Bacteria synthesize various types of isoprenoid quinones. The widely distributed menaquinone (MK) has been typically associated to anaerobic metabolism, whereas ubiquinone (UQ, also called coenzyme Q = CoQ) is generally considered an aerobic quinone. However, our recent discovery of a UQ biosynthesis pathway independent of O2 supports that UQ may also be involved in anaerobic metabolisms ¹, as recently demonstrated in the case of Pseudomonas aeruginosa ². I will present our latest data on the regulation and biochemistry of the O₂-independent CoQ biosynthesis pathway. I will emphasize how the genomic distribution of CoQ and MK pathways in bacterial species sheds new light on the respective roles of these quinones in various metabolisms.

Besides these differences in quinone contents, the O₂-dependent UQ pathway itself seems quite variable in bacteria. Indeed, we previously demonstrated that bacterial species contain between one and four hydroxylases ³. We coupled biochemical and phylogenetic analyses to demonstrate that the di-iron hydroxylase Coq7 was lost twice independently in proteobacteria and that gene duplication and neo-functionalization of flavin-dependent hydroxylases yielded related enzymes that hydroxylate different positions on the benzene ring of CoQ precursors. These results delineate the evolution of the hydroxylases of the CoQ pathway in bacteria since the appearance of CoQ biosynthesis on Earth, about 2.4 billion years ago.

Finally, we also showed that most UQ biosynthesis proteins form a multi-protein complex in Escherichia coli ⁴ and I will discuss how a better fundamental knowledge of the UQ biosynthesis pathway helped us improve CoQ10 production in Corynebacterium glutamicum, an organism that doesn’t produce CoQ naturally ⁵.

• [1] Pelosi, L. et al. Ubiquinone Biosynthesis over the Entire O2 Range: Characterization of a Conserved O2-Independent Pathway. mBio 10, e01319-19 (2019)
• [2] Vo, C.-D.-T. et al. The O2-independent pathway of ubiquinone biosynthesis is essential for denitrification in Pseudomonas aeruginosa. J Biol Chem 295, 9021–9032 (2020)
• [3] Pelosi, L. et al. Evolution of Ubiquinone Biosynthesis: Multiple Proteobacterial Enzymes with Various Regioselectivities To Catalyze Three Contiguous Aromatic Hydroxylation Reactions. mSystems 1, e00091-16 (2016)
• [4] Hajj Chehade, M. et al. A Soluble Metabolon Synthesizes the Isoprenoid Lipid Ubiquinone. Cell chemical biology 26, 482-492 e7 (2019)
• [5] Burgardt, A., Pelosi, L., Hajj Chehade, M. H., Wendisch, V. F. & Pierrel, F. Rational Engineering of Non-Ubiquinone Containing Coryne-bacterium glutamicum for Enhanced Coenzyme Q10 Production. submitted (2022)