Enhanced Production of Poly-?-glutamic Acid by Bacillus subtilis Using Stage-controlled Fermentation and Viscosity Reduction Strategy

In this study, the production of poly-?-glutamic acid (PGA) by Bacillus subtilis using stage-controlled fermentation and viscosity reduction strategy was investigated in detail. Based on the single-factor optimization experiment, temperature (42 degrees C and 37 degrees C), pH (7.0 and uncontrolled), aeration rate (1.2 vvm and 1.0 vvm), and agitation speed (700 rpm and 500 rpm) were selected for the two-stage controlled fermentation (TSCF). The time points for the TSCF of temperature, pH, aeration rate, and agitation speed were set at 18.52 h, 2.82 h, 5.92 h, and 3.62 h, respectively, based on the kinetic analysis. A PGA titer of 19.79 similar to 22.17 g/L was obtained from the TSCF, which did not increase significantly than that (21.25 +/- 1.26 g/L) of non-stage controlled fermentation (NSCF). This may be due to the high viscosity and low dissolved oxygen of the PGA fermentation broth. Thus, the TSCF combined with a viscosity reduction strategy was developed to further improve the production of PGA. The PGA titer reached 25.00 similar to 30.67 g/L, which increased by 17.66 similar to 32.94% to that of NSCF. This study provided a valuable reference for the development of process control strategies for high-viscosity fermentation systems.