Structural basis for carotenoid cleavage by an archaeal carotenoid dioxygenase

Abstract

Significance The formation of apocarotenoids by carotenoid cleavage dioxygenases (CCDs) is a critical process for several biological signaling systems. However, the active site determinants directing CCDs to cleave a specific alkene bond within the polyene backbone of carotenoids have remained unclear. Through analysis of the previously uncharacterized group of archaeal CCDs, we identified an enzyme, closely related to animal CCDs, that could be isolated in complex with its apocarotenoid product. Its crystal structure revealed the precise molecular interactions governing the enzyme’s unique regioselectivity. These insights pave the way toward control of CCD activity in carotenoid/retinoid metabolism through rational design of small-molecule modulators or targeted mutagenesis.