Abstract
Coenzyme Q (CoQ) serves as an electron carrier in aerobic respiration and has become an interesting target for biotechnological production due to its antioxidative effect and benefits in supplementation to patients with various diseases. Here, we review discovery of the pathway with a particular focus on its superstructuration and regulation, and we summarize the metabolic engineering strategies for overproduction of CoQ by microorganisms. Studies in model microorganisms elucidated the details of CoQ biosynthesis and revealed the existence of multiprotein complexes composed of several enzymes that catalyze consecutive reactions in the CoQ pathways of Saccharomyces cerevisiae and Escherichia coli. Recent findings indicate that the identity and the total number of proteins involved in CoQ biosynthesis vary between species, which raises interesting questions about the evolution of the pathway and could provide opportunities for easier engineering of CoQ production. For the biotechnological production, so far only microorganisms have been used that naturally synthesize CoQ10 or a related CoQ species. CoQ biosynthesis requires the aromatic precursor 4-hydroxybenzoic acid and the prenyl side chain that defines the CoQ species. Up to now, metabolic engineering strategies concentrated on the overproduction of the prenyl side chain as well as fine-tuning the expression of ubi genes from the ubiquinone modification pathway, resulting in high CoQ yields. With expanding knowledge about CoQ biosynthesis and exploration of new strategies for strain engineering, microbial CoQ production is expected to improve.
Highlights
Coenzyme Q (CoQ), called ubiquinone, plays an essential role in the respiratory chain of eukaryotes and many prokaryotes
1 3 following, we review CoQ biosynthesis in model microorganisms before focusing on C oQ10 production by different bacteria
The global architecture of CoQ biosynthesis is shared between bacteria and eukaryotes as exemplified by the prototypic pathways from the bacterium E. coli and the yeast S. cerevisiae (Fig. 1)
Summary
Coenzyme Q (CoQ), called ubiquinone, plays an essential role in the respiratory chain of eukaryotes and many prokaryotes. CoQ is composed of a benzoquinone head group conjugated to a polyprenyl chain which length varies between organisms. Saccharomyces cerevisiae and Escherichia coli produce CoQ6 and CoQ8, respectively, whereas humans synthesize CoQ10 (Fig. 1). The most well-known function of CoQ is to transfer electrons and protons in respiratory chains that sustain bioenergetics. CoQ acts as a cofactor in uridine biosynthesis, fatty acid oxidation, and for mitochondrial uncoupling proteins. CoQ possesses antioxidant and lipid-solubility properties that protect lipids and lipoproteins from oxidative damage (Lee et al 2012). The roles of CoQ are numerous and have been reviewed recently (Abby et al 2020; Baschiera et al 2021; Cirilli et al 2021)
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