Figure 2. Schematic illustration of the UQ biosynthetic pathway in the yeast S. cerevisiae.

The pathway starts with assembly and elongation of the isoprenoid tail catalyzed by the enzyme Coq1p (not shown). Coq2p mediates the condensation of the isoprenoid tail with either one of two basic ring structures, para-hydroxybenzoate (4-HB) or para-aminobenzoate (pABA), producing 3-hexaprenyl-4-hydroxybenzoate (HHB) and 3-hexaprenyl-4-aminobenzoic acid (HAB) respectively. The basic ring moiety then undergoes a series of modifications to produce UQ. Enzymes required for 5 of the 7 modifications are shown in blue. A question mark (?) indicates that the protein catalyzing the reaction has yet to be identified. NH2 from pABA and C4-aminated intermediates are shown in red. NH2-to-OH conversion is thought to takes place prior to demethoxyubiquinone (DMQ6) formation. The intermediates that have been detected in yeast coq mutants are shown in brackets. They include HHB and HAB in “ coq3-9 mutants (Tran and Clarke, 2007, Pierrel et al., 2010, Marbois et al., 2010), 3-hexaprenyl-4-hydroxyphenol (4-HP) and 3-hexaprenyl-4-aminophenol (4-AP) in “ coq6 overexpressing Coq8p and in mutant cells deficient in Yalh1 or Ahr1 (Ozeir et al., 2011), 3-hexaprenyl-4-amino-5-hydroxybenzoic acid (HHAB) in “ coq4 cells overexpressing Coq8p and in the “ coq4-1 point mutant (Xie et al., 2012), Demethyl-DMQ₆ (DDMQ₆) in “ coq5 overexpressing Coq8p (Xie et al., 2012), DMQ₆ in a coq7 point mutant (Padilla et al., 2004, Marbois et al., 2010), yeast cells with partial inactivation of Coq7p (Pierrel et al., 2010) and “ coq7 mutants overexpressing Coq8p (Xie et al., 2012); only minute amounts of 4-amino-DMQ₆ (IDMQ₆) were found in wild type yeast cells and in the coq7-1 point mutant as well as in “ coq6 and “ coq9 cells overexpressing Coq8p (Xie et al., 2012) Asterisks indicate compounds that are the main intermediates detected when either 4-HB or pABA are provided as ring precursors. Coq8p is a putative kinase, believed to have a regulatory role in UQ₆ biosynthesis. Deletion of COQ8 affects the phosphorylation states of Coq3p, Coq5p and Coq7p (Xie et al., 2011, Tauche et al., 2008). In addition, Coq4p and Coq9p (not shown) are also required for UQ₆ biosynthesis, although their precise roles remain to be elucidated (Tran and Clarke, 2007).