Characterization and high‐yield production of non‐N‐glycosylated recombinant human BCMA‐Fc in Pichia pastoris

摘要: B-cell maturation antigen (BCMA) fused at the C-terminus to Fc portion of human IgG1 (BCMA-Fc) blocks activating factor (BAFF) and proliferation-inducing ligand (APRIL)-mediated activation, leading immune disorders. The fusion protein has been cloned produced by several engineering cell lines. To reduce cost enhance production, we attempted express recombinant BCMA-Fc (rhBCMA-Fc) in Pichia pastoris under control AOX1 methanol-inducible promoter. produce target with uniform molecular weight reduced immunogenicity, mutated two predicted N-linked glycosylation sites. secretory yield was improved codon optimization gene sequence. After fed-batch fermentation optimized conditions, highest (207 mg/L) rhBCMA-Fc obtained high productivity (3.45 mg/L/h). purified functional possessed high-binding affinity APRIL dose-dependent inhibition APRIL-induced proliferative activity vitro through three-step purification. Thus, this yeast-derived expression method could be a low-cost effective alternative production mammalian