초록
<P>Defined and semi-defined medium-based feeding strategies were developed to enhance recombinant human growth hormone (rhGH) production by Bacillus subtilis BGSC-1A178 (scoC (-)) strain carrying pMK4::pre(subC)::hGH. Defined medium-based feeding strategies were designed by exponential feeding of glucose and (NH4)2HPO4 at two pre-determined specific growth rates, ? 0?=?0.10 and 0.17?h(-1). Semi-defined medium-based feeding strategies were designed by exponential feeding of substrate solution consisting of glucose, (NH4)2HPO4, peptone, and trace?salt solution (PTM1) at three pre-determined specific growth rates, ? 0?=?0.10, 0.17, and 0.25?h(-1). At all the strategies applied, transition cultivation time from batch to fed-batch operation was t T?=?4?h. The highest rhGH concentration was obtained as C rhGH?=?0.5?g?L(-1) with semi-defined medium-based feeding strategy designed with ? 0?=?0.25?h(-1) using feed substrate stock solution containing 200?g?L(-1) glucose, 117?g?L(-1) (NH4)2HPO4, 100?g?L(-1) peptone, and 5?mL?L(-1) PTM1 at t?=?22?h when the cell concentration reached to C X?=?8.29?g L(-1). The overall product and cell yields on glucose were obtained as [Formula: see text]?=?7.21?mg?g(-1) and [Formula: see text]?=?0.12?g?g(-1), respectively. The results indicate the requirement of designing continuous feed stream in fed-batch production to enhance rhGH production by r-B. subtilis.</P>