NC State University
Cytochrome P450 reductase (CPR) is a membrane anchored enzyme in the endo- plasmic reticulum (ER) which shuttles electrons from NADPH to cytochrome P450 (CYP) enzymes via FAD and FMN co-factors. CPRs constitute a small pro- tein family that include one to four members (e.g., one in humans and mammals and three in Sorghum bicolor ). They partner with a large number of CYP pro- teins involved in the biosynthesis of key plant metabolites, such as CYP71AV1 involved in artemisinin biosynthesis within Artemisia annua. To date, although the functions of yeast, human, and mammal CPRs have been comprehensively characterised, their functions among plant homologues remain more understud- ied. The findings presented here are integrated with published data to provide an updated overview of the plant CPR gene family, focusing on their evolution, pref- erences in plant primary and secondary metabolism, the functional contributions of their various domains, and the influence of the connecting domain and hinge on conformational dynamics. Although CPR1 and CPR2 have been reported to involve plant primary and secondary metabolism, the phylogenetic analyses pre- sented here suggest that the current classification of some CPR members requires re-evaluation to better resolve their evolutionary relationships and functional divergence. The length and amino acid composition of the hinge and its contribu- tions to conformational flexibility are also discussed. Available evidence indicates that the structural properties of the CPR hinge is a critical determinant of CPR conformational ability, thus influencing the efficiency of electron transfer to CYP enzymes. In summary, this updated synthesis provides new insights into the evo- lution, structure, and functional diversification of plant CPRs and establishes a framework for elucidating their roles in plant metabolism.