Physiological metabolic analysis and process optimization of hypoxia in promoting coenzyme Q10 biosynthesis and accumulation in Rhodobacter sphaeroides HY01

Coenzyme Q10 fermentation by Rhodobacter sphaeroides (R. sphaeroides) is highly aerobic. However, its biosynthesis and accumulation are paradoxically induced under hypoxic conditions. While oxygen serves as both an induction signal and a key precursor, the mechanisms underlying Coenzyme Q10 accumulation under hypoxia remain elusive, posing a significant bottleneck for yield improvement. This study systematically elucidated these mechanisms through transcriptomic analysis. Results revealed that metabolic pathways for precursor and Coenzyme Q10 biosynthesis were, surprisingly, downregulated under hypoxia. Conversely, genes inhibiting morphological remodeling were downregulated, while those involved in cell membrane biosynthesis were upregulated. Furthermore, a significant positive correlation was observed between cellular morphology and Coenzyme Q10 yield. Specifically, under varying hypoxic conditions, cell morphology and Coenzyme Q10 yield also exhibited strong correlations, with higher yields were associated with larger cell volumes. These findings suggest that R. sphaeroides enhances Coenzyme Q10 accumulation primarily by expanding the cell volume and membrane surface area rather than upregulating biosynthetic pathways. Leveraging this insight, the addition of unsaturated fatty acids further increasing the Coenzyme Q10 yield by 18.9%. This study provides a novel strategy for enhancing Coenzyme Q10 production through morphological engineering and process optimization.