Angiostatin production in cultivation of recombinant Pichia pastoris fed with mixed carbon sources.
A recombinant strain of Pichia pastoris with a phenotype of MutS was used to produce angiostatin. Due to the low methanol consumption rate of this strain, both methanol and glycerol feedings, that produced oscillation in dissolved O2 concentration, were used during the expression phase to improve cell growth and angiostatin expression. However, enhanced cell growth led to nitrogen limitation that suppressed further production of angiostatin, but addition of ammonia allowed angiostatin concentration to reach 108 mg l(-1) after an expression period of 96 h. The ratio of consumed glycerol to methanol of 1.5:1 (w/w) in the expression phase suggested that methanol played an important role in the metabolism of carbon sources.
Xie
Jingli
J
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.
Zhang
Li
L
Ye
Qin
Q
Zhou
Qingwei
Q
Xin
Li
L
Du
Peng
P
Gan
Renbao
R
D000641:Ammonia / Q000378:metabolism; D043168:Angiostatins; D002244:Carbon / Q000378:metabolism*; D003001:Cloning, Molecular; D005990:Glycerol / Q000378:metabolism*; D006801:Humans; D000432:Methanol / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D010446:Peptide Fragments / Q000096:biosynthesis* / Q000235:genetics; D010843:Pichia / Q000145:classification / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D010958:Plasminogen / Q000096:biosynthesis* / Q000235:genetics; D011786:Quality Control; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D013045:Species Specificity
D010446:Peptide Fragments; D011994:Recombinant Proteins; D002244:Carbon; D000641:Ammonia; D043168:Angiostatins; D010958:Plasminogen; D005990:Glycerol; D010100:Oxygen; D000432:Methanol