초록
<P><B>ABSTRACT</B></P><P><B>BACKGROUND</B></P><P>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 <I>Bacillus subtilis</I>, 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, t<SUB>T</SUB>, and specific growth rate, μ.</P><P><B>RESULTS</B></P><P>Based on batch‐bioreactor data for rhGH production by recombinant <I>B. subtilis</I> (<I>scoC</I><SUP>−</SUP>) carrying pMK4::<I>pre</I>(<I>subC</I>)::<I>hGH</I>, 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 t<SUB>T</SUB>, which is a function of specific growth rate, μ. Transition time t<SUB>T</SUB> was optimised experimentally using the batch operation μ value, 0.100 h<SUP>−1</SUP>; and the highest rhGH concentration was obtained at t<SUB>T</SUB>=4 h. rhGH concentration increased further to 127 mg dm<SUP>−3</SUP>, when the CFS flow rate applied was calculated using μ = 0.125 h<SUP>−1</SUP>.</P><P><B>CONCLUSION</B></P><P>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</P>