Regulatory effects on central carbon metabolism from poly-3-hydroxybutryate synthesis

To understand the regulatory mechanisms that resulted in these macroscopic changes, we used a flux balance analysis model to analyze intracellular redox conditions. Our model shows that under N-limited conditions, synthesis of PHB creates excess reducing equivalents. Cells, under these conditions, secrete more reduced metabolites in order to recycle reducing equivalents. By switching to a more oxidized substrate (gluconate) that decreased excess reducing equivalents, PHB flux yield increased 1.6 fold compared to glucose-fed fermentations. High flux of PHB (~1.2 mmol/g DCW h) was maintained under these steady-state, oxidized conditions. These results imply redox imbalance is a driving force in industrial production of PHB, and substrates that are more oxidized than glucose can increase productivity.