Matthew Toomey published an article in Current Biology on the enzymatic mechanisms behind the production of ketocarotenoid.
Red ketocarotenoid-based coloration is an important signal for many vertebrate species and is often generated by adding C4-keto groups to diet-derived carotenoids, like zeaxanthin and beta-carotene. Yet, the enzymatic mechanisms catalyzing this conversion were not well understood. To search for these mechanisms we examined gene expression in the red cone photoreceptors of the avian retina. These photoreceptors specifically accumulate metabolically-derived red ketocarotenoids and have elevated expression of CYP2J19, an enzyme previously implicated in red color expression, and a short-chain dehydrogenase/reductase enzyme BDH1L. We cloned these candidate genes, tested their enzymatic function in cell culture, and found that expression of both enzymes is required to produce C4-ketocarotenoids from precursor carotenoids (e.g zeaxanthin is converted to astaxanthin). In collaboration with David Parichy at the University of Virginia, we identified homologs of these enzymes in fish (Cyp2ae2 and Bdh1a) and we demonstrated that these enzymes are necessary and sufficient for red color expression in relatives of the zebrafish. Finally, in collaboration with Miguel Carniero at Universidade do Porto, we examined genetic differences between red and yellow morphs of several domesticated songbird species and found that the yellow morph, of a typically red species, was linked to mutations in tetratricopeptide repeat protein 39B (TTC39B) gene. When we expressed the TTC39B protein in combination with CYP2J19 and BDH1L, we found that this it enhanced the production ketocarotenoids through a yet-to-be-determined mechanism. These discoveries open up new avenues for understanding the evolution and function of red coloration in vertebrates.