Characterization of a cetacean aromatase (CYP19) and the phylogeny and functional conservation of vertebrate aromatase
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abstract
Aromatase (cytochrome P450 19, CYP19, P450arom) is the enzyme responsible for the production of estrogens, hormones critical for development and reproduction. Aromatase was sequenced from a white-sided dolphin (Lagenorhynchus acutus) ovary, transiently transfected into HEK 293 cells, and the expressed protein was characterized for aromatase activity in the presence of androstenedione and testosterone and after exposure to the aromatase inhibitor letrazole. The Kms for androstenedione and testosterone were 63.5 and 75 nM, respectively, values that are very similar to those reported for other mammalian aromatases. A Bayesian phylogenetic analysis of the vertebrate aromatases was performed on the amino acid sequences of aromatases from fish, amphibians, reptiles, birds, and mammals. Based on known species phylogeny, the cetacean aromatase showed an expected grouping with artiodactyls (cow, sheep, and goat). An analysis of functional divergence showed strong conservation of aromatase across the entire protein, which indicates that the observed sequence divergence is functionally neutral.
