The human peptide rhA beta(1-42) was effectively produced through a novel expression system and purification procedure. The peptide rhA beta(1-42) was successfully expressed in Pichia pastoris, the methylotrophic yeast that has never been used as host The cDNA encoding full-length hA beta(1-42) was synthesized with yeast bias codons and cloned into the pPICZ alpha A vector in frame with the yeast alpha-factor secretion signal under the transcriptional control of the AOX1 promoter and integrated into the secreting expression organism P. pastoris strain X33. Production of rhA beta(1-42) through fermentation was further optimized and scaled up in an 80 L fermentor. Secreted rhA beta(1-42) Was purified using a two-step purification scheme: SP Sepharose ion exchange,chromatography and source (TM) 30 RPC. The purification procedure is fast and efficient and reached a recovery of > 93% without loss of activity. The purified rhA beta(1-42) was confirmed by Western blotting analysis and N-terminals amino sequencing analysis. This efficient and cost-effective expression system facilitates large-scale production and purification for recombinant rhA beta(1-42). (C) 2008 Elsevier Inc. All rights reserved.