Integrated profiling of furanocoumarins (FCs) in grapefruit and derived hybrids toward selection of

Furanocoumarins (FCs) are a class of organic chemical components in grapefruits and other food plants. Consumption of grapefruit juice can potentially increase the bioavailability of a number of clinically prescribeddrugs, induce grapefruit-drug interactions, and therefore, some physicians recommend that grapefruit juiceshould be avoided by patients taking these drugs. To develop low FC grapefruit cultivars, integrated approachesto profile FCs were used to facilitate achieving the goal, including quantifying different FCs in grapefruit andpummelo, characterizing the inheritance using hybrid populations, identifying some key controlling genes inthe furanocoumarin biosynthesis pathway, and determining the inhibitory potency of different hybrids andFCs. We monitored seven FCs, 6’,7’-dihydroxybergamottin (6,7-DHB), bergamottin, bergaptol, isoimperatorin,epoxybergamottin (EBM), 5’,8’-dimethylallyloxypsoralen (5,8-DMP), and Paradisin C, in randomly selectedhybrids, and found 6,7-DHB, bergamottin, paradisin C, and bergaptol inherited in a 1:1 co-segregating manner,with strong correlations (R2 up to 0.909) among them, as well as with in vitro inhibitory potency versus humancytochrome P450-3A activity (R2=0.96). At least one gene in the pathway was identified to show differentialexpression between high and low FC varieties. The phytochemical, genetic, genomic, and pharmaceuticalprofiles of the FCs are leading to a genomic and breeding solution to the grapefruit FC-drug interaction issue.