Improvement of recombinant hirudin production by controlling NH4+ concentration in Pichia pastoris fermentation.
In recombinant Pichia pastoris fermentation for hirudin production in a 5 l fermenter, a new strategy was explored to match the short fermentation time at low NH4+ concentration with decreased hirudin degradation at high NH4+ concentration. A combination of a defined medium containing initial 0.025 m NH4+ with NH4+ addition up to 0.6 m in the growth phase was achieved in both the improvement of hirudin production and the repression of hirudin degradation. Intact and total hirudin reached 2.63 g l(-1) and 4.25 g l(-1), respectively.
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, P.R. China.
Jizhong
J
Yang
Xiangshan
X
Zhou
Yuanxing
Y
Zhang
D018929:Cell Culture Techniques / Q000379:methods*; D049109:Cell Proliferation; D005285:Fermentation / Q000502:physiology; D006629:Hirudins / Q000096:biosynthesis* / Q000235:genetics* / Q000302:isolation & purification; D010843:Pichia / Q000145:classification / Q000502:physiology*; D015202:Protein Engineering / Q000379:methods*; D000644:Quaternary Ammonium Compounds / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification
D006629:Hirudins; D000644:Quaternary Ammonium Compounds; D011994:Recombinant Proteins