title: Optimization of a glycoengineered Pichia pastoris cultivation process for commercial antibody production.
abstract: Glycoengineering enabled the production of proteins with human N-linked glycans by Pichia pastoris. This study used a glycoengineered P. pastoris strain which is capable of producing humanized glycoprotein with terminal galactose for monoclonal antibody production. A design of experiments approach was used to optimize the process parameters. Followed by further optimization of the specific methanol feed rate, induction duration, and the initial induction biomass, the resulting process yielded up to 1.6 g/L of monoclonal antibody. This process was also scaled-up to 1,200-L scale, and the process profiles, productivity, and product quality were comparable with 30-L scale. The successful scale-up demonstrated that this glycoengineered P. pastoris fermentation process is a robust and commercially viable process.
authors: Merck & Co., Inc., Bioprocess Research & Development, Rahway, NJ 07065, USA. Jianxin_Ye@merck.com
authors: Jianxin
authors: J
authors: Ye
authors: Jeffrey
authors: J
authors: Ly
authors: Kathryn
authors: K
authors: Watts
authors: Amy
authors: A
authors: Hsu
authors: Andre
authors: A
authors: Walker
authors: Kathleen
authors: K
authors: McLaughlin
authors: Marina
authors: M
authors: Berdichevsky
authors: Bianka
authors: B
authors: Prinz
authors: D
authors: D
authors: Sean Kersey
authors: Marc
authors: M
authors: d'Anjou
authors: David
authors: D
authors: Pollard
authors: Thomas
authors: T
authors: Potgieter
mesh_terms: D000911:Antibodies, Monoclonal / Q000235:genetics / Q000378:metabolism*; D019149:Bioreactors / Q000382:microbiology; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D007218:Industrial Microbiology / Q000379:methods*; D060847:Metabolic Engineering; D000432:Methanol / Q000378:metabolism; D010843:Pichia / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D006023:Glycoproteins; D011994:Recombinant Proteins; D000432:Methanol