Phosphate limitation increases coenzyme Q₁₀ production in industrial Rhodobacter sphaeroides HY01

Coenzyme Q₁₀ (CoQ₁₀) is an important component of the respiratory chain in humans and some bacteria. As a high-value-added nutraceutical antioxidant, CoQ₁₀ has excellent capacity to prevent cardiovascular disease. The content of CoQ₁₀ in the industrial Rhodobacter sphaeroides HY01 is hundreds of folds higher than normal physiological levels. In this study, we found that overexpression or optimization of the synthetic pathway failed CoQ₁₀ overproduction in the HY01 strain. Moreover, under phosphate- limited conditions (decreased phosphate or in the absence of inorganic phosphate addition), CoQ₁₀ production increased significantly by 12% to220 mg/L, biomass decreased by 12%, and the CoQ₁₀ productivity of unit cells increased by 27%. In subsequent fed-batch fermentation, CoQ₁₀ production reached 272 mg/L in the shake-flask fermentation and 1.95 g/L in a 100-L bioreactor under phosphate limitation. Furthermore, to understand the mechanism associated with CoQ₁₀ overproduction under phosphate- limited conditions, the comparatve transcriptome analysis was performed. These results indicated that phosphate limitation combined with glucose fed-batch fermentation represented an effective strategy for CoQ₁₀ production in the HY01. Phosphate limitation induced a pleiotropic effect on cell metabolism, and that improved CoQ₁₀ biosynthesis efficiency was possibly related to the disturbance of energy metabolism and redox potential.