CLONING OF A RAT CDNA-ENCODING DIHYDROXYPOLYPRENYLBENZOATE METHYLTRANSFERASE BY FUNCTIONAL COMPLEMENTATION OF A SACCHAROMYCES-CEREVISIAE MUTANT DEFICIENT IN UBIQUINONE BIOSYNTHESIS

3,4-Dihydroxy-5-hexaprenylbenzoate methyltransferase (DHHB-MTase) is t he product of the COQ3 gene in Saccharomyces cerevisiae and catalyses the fourth step in the biosynthesis of ubiquinone (coenzyme Q) from p- hydroxybenzoic acid. A full-length cDNA encoding a mammalian homologue of DHHB-MTase was isolated from a newly constructed rat testis cDNA l ibrary by functional complementation of a coq3 deletion mutant of S. c erevisiae. The complementing clone contained a 1.1-kb poly(A)(+)-taile d insert with a 858-bp open reading frame and presumably encodes 3,4-d ihydroxy-5-polyprenylbenzoate-MTase. The deduced rat amino acid (aa) s equence has a 39% identity over 138 aa with the yeast DHHB-MTase and a 37% identity over this same region with an Escherichia coli protein e ncoded by the ubiG gene, a MTase that catalyses the terminal step of u biquinone biosynthesis. The rescue of the yeast coq3 mutant by the rat homologue suggests that yeast and rat synthesize ubiquinone via the s ame early steps in this pathway.