Biosynthesis of poly(4-hydroxybutyrate) in recombinant Escherichia coli grown on glycerol is stimulated by propionic acid

One of the most promising polyhydroxyalkanoates (PHAs) for medical applications is poly(4-hydroxybutyrate) (P4HB) due to its biodegradability, biocompatibility and mechanical properties. Currently, the major hurdle for expanding P4HB applications is the production and recovery cost. In this study, we investigated the stimulating factors for P4HB biosynthesis with the ultimate goal of reducing production cost. We found that addition of propionic acid to the culture medium stimulates the P4HB accumulation in recombinant Escherichia coli JM109 grown on glycerol. This stimulating effect was significantly weakened by addition of exogenous methionine, whereas it was not influenced by addition of cysteine. These results suggest that propionic acid enhances P4HB synthesis by reducing the intracellular methionine pool. Utilizing these findings for P4HB production in batch cultures on glycerol, the volumetric yield of P4HB could be improved 4 fold from 0.9 g/L to 3.7 g/L by adding 2 g/L propionic acid into the medium.