Skip to main content

Advertisement

Log in

CoQ10 a super-vitamin: review on application and biosynthesis

  • Review Article
  • Published:
3 Biotech Aims and scope Submit manuscript

Abstract

Coenzyme Q10 (CoQ) or ubiquinone is found in the biological system which is synthesized by the conjugation of benzoquinone ring with isoprenoid chain of variable length. Coenzyme Q10 supplementation energizes the body and increases body energy production in the form of ATP and helps to treat various human diseases such as cardiomyopathy, muscular dystrophy, periodontal disease, etc. Reports of these potential therapeutic advantages of CoQ10 have resulted in its high market demand, which focus the researchers to work on this molecule and develop better bioprocess methods for commercial level production. At the moment, chemical synthesis, semi-synthetic method as well as bio-production utilizing microbes as biofactory are in use for the synthesis of CoQ10. Chemical synthesis involves use of cheap and easily available precursor molecules such as isoprenol, chloromethylquinone, vinylalane, and solanesol. Chemical synthesis methods due to the use of various solvents and chemicals are less feasible, which limits its application. The microbial production of CoQ10 has added advantages of being produced in optically pure form with high yield using inexpensive medium composition. Several bacteria, e.g., Agrobacterium, Paracoccus, Rhodobacterium, and yeast such as Candida, Rhodotorula are the potent ubiquinone producer. Some alternative biosynthetic pathway for designing of CoQ10 production coupled with metabolic engineering might help to increase CoQ10 production. The most common practiced strategy for strain development for commercial CoQ10 production is through natural isolation and chemical mutagenesis. Here, we have reviewed the chemical, semi-synthetic as well as microbial CoQ10 production in detail.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Acosta MJ, Vazquez Fonseca L, Desbats MA, Cerqua C, Zordan R, Trevisson E et al (2016) Coenzyme Q biosynthesis in health and disease. Biochim Biophys Acta 1857(18):1079–1085

    Article  CAS  PubMed  Google Scholar 

  • Anraku Y (1988) Bacterial electron transport chains. Annu Rev Biochem 57:101–132

    Article  CAS  PubMed  Google Scholar 

  • Artuch R et al (2006) Cerebellar ataxia with coenzyme Q10 deficiency: diagnosis and follow-up after coenzyme Q10 supplementation. J Neurol Sci 246:153–158

    Article  CAS  PubMed  Google Scholar 

  • Asencio C, Rodriguez-Hernandez MA, Briones P, Montoya J, Cortes A, Emperador S et al (2016) Severe encephalopathy associated to pyruvate dehydrogenase mutations and unbalanced coenzyme Q10 content. Eur J Hum Genet 24:367–372

    Article  CAS  PubMed  Google Scholar 

  • Bader MW, Xie T, Yu CA, James CA (2000) Bardwell disulfide bonds are generated by quinone reduction. J BiolChem 275:26082–26088

    CAS  Google Scholar 

  • Balakumaran PA, Meenakshisundaram S (2015) Modeling of process parameters for enhanced production of Coenzyme Q10 from Rhodotorula glutinis. Prep Biochem Biotechnol 45:398–410

    Article  CAS  PubMed  Google Scholar 

  • Beal MF (2004) Mitochondrial dysfunction and oxidative damage in Alzheimer’s and Parkinson’s diseases and coenzyme Q10 as a potential treatment. J Bioenerg Biomembr 36:381–386

    Article  CAS  PubMed  Google Scholar 

  • Belogrudov GI, Lee PT, Jonassen T, Hsu AY, Gin P, Clarke CF (2001) Yeast COQ4 encodes a mitochondrial protein required for coenzyme Q synthesis. Arch Biochem Biophys 392:48–58

    Article  CAS  PubMed  Google Scholar 

  • Campagnolo N, Johnston S, Collatz A, Staines D, Marshall-Gradisnik S (2017) Dietary and nutrition interventions for the therapeutic treatment of chronic fatigue syndrome/myalgic encephalomyelitis: a systematic review. J Hum Nutr Diet 30:247–259

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Caso G, Kelly P, McNurlan MA, Lawson WE (2007) Effect of coenzyme Q10 on myopathic symptoms in patients treated with statins. Am J Cardiol 99:1409–1412

    Article  CAS  PubMed  Google Scholar 

  • Choi GS, Kim YS, Seo JH, Ryu YW (2005) Restricted electron flux increases coenzyme Q10 production in Agrobacterium tumefaciens ATCC4452. Process Biochem 40:3225–3229

    Article  CAS  Google Scholar 

  • Choi J, Ryu Y, Park Y, Seo J (2009) Synergistic effects of chromosomal ispB deletion and dxs overexpression on coenzyme Q10 production in recombinant Escherichia coli expressing Agrobacterium tumefaciens dps gene. J Biotechnol 144:64–69

    Article  CAS  PubMed  Google Scholar 

  • Cluis CP, Ekins A, Narcross L, Jiang H, Gold ND, Burja AM, Martin VJ (2011) Identification of bottlenecks in Escherichia coli engineered for the production of CoQ10. Metab Eng 13:733–744

    Article  CAS  PubMed  Google Scholar 

  • Croteau R, Lange MB, Rujan T, Martin W (2000) Isoprenoid biosynthesis:the evolution of two ancient and distinct pathways across genomes.PronatlacadSci. USA 97:13172–13177

    Article  Google Scholar 

  • Dallner G, Sindelar PJ (2000) Regulation of ubiquinone metabolism. Free Radic Biol Med 29(3–4):285–294

    Article  CAS  PubMed  Google Scholar 

  • Dhanasekaran M, Ren J (2005) The emerging role of coenzyme Q-10 in aging, neurodegeneration, cardiovascular disease, cancer and diabetes mellitus. Curro Neurovasc Res 2:447–459

    Article  CAS  Google Scholar 

  • Fan L, Feng Y, Chen GC, Qin LQ, Fu CL, Chen LH (2017) Effects of coenzyme Q10 supplementation on inflammatory markers: a systematic review and meta-analysis of randomized controlled trials. Pharmacol Res 119:128–136

    Article  CAS  PubMed  Google Scholar 

  • Flowers N, Hartley L, Todkill D, Stranges S, Rees K (2014) Co-enzyme Q10 supplementation for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev 12:CD010405. https://doi.org/10.1002/14651858.CD010405.pub2

    Article  Google Scholar 

  • Fukushima T, Tanaka K, Lim H, Mariyama M (2002) Mechanism of cytotoxicity of Paraquat. Environ Health Prev Med (7): 89–94

  • Genova ML, Lenaz G (2014) Functional role of mitochondrial respiratory supercomplexes. Biochim Biophys Acta 1837:427–443

    Article  CAS  PubMed  Google Scholar 

  • Gin P, Hsu AY, Rothman SC, Jonassen T, Lee PT, Tzagoloff A, Clarke CF (2003) The Saccharomyces cerevisiae COQ6 gene encodes a mitochondrial flavin-dependent monooxygenase required for coenzyme Q biosynthesis. J Biol Chem 278:25308–25316

    Article  CAS  PubMed  Google Scholar 

  • Gorman GS, Chinnery PF, Dimauro S, Hirano M, Koga Y, Mcfarland R et al (2016) Mitochondrial diseases. Nat Rev Dis Primers 2:16080. https://doi.org/10.1038/nrdp.2016.80

    Article  PubMed  Google Scholar 

  • Ha SJ, Kim SY, Seo JH, Oh DK, Lee JK (2007) Optimization of culture conditions and scale-up to pilot and plant scales for coenzyme Q10 production by Agrobacterium tumefaciens. Appl Microbiol Biotechnol 74: 974–980

    Article  CAS  PubMed  Google Scholar 

  • Ha SJ, Kim SY, Seo JH, Sim W, Moon HJ, Lee JK (2008) Lactate increases coenzyme Q10 production by Agrobacterium tumefacians. World J MicrobiolBiotechnol 24:887–890

    Article  CAS  Google Scholar 

  • Hansen IL (1976) Bioenergetics in clinical medicine. Gingival leucocytic deficiencies of coenzyme Q10 in patients with periodontal disease. Res Commun Chempatholpharmacol 14(4):729–738

    CAS  Google Scholar 

  • Herebian D, Seibt A, Smits SHJ, Rodenburg RJ, Mayatepek E, Distelmaier F (2017) 4-Hydroxybenzoic acid restores CoQ10 biosynthesis in human COQ2 deficiency. Ann Clin Transl Neurol 4(12):902–908

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hernández-Camacho JD, Bernier M, Guillermo López-Lluch G, Plácido NP (2018) Coenzyme Q10 supplementation in aging and disease. Front Physiol. https://doi.org/10.3389/fphys.2018.00044

  • Hodgson JM, Watts GF, Playford DA, Burke V, Croft KD (2002) Coenzyme Q10 improves blood pressure and, glycaemic control: a controlled trial in subjects with Type 2 diabetes. Ear J ClinNutl 56:1137–1142

    CAS  Google Scholar 

  • Huang M, Wang Y, Liu J, Mao Z (2011) Multiple strategies for metabolic engineering of Escherichia coli for efficient production of coenzyme Q10. Chin J Chem Eng 19:316–326

    Article  CAS  Google Scholar 

  • Ingledew WJ, Poole RK (1984) The respiratory chains of Escherichia coli. Microbial Rev 48:222–271

    CAS  Google Scholar 

  • Istvan E (2003) Statin inhibition of HMG-CoA reductase: a 3-dimensional view. Atheroscler Suppl 4(1):3–8

    Article  CAS  PubMed  Google Scholar 

  • Jeya M, Moon HJ, Lee JL, Kim IW, Lee JK (2010) Current state of coenzyme Q(10) production and its applications. Appl Microbiol Biotechnol 85(6):1653–1663

    Article  CAS  PubMed  Google Scholar 

  • Johnson A, Gin P, Marbois BN, Hsieh EJ, Wu M, Barros MH, Clarke CF, Tzagoloff A (2005) COQ9, a new gene required for the biosynthesis of coenzyme Q in Saccharomyces cerevisiae. J BiolChem 280:31397–31404

    CAS  Google Scholar 

  • Klingen AR, Palsdottir H, Hunte C, Ullmann GM (2007) Redox-linked protonation state changes in Cytochrome bc1 identified by Poisson–Boltzmann electrostatics calculations. Biochim Biophys Acta 1767: 204–221

  • Kwon O, Kotsakis A, Meganathan R (2000) Ubiquinone (coenzyme Q) biosynthesis. inEscherichia coli: identification of the ubiFgene. FEMS Microbiol Lett 186:157–161

    Article  CAS  PubMed  Google Scholar 

  • Langsjoen PH, Langsjoen PH, Folkers K, Richardson P (1991) Treatment of patients with human immunodeficiency virus infection with coenzyme Q10. In: Folkers K, Littarru GP, Yamagami T (eds) Biomedical and Clinical Aspects of Coenzyme Q, vol 6. Elsevier Science Publishers, New York, pp 409–415

    Google Scholar 

  • Lee SQE, Tan TS, Kawamukai M, Chen ES (2017) Cellular factories for coenzyme Q10 production. Microb Cell Fact (2017): 16–39

  • Lenaz G, Fato R, Formiggini G, Genova ML (2007) The role of Coenzyme Q in mitochondrial electron transport. Mitochondrion 7:S8-S33

    Article  CAS  Google Scholar 

  • Lipshutz BH, Mollard P, Pfeiffer S, Chrisman W (2002) A short, highly efficient synthesis of Coenzyme Q10. J Am ChemSoc 124(48):14282–14283

    Article  CAS  Google Scholar 

  • Lipshutz BH, Lower A, Berl V, Schein K, Wetterich F (2005) An improved synthesis of the “miracle nutrient” coenzyme Q10. Org Lett 7(19):4095–4097

    Article  CAS  PubMed  Google Scholar 

  • Lipshutz BH, Butler T, Lower A, Servesko J (2007) Enhancing regiocontrol in carboaluminations of terminal alkynes.application to the one-pot synthesis of coenzyme Q10. Org Lett 9(19):3737–3740

    Article  CAS  PubMed  Google Scholar 

  • Littarru GP, Tiano L, Belardinelli R, Watts GF (2011) Coenzyme Q10, endothelial function, and cardiovascular disease. BioFactors 37: 366–373

    Article  CAS  PubMed  Google Scholar 

  • Liu J, Wang L, Zhan SY, Xia Y (2011) Coenzyme Q10 for Parkinson’s disease. Cochrane Database Syst Rev 12:CD008150. https://doi.org/10.1002/14651858.CD008150.pub

    Article  Google Scholar 

  • López LC, Schuelke M, Quinzii CM, Kanki T, Rodenburg RJT, Naini A, DiMauro S, Hirano M (2006) Leigh syndrome with nephropathy and CoQ10 deficiency due to decaprenyl diphosphate synthase subunit 2 (PDSS2) mutations. Am J Hum Genet 79:1125–1129

    Article  PubMed  PubMed Central  Google Scholar 

  • Luo M, Yang X, Hu J, Ruan X, Mu F, Fu Y (2017) The Synthesis of Coenzyme Q10. Curr Org Chem 21(6): 489–450

    Article  CAS  Google Scholar 

  • Martin SF, Burón I, Espinosa JC, Castilla J, Villalba JM, Torres JM (2007) Coenzyme Q and proteinllipid oxidation in a BSE-infected transgenic mouse model. Free Radic Bioi Med 42:1723–1729

    Article  CAS  Google Scholar 

  • Meganathan R (2001) Ubiquinone biosynthesis in microorganisms. FEMS Microbiol 203(2):131–139

    Article  CAS  Google Scholar 

  • Miyoshi H (2005) Inhibitor of mitochondrial respiratory enzymes. J pesticidal sci 30(2):120–121

    Article  CAS  Google Scholar 

  • Mollet J, Giurgea I, Schlemmer D, Dallner G, Chretien D, Delahodde A, Bacq D, de Lonlay P, Munnich A, Rötig A (2007) Prenyldiphosphate synthase. subunit IIPDSSJI and OH-benzoate polyprenyltransferase I (COQ2) mutations in ubiquinone deficiency and oxidative phosphorylation disorders. J Clin Invest Mar 117(3):765–772

    Article  CAS  Google Scholar 

  • Müller T, Büttner T, Gholipour AF, Kuhn W (2003) Coenzyme Q10 supplementation provides mild symptomatic benefit in patients with Parkinson’s disease. Neurosci Lett 341(3):201–204

    Article  CAS  PubMed  Google Scholar 

  • Negishi E, Liou S-Y, Xu C, Huo S (2002) A novel, highly selective, and general methodology for the synthesis of 1,5-diene-containing oligoisoprenoids of all possible geometrical combinations exemplified by an iterative and convergent synthesis of Coenzyme Q10. Organic Lett 4(2):261–264

    Article  CAS  Google Scholar 

  • Pahari SK, Ghosh S, Halder S, Jana M (2016) Role of Coenzyme Q10 in human life. RJ PT 9(6):635–640

    Google Scholar 

  • Prakash S, Sunitha J, Hans M (2010) Role of coenzyme Q10 as an antioxidant and bioenergizer in periodontal diseases. Indian J Pharmacol 42(6):334–337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Quinzii CM, Kattah AG, Naini A, Akman HO, Mootha VK, DiMauro S, Hirano M (2005) Coenzyme Q deficiency and cerebellar ataxia associated with an aprataxin mutation. Neurology 64:539–541

    Article  CAS  PubMed  Google Scholar 

  • Quinzii C, Naini A, Salviati L, Trevisson E, Navas P, DiMauro S, Hirano M (2006) A mutation in para-hydroxybenzoatepolyprenyl transferase (COQ2) causes primary Coenzyme Q10 deficiency. Am J Hum Genet 78:345–349

    Article  CAS  PubMed  Google Scholar 

  • Ravada SR, Emani LR, Garaga MR, Meka B, Golakoti T (2009) Synthesis of Coenzyme Q10. Am J Infect Dis 5(2):83–89

    Article  CAS  Google Scholar 

  • Rodriguez-Aguilera JC, Cortes AB, Fernandez-Ayala DJ, Navas P (2017) Biochemical assessment of coenzyme Q10 deficiency. J Clin Med 6:E27. https://doi.org/10.3390/jcm6030027

    Article  CAS  PubMed  Google Scholar 

  • Rousseau G, Desrosiers C, Varin F (1998) A comparison of the effects of lovastatin and pravastatin on ubiquinone tissue levels in rats. Curr Ther Res 59(9):666–679

    Article  CAS  Google Scholar 

  • Thai QD, Adam YH, Jonassen T, Lee PT, Catherine FC (2001) A defect in coenzyme Q biosynthesis is responsible for the respiratory deficiency in Saccharomyces cerevisiae abe1 mutants. J BiolChem 276:18161–18168

    Google Scholar 

  • Tiano L, Belardinelli R, Carnevali P, Principi F, Seddaiu G, Littarru GP (2007) Effect of coenzyme Q10 administration on endothelial function and extra cellular super oxide dismutase in patients with ischaemic heart disease: a double-blind, randomized controlled study. Eur Heart 28(18):2249–2255

    Article  CAS  Google Scholar 

  • Tokdar P, Khora SS (2017) Optimization of fermentation process condition for the production of CoQ10 using Paracoccus denitrificans ATCC 19367 fusant strain PF-P1. Int J Eng Res Technol 6(7):135–143

    Google Scholar 

  • Tokdar P, Vanka R, Ranadive P, George S, Khora SS, Deshmukh SK (2014a) Protoplast fusion technology for improved production of coenzyme Q10 using Paracoccus denitrificans ATCC 19367 mutant strains. Biochem Tech 5(2):685–692

    Google Scholar 

  • Tokdar P, Ranadive P, Kshirsagar R, Khora SS, Deshmukh SK (2014b) Influence of substrate feeding and process parameters on production of coenzyme Q10 Using Paracoccus denitrificans ATCC 19367 mutant strain P-87. Adv Biosci Biotechnol 5:966–977

    Article  Google Scholar 

  • Tokdar P, Sanakal A, Ranadive P, Khora SS, George S, Deshmukh SK (2015) Molecular, physiological and phenotypic characterization of Paracoccus denitrificans ATCC 19367 mutant strain P-87 producing improved coenzyme Q10. Indian J Microbiol 55(2):184–193

    Article  CAS  PubMed  Google Scholar 

  • Tran UC, Marbois B, Gin P, Gulmezian M, Jonassen T, Clarke CF (2006) Complementation of Saccharomyces cerevisiae coq7 mutants by mitochondrial targeting of the Escherichia. coliUbiF polypeptide: two functions of yeast Coq7 polypeptide in coenzyme Q biosynthesis. J Biol Chem 281:16401–16409

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Turunen M, Swiezewska E, Chojnacki T, Sindelar P, Dallner G (2002) Regulatory aspects of coenzyme Q metabolism. Free Radic Res 36:437–443

    Article  CAS  PubMed  Google Scholar 

  • Turunen M, Olsson J, Dallner G (2004) Metabolism and function of coenzyme Q. Biochim Biophys Acta 660(2):171–199

    Article  CAS  Google Scholar 

  • Varela-López A, Giampieri F, Battino M, Quiles JL (2016) Coenzyme Q and its role in the dietary therapy against Aging. Molecules 21(3):373

    Article  CAS  PubMed  Google Scholar 

  • Yasukazu Y, Mieko H, Yoko H, Etsuo N (2006) evaluation of the dietary effects of coenzyme Q in vivo by the oxidative stress marker, hydroxyoctadecadienoic acid and its stereoisomer ratio. Biochim Biophys Acta 1760: 1558–1568

    Article  CAS  Google Scholar 

  • Yoshida H, Kotani Y, Ochiai K, Araki K (1998) Production of ubiquione-10 using bacterium. J Gen ApplMicrobiol 44:19–26

    Article  CAS  Google Scholar 

  • Zhu J, Egawa T, Yeh S-R, Yu L, Yu C-A (2007) Simultaneous reduction of iron-sulfur protein and Cytochrome beL) during ubiquinol oxidation in Cytochrome bc1 complex. Proc Nail AcadSci USA 104:4864–4869

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors thank the Department of Biotechnology (DBT), Government of India, for providing financial support. The authors are thankful to Ms. Karuna Yadav for assisting in the preparation of this review article.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kashyap Kumar Dubey.

Ethics declarations

Conflict of interest

The author declares no competing financial interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shukla, S., Dubey, K.K. CoQ10 a super-vitamin: review on application and biosynthesis. 3 Biotech 8, 249 (2018). https://doi.org/10.1007/s13205-018-1271-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s13205-018-1271-6

Keywords

Navigation