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 cont...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.展开更多
基金The authors appreciate Dr.Jin Miao for the help to construct engineered strains in Table 1.The author also appreciates Prof.Hongwei Yu for providing plasmid materials.This work was supported by the National Natural Science Foundation of China[31870040,31430002,31720103901]the 111 Project of China[B18022]+2 种基金the Fundamental Research Funds for the Central Universities[22221818014]the Natural Science Foundation of Shandong Province[ZR2017ZB0206]the Shandong Taishan Scholar Award to Lixin Zhang.
文摘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.
