Parametric continuous feed stream design to fine-tune fed-batch bioreactor performance: recombinant human growth hormone production inBacillus subtilis

Abstract

BACKGROUND Design principles of a fed-batch bioreactor system to fine-tune bioreactor performance by increasing production and productivity are investigated. To enhance the production and productivity in fed-batch fermentation of recombinant human growth hormone (rhGH) by Bacillus subtilis, this work develops a continuous feed stream (CFS) design method with the parameters, cultivation time to switch batch- to fed-batch operation, so called transition time, tT, and specific growth rate, μ. RESULTS Based on batch-bioreactor data for rhGH production by recombinant B. subtilis (scoC−) carrying pMK4::pre(subC)::hGH, three components of the defined medium were determined for continuous feeding. Theoretical analysis and modelling of the fed-batch reactor lead to CFS design, to be applied starting at tT, which is a function of specific growth rate, μ. Transition time tT was optimised experimentally using the batch operation μ value, 0.100 h−1; and the highest rhGH concentration was obtained at tT=4 h. rhGH concentration increased further to 127 mg dm−3, when the CFS flow rate applied was calculated using μ = 0.125 h−1. CONCLUSION The performance of the fermentation process was enhanced by 36% and 8 h shortened cultivation time of t = 16 h, increased the rhGH productivity 2.4-fold compared with batch-fermentation. © 2015 Society of Chemical Industry