B-cell maturation antigen(BCMA)fused at the C-terminus to the Fc portion of human IgG1(BCMA-Fc)blocks B-cellactivating factor(BAFF)-and proliferation-inducing ligand(APRIL)-mediated B-cell activation,leading to immune disorders.The fusion protein has been cloned and produced by several engineering cell lines,To reduce cost and enhance production,we attempted to express recombinant human BCMA-Fc(rhBCMA-Fc)in Pichia pastoris under the control of the AOX1 methanol-inducible promoter.To produce the target protein with uniform molecular weight and reduced immunogenicity,we mutated 2 predicted N-linked glycosylation sites.The secretory yield was improved by codon optimization of the target gene sequence.After fed-batch fermentation under optimized conditions,the highest yield(207 mg/L)of rhBCMA-Fc was obtained with high productivity(3.45 mg/L/h).The purified functional rhBCMA-Fc possessed high binding affinity to APRIL and dose-dependent inhibition of APRIL-induced proliferative activity in vitro through three-step purification.Thus,this yeast-derived expression method could be a low-cost and effective alternative to the production of rhBCMA-Fc in mammalian cell lines.