Understanding the effect of foreign gene dosage on the physiology of Pichia pastoris by transcriptional analysis of key genes

Applied Microbiology and Biotechnology

Volumn 89, Issue 4, 2011, Pages 1127-1135

  Zhu, Taicheng ^a,b   Guo, Meijin ^a   Zhuang, Yingping ^a   Chu, Ju ^a   Zhang, Siliang ^a  

^a EAST CHINA UNIVERSITY OF SCIENCE AND TECHNOLOGY   (China)

^b INSTITUTE OF MICROBIOLOGY   (China)

Author keywords

Cell physiology; Gene dosage; Methanol metabolism; mRNA quantitative analysis; Pichia pastoris

Indexed keywords

CELL PHYSIOLOGY; CELLULAR PHYSIOLOGY; COPY NUMBER; ENDOPLASMIC RETICULUM; ENERGY SOURCE; EXPRESSION CASSETTE; EXPRESSION LEVELS; FOREIGN GENES; GENE DOSAGE; METABOLIC PATHWAYS; MRNA LEVEL; P. PASTORIS; PICHIA PASTORIS; QUANTITATIVE ANALYSIS; REAL-TIME PCR; TRANSCRIPTIONAL ANALYSIS; UP-REGULATION; YEAST CELL;

CHEMICAL ANALYSIS; CYTOLOGY; GENE EXPRESSION; METABOLISM; METHANOL; NUCLEIC ACIDS; POLYMERASE CHAIN REACTION; PROTEIN FOLDING; STRAIN;

PHYSIOLOGY;

PREPROINSULIN;

ANTIOXIDANT; CELL ORGANELLE; DEVELOPMENTAL BIOLOGY; ENERGY EFFICIENCY; FUNGUS; GENE EXPRESSION; GENETIC ANALYSIS; METABOLISM; METHANOL; POLYMERASE CHAIN REACTION; PROTEIN; QUANTITATIVE ANALYSIS; YEAST;

ARTICLE; CELL FUNCTION; CONTROLLED STUDY; ENDOPLASMIC RETICULUM; FUNGAL CELL; FUNGAL GENE; FUNGAL METABOLISM; FUNGAL STRAIN; GENE DOSAGE; GENETIC ANALYSIS; NONHUMAN; OXIDATIVE STRESS; PICHIA PASTORIS; PROTEIN FOLDING; REAL TIME POLYMERASE CHAIN REACTION;

GENE DOSAGE; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION, FUNGAL; INSULIN; METABOLIC NETWORKS AND PATHWAYS; PICHIA; RECOMBINANT PROTEINS;

PICHIA PASTORIS; SUS;

EID: 79952539209     PISSN: 01757598     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00253-010-2944-1     Document Type: Article

References (36)

1. Cos O, Serrano A, Montesinos JL, Ferrer P, Cregg JM, Valero F (2005) Combined effect of the methanol utilization (Mut) phenotype and gene dosage on recombinant protein production in Pichia pastoris fed-batch cultures. J Biotechnol 116:321-335 (Pubitemid 40312677)
2. Curvers S, Linnemann J, Klauser T, Wandrey C, Takors R (2002) Recombinant protein production with Pichia pastoris in continuous fermentation - kinetic analysis of growth and product formation. Eng Life Sci 8:229-235
3. Daly R, Hearn MT (2005) Expression of heterologous proteins in Pichia pastoris: a useful experimental tool in protein engineering and production. J Mol Recognit 18:119-138 (Pubitemid 40328574)
4. d'Anjou MC, Daugulis AJ (2001) A rational approach to improving productivity in recombinant Pichia pastoris fermentation. Biotechnol Bioeng 72:1-11
5. Dragosits M, Stadlmann J, Albiol J, Baumann K, Maurer M, Gasser B, Sauer M, Altmann F, Ferrer P, Mattanovich D (2009) The effect of temperature on the proteome of recombinant Pichia pastoris. J Proteome Res 8:1380-1392
6. Gasser B, Maurer M, Rautio J, Sauer M, Bhattacharyya A, Saloheimo M, Penttila M, Mattanovich D (2007) Monitoring of transcriptional regulation in Pichia pastoris under protein production conditions. BMC Genomics 8:179
7. Gasser B, Saloheimo M, Rinas U, Dragosits M, Rodriguez-Carmona E, Baumann K, Giuliani M, Parrilli E, Branduardi P, Lang C, Porro D, Ferrer P, Tutino ML, Mattanovich D, Villaverde A (2008) Protein folding and conformational stress in microbial cells producing recombinant proteins: a host comparative overview. Microb Cell Fact 7:11
8. Gellissen G (2000) Heterologous protein production in methylotrophic yeasts. Appl Microbiol Biotechnol 54:741-750
9. Haynes CM, Titus EA, Cooper AA (2004) Degradation of misfolded proteins prevents ER-derived oxidative stress and cell death. Mol Cell 15:767-776 (Pubitemid 39194906)
10. Hohenblum H, Gasser B, Maurer M, Borth N, Mattanovich D (2004) Effects of gene dosage, promoters, and substrates on unfolded protein stress of recombinant Pichia pastoris. Biotechnol Bioeng 85:367-375 (Pubitemid 38186091)
11. Huo XD, Liu YY, Wang X, Ouyang PK, Niu ZD, Shi YH, Qiu BS (2007) Co-expression of human protein disulfide isomerase (hPDI) enhances secretion of bovine follicle-stimulating hormone (bFSH) in Pichia pastoris. Protein Expr Purif 54:234-239 (Pubitemid 46783603)
12. Inan M, Aryasomayajula D, Sinha J, Meagher MM (2006) Enhancement of protein secretion in Pichia pastoris by overexpression of protein disulfide isomerase. Biotechnol Bioeng 93:771-778
13. + strain. Enzyme Microb Technol 39:936-944
14. + strain in transient continuous cultures. J Biotechnol 130:236-246
15. Kimata Y, Ishiwata-Kimata Y, Yamada S, Kohno K (2006) Yeast unfolded protein response pathway regulates expression of genes for anti-oxidative stress and for cell surface proteins. Genes Cells 11:59-69
16. Kohrer K, Domdey H (1991) Preparation of high molecular weight RNA. Methods Enzymol 194:398-405
17. Liu SH, Chou WI, Sheu CC, Chang MD (2005) Improved secretory production of glucoamylase in Pichia pastoris by combination of genetic manipulations. Biochem Biophys Res Commun 326:817-824
18. -ΔΔ method. Methods 25:402-408
19. Ma Y, Hendershot LM (2001) The unfolding tale of the unfolded protein response. Cell 107:827-830 (Pubitemid 34084974)
20. Malhotra JD, Miao H, Zhang K, Wolfson A, Pennathur S, Pipe SW, Kaufman RJ (2008) Antioxidants reduce endoplasmic reticulum stress and improve protein secretion. Proc Natl Acad Sci 105:18525-18530
21. Mansur M, Cabello C, Hernandez L, Pais J, Varas L, Valdes J, Terrero Y, Hidalgo A, Plana L, Besada V, Garcia L, Lamazares E, Castellanos L, Martinez E (2005) Multiple gene copy number enhances insulin precursor secretion in the yeast Pichia pastoris. Biotechnol Lett 27:339-345 (Pubitemid 40564458)
22. Mattanovich D, Gasser B, Hohenblum H, Sauer M (2004) Stress in recombinant protein producing yeasts. J Biotechnol 113:121-135 (Pubitemid 39237075)
23. Penninckx MJ (2002) An overview on glutathione in Saccharomyces versus non-conventional yeasts. FEMS Yeast Res 2:295-305
24. Perrone GG, Tan SX, Dawes IW (2008) Reactive oxygen species and yeast apoptosis. Biochim Biophys Acta 1783:1354-1368
25. Resina D, Bollok M, Khatri NK, Valero F, Neubauer P, Ferrer P (2007) Transcriptional response of Pichia pastoris in fed-batch cultivations to Rhizopus oryzae lipase production reveals UPR induction. Microb Cell Fact 6:21
26. Scorer CA, Clare JJ, Mccombie WR, Romanos MA, Sreekrishna K (1994) Rapid selection using g418 of high copy number transformants of Pichia pastoris for high-level foreign gene-expression. Biotechnology 12:181-184
27. Sunga AJ, Cregg JM (2004) The Pichia pastoris formaldehyde dehydrogenase gene (FLD1) as a marker for selection of multicopy expression strains of P. pastoris. Gene 330:39-47 (Pubitemid 38490416)
28. Travers KJ, Patil CK, Wodicka L, Lockhart DJ, Weissman JS, Walter P (2000) Functional and genomic analyses reveal an essential coordination between the unfolded protein response and ER-associated degradation. Cell 101:249-258
29. Vad R, Nafstad E, Dahl LA, Gabrielsen OS (2005) Engineering of a Pichia pastoris expression system for secretion of high amounts of intact human parathyroid hormone. J Biotechnol 116:251-260 (Pubitemid 40221854)
30. Vassileva A, Chugh DA, Swaminathan S, Khanna N (2001) Effect of copy number on the expression levels of hepatitis B surface antigen in the methylotrophic yeast Pichia pastoris. Protein Expr Purif 21:71-80 (Pubitemid 32614498)
31. Wen SH, Zhang T, Tan TW (2005) Optimization of the amino acid composition in glutathione fermentation. Process Biochem 40:3474-3479 (Pubitemid 41323927)
32. Xiao AF, Zhou XS, Zhou L, Zhang YX (2006) Improvement of cell viability and hirudin production by ascorbic acid in Pichia pastoris fermentation. Appl Microbiol Biotechnol 72:837-844 (Pubitemid 44454949)
33. Yano T, Takigami E, Yurimoto H, Sakai Y (2009) Yap1-regulated glutathione redox system curtails accumulation of formaldehyde and reactive oxygen species in methanol metabolism of Pichia pastoris. Eukaryot Cell 8:540-549
34. Yurimoto H, Kato N, Sakai Y (2005) Assimilation, dissimilation, and detoxification of formaldehyde, a central metabolic intermediate of methylotrophic metabolism. Chem Rec 5:367-375 (Pubitemid 43499197)
35. Zhu T, Guo M, Sun C, Qian J, Zhuang Y, Chu J, Zhang S (2009a) A systematical investigation on the genetic stability of multi-copy Pichia pastoris strains. Biotechnol Lett 31:679-684
36. Zhu T, Guo M, Tang Z, Zhang M, Zhuang Y, Chu J, Zhang S (2009b) Efficient generation of multi-copy strains for optimizing secretory expression of porcine insulin precursor in yeast Pichia pastoris. J Appl Microbiol 107:954-963