Improvement of Coenzyme Q10 Production: Mutagenesis Induced by High Hydrostatic Pressure Treatment and Optimization of Fermentation Conditions

Abstract

Coenzyme Q10 (CoQ10, ubiquinone), a potent antioxidative dietary supplement, was produced by submerged fermentation using Agrobacterium tumefaciens instead of chemical synthesis or solvent extraction. Agrobacterium tumefaciens 1.2554 was subjected to mutagenesis using a series of treatments including high hydrostatic pressure (HHP) treatment, UV irradiation, and diethyl sulfate (DES) treatment to obtain mutant strains showing higher CoQ10 production than wild-type strains. A mutant strain PK38 with four genetic markers was isolated: the specific CoQ10 content of the mutant strain increased by 52.83% compared with the original strain. Effects of carbon and nitrogen sources on CoQ10 production with PK38 were studied. Sucrose at concentration of 30 g/l was tested as the best carbon source, and yeast extract at concentration of 30 g/l supplemented with 10 g/l of ammonium sulfate was identified to be the most favorable for CoQ10 production using PK38. Fed-batch culture strategy was then used for increasing production of CoQ10 in 5-l fermentor. Using the exponential feeding fed-batch culture of sucrose, cell growth and CoQ10 formation were significantly improved. With this strategy, the final cell biomass, CoQ10 production, and specific CoQ10 production increased by 126.11, 173.12, and 22.76%, respectively, compared to those of batch culture.

Coenzyme Q10 Biosynthesis Established in the Non-Ubiquinone Containing Corynebacterium glutamicum by Metabolic Engineering

“…Biotechnological CoQ10 production was achieved after classical mutagenesis and screening of native CoQ10-producing bacteria like A. tumefaciens and R. sphaeroides , ( Ha et al, 2008 ; Kien et al, 2010 ; Yuan et al, 2012 ). These bacteria were also subjected to metabolic engineering ( Koo et al, 2010 ; Lu et al, 2015 ; Zhang et al, 2018 ; Chen et al, 2019 ) as well as the model bacterium E. coli ( Takahashi et al, 2003 ; Park et al, 2005 ; Zahiri et al, 2006 ).…”

Cellular factories for coenzyme Q10 production

“…Besides R. sphaeroides , it is one of the top producers of CoQ 10 at 6.92–9.6 mg/g DCW [61, 83] (Table 1). Initial attempts to increase its production yield involved selecting cells based on their growth on inhibitory precursor analogues [103]. Later efforts involved targeting the overexpression of IPP pathway genes, especially DXS [60].…”

Coenzyme Q10 and its Effective Sources

“…1) (Xue et al, 2012). CoQ10 also known as ubiquinone or ubiquinone-10 and its active form is ubiquinol, is abundant in plants, animals and microorganisms (Yuan et al, 2012). It plays a crucial role in the transfer of electrons between respiratory complexes of the electron transport chain, located within the inner mitochondrial membrane (Cluis et al, 2012).…”