Advances in the Applications of Polyhydroxyalkanoate Nanoparticles for Novel Drug Delivery System

Figure 2

PHB synthesis pathway of R. eutropha and regulatory circuits. In the three-step PHB synthesis pathway, two acetyl-CoA molecules are coupled to form acetoacetyl-CoA in a condensation reaction catalysed by β-ketothiolase. The β-ketothiolase is negatively regulated by the product coenzyme A (HSCoA), which is also a product when acetyl-CoA enters the TCA cycle under nonlimited conditions. The product is subsequently and stereoselectively reduced to (R)-3-hydroxybutyryl-CoA in a reaction catalysed by NADPH-dependent acetoacetyl-CoA reductase. High concentration of NADPH and NADH inhibits the citrate synthase of the TCA cycle, which ensures the availability of acetyl-CoA for the β-ketothiolase. Finally, PHB is synthesized by polymerization of (R)-3-hydroxybutyryl-CoA molecules by the PHB synthase. Hatched arrows indicate negative regulatory effects. Reprinted with permission from Kessler and Witholt [11], Copyright (2001), Elsevier.