERIN-SYNTHESIZING ENZYME IN THE LEMON MUTANT OF THE SILKWORM BOMBYX-MORI

A new tetrahydrobiopterin-synthesizing enzyme, which is different from sepiapterin reductase (EC 1.1.1.153), was discovered in the integumen t of the lemon mutant of the silkworm Bombyx mori. This enzyme convert ed 6-pyruvoyltetrahydropterin to tetrahydrobiopterin, an essential cof actor in the hydroxylation of aromatic amino acids, in the presence of NADPH. The reaction proceeded via 6-lactoyltetrahydropterin and 1'-hy droxy-2'-oxopropyltetrahydropterin as intermediates. The molecular mas s of this enzyme was estimated to be 40 kDa. N-Acetylserotonin, a pote nt inhibitor of sepiapterin reductase, slightly inhibited the enzymati c reaction. In the presence of 0.5 mM N-acetylserotonin, the formation of tetrahydrobiopterin by sepiapterin reductase purified from the nor mal strain silkworm was completely inhibited. However, the formation o f tetrahydrobiopterin by the enzyme purified from the lemon mutant was inhibited by only about 50%. These results suggest an alternative bio synthetic pathway to tetrahydrobiopterin.