Phosphate limitation increases coenzyme Q(10) production in industrial Rhodobacter sphaeroides HY01

Coenzyme Q(10) (CoQ(10)) is an important component of the respiratory chain in humans and some bacteria. As a high-value-added nutraceutical antioxidant, CoQ(10) has excellent capacity to prevent cardiovascular disease. The content of CoQ(10) 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 CoQ(10) overproduction in the HY01 strain. Moreover, under phosphate- limited conditions (decreased phosphate or in the absence of inorganic phosphate addition), CoQ(10) production increased significantly by 12% to220 mg/L, biomass decreased by 12%, and the CoQ(10) productivity of unit cells increased by 27%. In subsequent fed-batch fermentation, CoQ(10) 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 CoQ(10) 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 CoQ(10) production in the HY01. Phosphate limitation induced a pleiotropic effect on cell metabolism, and that improved CoQ(10) biosynthesis efficiency was possibly related to the disturbance of energy metabolism and redox potential.