Recent Advances in the Expression of Foreign Genes in Pichia pastoris

The Pichia pastoris heterologous gene expression system has been utilized to produce attractive levels of a variety of intracellular and extracellular proteins of interest. Recent advances in our understanding and application of the system have improved its utility even further. These advances include: (1) methods for the construction of P. pastoris strains with multiple copies of A0X1-promoter-driven expression cassettes; (2) mixed-feed culture strategies for high foreign protein volumetric productivity rates; (3) methods to reduce proteolysis of some products in high cell-density culture media; (4) tested procedures for purification of secreted products; and (5) detailed information on the structures of N-linked oligosaccharides on P. pastoris secreted proteins. In this review, these advances along with basic features of the P. pastoris system are described and discussed.

[1]  R. Potenz,et al.  High-level expression, purification, and characterization of recombinant human tumor necrosis factor synthesized in the methylotrophic yeast Pichia pastoris. , 1989, Biochemistry.

[2]  J. Cregg,et al.  Functional characterization of the two alcohol oxidase genes from the yeast Pichia pastoris , 1989, Molecular and cellular biology.

[3]  J. Cregg.  Genetics of Methylotrophic Yeasts , 1987 .

[4]  J. Cregg,et al.  Development of yeast transformation systems and construction of methanol-utilization-defective mutants of Pichia pastori by gene disruption , 1987 .

[5]  T. Gingeras,et al.  Isolation of alcohol oxidase and two other methanol regulatable genes from the yeast Pichia pastoris , 1985, Molecular and cellular biology.

[6]  J. Cregg,et al.  An efficient screen for peroxisome-deficient mutants of Pichia pastoris , 1992, Journal of bacteriology.

[7]  M A Kukuruzinska,et al.  Protein glycosylation in yeast. , 1987, Annual review of biochemistry.

[8]  J. Cregg,et al.  Structural comparison of the Pichia pastoris alcohol oxidase genes , 1989, Yeast.

[9]  C. Goochee,et al.  The Oligosaccharides of Glycoproteins: Bioprocess Factors Affecting Oligosaccharide Structure and their Effect on Glycoprotein Properties , 1991, Bio/Technology.

[10]  J. P. van Dijken,et al.  The significance of peroxisomes in the metabolism of one-carbon compounds in yeasts. , 1983, Advances in microbial physiology.

[11]  J J Clare,et al.  Production of mouse epidermal growth factor in yeast: high-level secretion using Pichia pastoris strains containing multiple gene copies. , 1991, Gene.

[12]  R. Siegel,et al.  Continuous Production of a Novel Lysozyme via Secretion from the Yeast, Pichia pastoris , 1989, Bio/Technology.

[13]  C. Scorer,et al.  Foreign gene expression in yeast: a review , 1992, Yeast.

[14]  J. Tschopp,et al.  Size distribution and general structural features of N‐linked oligosaccharides from the methylotrophic yeast, Pichia pastoris , 1989, Yeast.

[15]  J. Cregg,et al.  High–Level Expression and Efficient Assembly of Hepatitis B Surface Antigen in the Methylotrophic Yeast, Pichia Pastoris , 1987, Bio/Technology.

[16]  R. Siegel,et al.  Methylotrophic yeast Pichia pastoris produced in high-cell-density fermentations with high cell yields as vehicle for recombinant protein production. , 1989, Biotechnology and bioengineering.

[17]  Gustav Ammerer,et al.  Expression of a human gene for interferon in yeast , 1981, Nature.

[18]  T. Vedvick.  Gene expression in yeast: Pichia pastoris. , 1991, Current opinion in biotechnology.

[19]  F. Maley,et al.  Glycoprotein synthesis in yeast. Identification of Man8GlcNAc2 as an essential intermediate in oligosaccharide processing. , 1982, The Journal of biological chemistry.

[20]  J. Tschopp,et al.  Secretion of heterologous proteins from the methylotrophic yeast, Pichia pastoris , 1988 .

[21]  T. Gingeras,et al.  Expression of the lacZ gene from two methanol-regulated promoters in Pichia pastoris. , 1987, Nucleic acids research.

[22]  J. Cregg,et al.  Heterologous gene expression in methylotrophic yeast. , 1991, Biotechnology.

[23]  F. Maley,et al.  Structure of oligosaccharides on Saccharomyces SUC2 invertase secreted by the methylotrophic yeast Pichia pastoris. , 1991, The Journal of biological chemistry.

[24]  J. Cregg,et al.  Development of the methylotrophic yeast, Pichia pastoris, as a host system for the production of foreign proteins , 1988 .

[25]  J. Tschopp,et al.  High-Level Secretion of Glycosylated Invertase in the Methylotrophic Yeast, Pichia Pastoris , 1987, Bio/Technology.

[26]  S. Wagner,et al.  High level expression, purification, and characterization of the Kunitz-type protease inhibitor domain of protease nexin-2/amyloid β-protein precursor , 1992 .

[27]  J. Baratti,et al.  Oxidation of Methanol by the Yeast, Pichia pastoris. Purification and Properties of the Alcohol Oxidase , 1980 .

[28]  R. Buckholz,et al.  Yeast Systems for the Commercial Production of Heterologous Proteins , 1991, Bio/Technology.

[29]  I G Charles,et al.  Recombinant Bordetella pertussis pertactin (P69) from the yeast Pichia pastoris: high-level production and immunological properties. , 1991, Vaccine.

[30]  M. Romanos,et al.  High-Level Expression of Tetanus Toxin Fragment C in Pichia Pastoris Strains Containing Multiple Tandem Integrations of the Gene , 1991, Bio/Technology.