Catalytic activity and expression of two flavin-containing monooxygenases from Drosophila melanogaster

Two flavin-containing monooxygenase genes occur in the Drosophila genome (named DmFMO-1 and DmFMO-2). Differences exist between these two FMOs in: (1) genomic DNA architecture and predicted post-translational modifications; (2) recombinant protein solubility, activity, and absorbance spectra; and (3) subcellular distribution and developmental transcription/translation profiles in wildtype flies. Characteristic FAD absorbance spectra and strong catalytic competence in methimazole sulfoxidation were observed for recombinant DmFMO-2. Alternatively, weak sulfoxidation was observed for DmFMO-1, which correlated with reduced solubility in the recombinant system. Western blot analyses using specific antisera raised to each FMO showed the two FMOs to be immunologically distinct. In addition, Western blot analyses revealed FMO protein expression in both the microsomal and cytosolic sub-cellular fractions. Interestingly, a larger form of DmFMO-1 occurs in the cytosol that is most strongly expressed in the adult head. These findings suggest divergent physiological roles for DmFMO-1 and DmFMO-2. More specifically, it appears that DmFMO-1 has a distinct developmental role, while DmFMO-2 may have a general housekeeping function.