Benzoic acid inhibits Coenzyme Q biosynthesis in Schizosaccharomyces pombe

Abstract

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 CoQ10is important not only for increasing metabolic knowledge, but also for improving biotechnological production. Herein, we show thatSchizosaccharomyces pombeutilizesp-aminobenzoate (PABA) in addition top-hydroxybenzoate (PHB) as a precursor for CoQ10synthesis. We explored compounds that affect the synthesis of CoQ10and 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 byppt1(coq2) also overcame the inhibition of CoQ biosynthesis by Bz. Inhibition by Bz was efficient inS.pombeandSchizosaccharomyces japonicus, but less so inSaccharomyces cerevisiae,Aureobasidium pullulans, andEscherichia coli. Bz also inhibited aS.pombe ppt1(coq2) deletion strain expressing humanCOQ2, 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.