Resveratrol and para-coumarate serve as ring precursors for coenzyme Q biosynthesis

Abstract

Coenzyme Q (Q or ubiquinone) is a redox-active polyisoprenylated benzoquinone lipid essential for electron and proton transport in the mitochondrial respiratory chain. The aromatic ring 4-hydroxybenzoic acid (4HB) is commonly depicted as the sole aromatic ring precursor in Q biosynthesis despite the recent finding that para-aminobenzoic acid (pABA) also serves as a ring precursor in Saccharomyces cerevisiae Q biosynthesis. In this study, we employed aromatic 13 C 6 -ring-labeled compounds including 13 C 6 -4HB, 13 C 6 -pABA, 13 C 6 -resveratrol, and 13 C 6 -coumarate to investigate the role of these small molecules as aromatic ring precursors in Q biosynthesis in Escherichia coli, S. cerevisiae, and human and mouse cells. In contrast to S. cerevisiae, neither E. coli nor the mammalian cells tested were able to form 13 C 6 -Q when cultured in the presence of 13 C 6 -pABA. However, E. coli cells treated with 13 C 6 -pABA generated 13 C 6 -ring-labeled forms of 3-octaprenyl-4-aminobenzoic acid, 2-octaprenyl-aniline, and 3-octaprenyl-2-aminophenol, suggesting UbiA, UbiD, UbiX, and UbiI are capable of using pABA or pABA-derived intermediates as substrates. E. coli, S. cerevisiae, and human and mouse cells cultured in the presence of 13 C 6 -resveratrol or 13 C 6 -coumarate were able to synthesize 13 C 6 -Q. Future evaluation of the physiological and pharmacological responses to dietary polyphenols should consider their metabolism to Q.