The eye color pigments of Drosophila melanogaster are composed of red and brown pigments. The purpled eye color of purple (pr) mutants is the result of a defect in the synthesis of the wild-type pigment, drosopterins (Kim, Yim 1995). Drosopterins are produced non-enzymatically by the condensation of PDA with 7,8-dihydropyran (Brown 1986). The pathway leading to the biosynthesis of drosopterin was proposed by two scientists named Brown and Dorsett. The first step in drosopterin biosynthesis is the formation of H2NTP (dihydroneopterin triphosphate) from GTP.
GTP is converted to Hz-NTP by GTP cyclohydrolase encoded by the Punch gene. Hz-NTP is then converted to 6- pyruvoyl tetrahydrobiopterin (6-PTP) by PTP synthase, the product of the purple gene. Drosopterins are synthesized from two molecules of 6- pyruvoyl tetrahydrobiopterin (Kim 1995). The carbon side chain is then cleaved from PTP. After that, the 7,8-dihydropyran condenses with PDA to produce one molecule of drosopterin. 6-PTP is also the intermediate precursor for the yellow eye pigment, sepiapterin, and the important coenzyme, H4-biopterin.
The purple locus of Drosophila melanogaster has been suggested to be the structural gene for PTP synthase.
Wiederrecht and Brown first identified PDA synthase activity and partially purified the enzyme from Drosophila heads. From an analysis of various eye color mutants, they showed that at least three enzymes are involved in the conversion of H2NTP into PDA: one, called sepiapterin synthase A, present in limited amounts in purple; a second, named PDA synthase, that is missing in sepia, and a third deficient in a clot.
Since the addition of partially purified PDA synthase to heated extracts of sepia increased PDA synthesis to the wild-type level, they suggested that sepia+ encodes the structural gene for PDA synthase (Kim 2006). Due to the lower level of PDA synthase activity in the flies, PDA would be rate-limiting for the condensation reaction. The purple gene product, later purified and characterized as 6-PTP synthase, is required for the Mg2+-dependent conversion of the H2NTP into 6-PTP (Switchenko 1984).
The reduced pteridine pigment levels correlate with reduced levels of pyruvoyl tetrahydrobiopterin synthase in the heads of mutant flies. PTP synthase is a key to the synthesis of an essential enzyme cofactor, biopterin, the amounts of sepiapterin, and red pteridine eye pigments (also known as drosopterins) in Drosophila melanogaster are known to be reduced in the purple compared to wild type flies. After testing eye color mutation, only purple (pr) flies contained PTP activity that was lower than that found in the wild-type flies. Mutants deficient in pteridines, sepiapterin, and the drosopterins are lower in wild type than in pr1 and pr(BW), the effect is even greater in pr(BW) than in pr1. Purple produces two PTP synthases from two different promoters. The small transcript is expressed during the early young adult stages when eye pigment synthesis is high. The large transcript is expressed during the synthesis of tetrahydrobiopterin. These two promoters that are produced in Drosophila melanogaster are similar in size and sequence to the human’s PTP synthase (Kim 1996). The major difference between the Drosophila sequence from the human and rat sequences is that the Drosophila’s amino acids are a little bit longer from the C terminus (Kim 1996).