Benzoic acid inhibits Coenzyme Q biosynthesis in Schizosaccharomyces pombe

• Published in: PloS one 2020-11, Vol.15 (11), p.e0242616
• Main Authors: Nishida, Ikuhisa, Yanai, Ryota, Matsuo, Yasuhiro, Kaino, Tomohiro, Kawamukai, Makoto
• Format: Article
• Language: English
• Subjects: Acids; Benzoic acid; Benzoic Acid - pharmacology; Biology and Life Sciences; Biosynthesis; Chemical properties; Chemical reactions; Chromatography; Coenzyme Q; Dietary supplements; E coli; Electron transport; Environmental science; Enzyme synthesis; Enzymes; Ethanol; Fungi; Gene Expression Regulation, Enzymologic - drug effects; Gene Expression Regulation, Fungal - drug effects; Genes; Glucose; Intermediates; Isoprene; Life sciences; Microbiological research; para-Aminobenzoic acid; Physical Sciences; Physiological aspects; Precursors; Prokaryotes; Quinones; Research and Analysis Methods; Schizosaccharomyces - genetics; Schizosaccharomyces - metabolism; Schizosaccharomyces pombe; Schizosaccharomyces pombe Proteins - biosynthesis; Schizosaccharomyces pombe Proteins - genetics; Transportation systems; Ubiquinone; Ubiquinone - biosynthesis; Ubiquinone - genetics; Ubiquinones; Vitamin B; Yeast; Yeasts (Fungi)
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0242616

Coenzyme Q (CoQ, ubiquinone) is an essential component of the electron transport system in aerobic organisms. Human type CoQ10, which has 10 units of isoprene in its quinone structure, is especially valuable as a food supplement. Therefore, studying the biosynthesis of CoQ10 is important not only for increasing metabolic knowledge, but also for improving biotechnological production. Herein, we show that Schizosaccharomyces pombe utilizes p-aminobenzoate (PABA) in addition to p-hydroxybenzoate (PHB) as a precursor for CoQ10 synthesis. We explored compounds that affect the synthesis of CoQ10 and found benzoic acid (Bz) at >5 μg/mL inhibited CoQ biosynthesis without accumulation of apparent CoQ intermediates. This inhibition was counteracted by incubation with a 10-fold lower amount of PABA or PHB. Overexpression of PHB-polyprenyl transferase encoded by ppt1 (coq2) also overcame the inhibition of CoQ biosynthesis by Bz. Inhibition by Bz was efficient in S. pombe and Schizosaccharomyces japonicus, but less so in Saccharomyces cerevisiae, Aureobasidium pullulans, and Escherichia coli. Bz also inhibited a S. pombe ppt1 (coq2) deletion strain expressing human COQ2, and this strain also utilized PABA as a precursor of CoQ10. Thus, Bz is likely to inhibit prenylation reactions involving PHB or PABA catalyzed by Coq2.