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

Coenzyme Q₁₀ fermentation by <i>Rhodobacter sphaeroides</i> (<i>R</i>. <i>sphaeroides</i>) 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 <i>R. sphaeroides</i> 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.