Identification of 3,4-dihydroxy-5-hexaprenylbenzoic acid as an intermediate in the biosynthesis of ubiquinone-6 by Saccharomyces cerevisiae.
The mutant strain of Saccharomyces cerevisiae E3-24 is unable to synthesize ubiquinone-6. When this mutant is grown in the presence of p-hydroxy[U-14C]benzoate or p-hydroxy[carboxy-14C]benzoate, a radioactive compound accumulates. This new metabolite has been isolated and identified as 3,4-dihydroxy-5-hexaprenylbenzoate (3,4-DHHB). Aerobically grown prototrophic strains of S. cerevisiae were found to contain only low levels of this compound. When strain X963-18C, blocked at homoserine O-transacetylase (in methionine biosynthesis), was deprived of methionine, ubiquinone biosynthesis ceased, and 3,4-DHHB was observed to accumulate. This suggested that S-adenosylmethionine (SAM) could be the methyl donor for 3,4-DHHB. Restoration of methionine to the cultures released this block and resulted in the conversion of 3,4-DHHB to ubiquinone-6, demonstrating a precursor--product relationship. The identification of 3,4-DHHB as an intermediate in ubiquinone biosynthesis in yeast establishes an alternate pathway for ubiquinone biosynthesis in eukaryotes.
D002250:Carbon Radioisotopes; D062385:Hydroxybenzoates / Q000378:metabolism; D013058:Mass Spectrometry; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013729:Terpenes / Q000302:isolation & purification / Q000378:metabolism*; D014451:Ubiquinone / Q000096:biosynthesis*
D002250:Carbon Radioisotopes; D062385:Hydroxybenzoates; D013729:Terpenes; C032165:ubiquinone 6; D014451:Ubiquinone; C032167:3,4-dihydroxy-5-hexaprenylbenzoic acid