Identification and characterization of a mammalian enzyme catalyzing the asymmetric oxidative cleavage of provitamin A

In vertebrates, symmetric versus asymmetric cleavage of beta -carotene in t he biosynthesis of vitamin A and its derivatives has been controversially d iscussed. Recently me have been able to identify a cDNA encoding a metazoan beta,beta -carotene-15,15'-dioxygenase from the fruit fly Drosophila melan ogaster, This enzyme catalyzes the key step in vitamin A biosynthesis, symm etrically cleaving beta -carotene to give two molecules of retinal, Mutatio ns in the corresponding gene are known to lead to a blind, vitamin A-defici ent phenotype, Orthologs of this enzyme have very recently been found also in vertebrates and molecularly characterized. Here we report the identifica tion of a cDNA from mouse encoding a second type of carotene dioxygenase ca talyzing exclusively the asymmetric oxidative cleavage of beta -carotene at the 9',10' double bond of beta -carotene and resulting in the formation of beta -apo-10'-carotenal and beta -ionone, a substance known as a floral sc ent from roses, for example. Besides beta -carotene, lycopene is also oxida tively cleaved by the enzyme. The deduced amino acid sequence shares signif icant sequence identity with the beta,beta -carotene-15,15' dioxygenases, a nd the two enzyme types have several conserved motifs, To establish its occ urrence in different vertebrates, we then attempted and succeeded in clonin g cDNAs encoding this new type of carotene dioxygenase from human and zebra fish as web, As regards their possible role, the apocarotenals formed by th is enzyme may be the precursors for the biosynthesis of retinoic acid or ex ert unknown physiological effects. Thus, in contrast to Drosophila, in vert ebrates both symmetric and asymmetric cleavage pathways exist for carotenes , revealing a greater complexity of carotene metabolism.