Drosophila tan Encodes a Novel Hydrolase Required in Pigmentation and Vision

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Abstract
Many proteins are used repeatedly in development, but usually the function of the protein is similar in the different contexts. Here we report that the classical Drosophila melanogaster locus tan encodes a novel enzyme required for two very different cellular functions: hydrolysis of N-β-alanyl dopamine (NBAD) to dopamine during cuticular melanization, and hydrolysis of carcinine to histamine in the metabolism of photoreceptor neurotransmitter. We characterized two tan-like P-element insertions that failed to complement classical tan mutations. Both are inserted in the 5′ untranslated region of the previously uncharacterized gene CG12120, a putative homolog of fungal isopenicillin-N N-acyltransferase (EC 2.3.1.164). Both P insertions showed abnormally low transcription of the CG12120 mRNA. Ectopic CG12120 expression rescued tan mutant pigmentation phenotypes and caused the production of striking black melanin patterns. Electroretinogram and head histamine assays indicated that CG12120 is required for hydrolysis of carcinine to histamine, which is required for histaminergic neurotransmission. Recombinant CG12120 protein efficiently hydrolyzed both NBAD to dopamine and carcinine to histamine. We conclude that D. melanogaster CG12120 corresponds to tan. This is, to our knowledge, the first molecular genetic characterization of NBAD hydrolase and carcinine hydrolase activity in any organism and is central to the understanding of pigmentation and photoreceptor function. True et al. describe the identification and characterization of the Drosophila melanogaster enzyme Tan. The gene encoding Tan was originally discovered in the early 20th century as a mutant strain lacking the dark pigmentation of wild-type flies, hence the name tan. Flies lacking Tan function also exhibited mysterious abnormalities in vision, for example, in responses to light. The new findings by True et al. help to explain the vastly different functions of Tan in pigmentation and vision. In the developing epidermal cells that secrete the adult cuticle, the enzyme encoded by tan is required for the production of dopamine, which is needed for dark melanin pigmentation. In the eye, the Tan enzyme converts carcinine, a modified form of the neurotransmitter histamine, back to histamine, which is necessary for the rapid and constant neurotransmission events involved in vision. These two enzyme activities have not been previously characterized in any organism. Surprisingly, Tan appears to be closely related to an enzyme in fungi that is used for production of the antibiotic penicillin.