title: Pichia pastoris secretes recombinant proteins less efficiently than Chinese hamster ovary cells but allows higher space-time yields for less complex proteins.
abstract: Chinese hamster ovary (CHO) cells are currently the workhorse of the biopharmaceutical industry. However, yeasts such as Pichia pastoris are about to enter this field. To compare their capability for recombinant protein secretion, P. pastoris strains and CHO cell lines producing human serum albumin (HSA) and the 3D6 single chain Fv-Fc anti-HIV-1 antibody (3D6scFv-Fc) were cultivated in comparable fed batch processes. In P. pastoris, the mean biomass-specific secretion rate (qp ) was 40-fold lower for 3D6scFv-Fc compared to HSA. On the contrary, qp was similar for both proteins in CHO cells. When comparing both organisms, the mean qp of the CHO cell lines was 1011-fold higher for 3D6scFv-Fc and 26-fold higher for HSA. Due to the low qp of the 3D6scFv-Fc producing strain, the space-time yield (STY) was 9.6-fold lower for P. pastoris. In contrast, the STY of the HSA producer was 9.2-fold higher compared to CHO cells because of the shorter process time and higher biomass density. The results indicate that the protein secretion machinery of P. pastoris is much less efficient and the secretion rate strongly depends on the complexity of the recombinant protein. However, process efficiency of the yeast system allows higher STYs for less complex proteins.
authors.affiliation: Austrian Centre of Industrial Biotechnology (ACIB GmbH), Vienna, Austria; Department of Biotechnology, University of Natural Resources and Life Sciences, Vienna, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Maccani
authors.forename: Nils
authors.initials: N
authors.lastname: Landes
authors.forename: Gerhard
authors.initials: G
authors.lastname: Stadlmayr
authors.forename: Daniel
authors.initials: D
authors.lastname: Maresch
authors.forename: Christian
authors.initials: C
authors.lastname: Leitner
authors.forename: Michael
authors.initials: M
authors.lastname: Maurer
authors.forename: Brigitte
authors.initials: B
authors.lastname: Gasser
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Ernst
authors.forename: Renate
authors.initials: R
authors.lastname: Kunert
authors.forename: Diethard
authors.initials: D
authors.lastname: Mattanovich
mesh_terms: D000818:Animals; D001709:Biotechnology / Q000379:methods*; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D010843:Pichia / Q000378:metabolism*; D011994:Recombinant Proteins / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism*; D057127:Single-Chain Antibodies / Q000737:chemistry / Q000378:metabolism
chemical_list: D011994:Recombinant Proteins; D057127:Single-Chain Antibodies
keywords: CHO cells; Fed batch; Protein secretion; Recombinant protein production; Volumetric productivity