TY  - JOUR
A1  - Marelja, Zvonimir
A1  - Dambowsky, Miriam
A1  - Bolis, Marco
A1  - Georgiou, Marina L.
A1  - Garattini, Enrico
A1  - Missirlis, Fanis
A1  - Leimkühler, Silke
T1  - The four aldehyde oxidases of Drosophila melanogaster have different gene expression patterns and enzyme substrate specificities
JF  - The journal of experimental biology
N2  - In the genome of Drosophila melanogaster, four genes coding for aldehyde oxidases (AOX1-4) were identified on chromosome 3. Phylogenetic analysis showed that the AOX gene cluster evolved via independent duplication events in the vertebrate and invertebrate lineages. The functional role and the substrate specificity of the distinct Drosophila AOX enzymes is unknown. Two loss-of-function mutant alleles in this gene region, low pyridoxal oxidase (Po-lpo) and aldehyde oxidase-1 (Aldox-1(n1)) are associated with a phenotype characterized by undetectable AOX enzymatic activity. However, the genes involved and the corresponding mutations have not yet been identified. In this study we characterized the activities, substrate specificities and expression profiles of the four AOX enzymes in D. melanogaster. We show that the Po-lpo-associated phenotype is the consequence of a structural alteration of the AOX1 gene. We identified an 11-bp deletion in the Po-lpo allele, resulting in a frame-shift event, which removes the molybdenum cofactor domain of the encoded enzyme. Furthermore, we show that AOX2 activity is detectable only during metamorphosis and characterize a Minos-AOX2 insertion in this developmental gene that disrupts its activity. We demonstrate that the Aldox-1(n1) phenotype maps to the AOX3 gene and AOX4 activity is not detectable in our assays.
KW  - Aldehyde oxidase
KW  - Molybdoenzymes
KW  - Drosophila melanogaster
KW  - Gene duplication
KW  - Substrate specificities
Y1  - 2014
U6  - https://doi.org/10.1242/jeb.102129
SN  - 0022-0949
SN  - 1477-9145
VL  - 217
IS  - 12
SP  - 2201
EP  - 2211
PB  - Company of Biologists Limited
CY  - Cambridge
ER  -