Engineering of protein folding and secretion - Strategies to overcome bottlenecks for efficient production of recombinant proteins

Antioxidants and Redox Signaling

Volumn 21, Issue 3, 2014, Pages 414-437

  Delic, Marizela ^a,b   Göngrich, Rebecca ^a   Mattanovich, Diethard ^a,b   Gasser, Brigitte ^a,b  

^a UNIVERSITY OF NATURAL RESOURCES AND LIFE SCIENCES   (Austria)

^b AUSTRIAN CENTRE OF INDUSTRIAL BIOTECHNOLOGY   (Austria)

Author keywords

[No Author keywords available]

Indexed keywords

CALNEXIN; CHAPERONE; RECOMBINANT PROTEIN;

BACTERIAL TRANSLOCATION; CELL ENGINEERING; CYTOLOGY; CYTOPLASM; DISULFIDE BOND; ENERGY METABOLISM; ESCHERICHIA COLI; GLYCOSYLATION; HUMAN; IN VIVO STUDY; NONHUMAN; OXIDATION REDUCTION REACTION; PRIORITY JOURNAL; PROTEIN AGGREGATION; PROTEIN DEGRADATION; PROTEIN ENGINEERING; PROTEIN EXPRESSION; PROTEIN FOLDING; PROTEIN SECRETION; PROTEIN SYNTHESIS; QUALITY CONTROL; REVIEW; BIOSYNTHESIS; CYTOSOL; ENDOPLASMIC RETICULUM; EUKARYOTIC CELL; GENETICS; METABOLISM;

CYTOSOL; ENDOPLASMIC RETICULUM; ESCHERICHIA COLI; EUKARYOTIC CELLS; HUMANS; PROTEIN ENGINEERING; PROTEIN FOLDING; PROTEOLYSIS; RECOMBINANT PROTEINS;

EID: 84897546101     PISSN: 15230864     EISSN: 15577716     Source Type: Journal    
DOI: 10.1089/ars.2014.5844     Document Type: Review

References (221)

1. Abskharon RN, Ramboarina S, El Hassan H, Gad W, Apostol MI, Giachin G, Legname G, Steyaert J, Messens J, Soror SH, and Wohlkonig A. A novel expression system for production of soluble prion proteins in E. coli. Microb Cell Fact 11: 6, 2012.
2. Agaphonov MO, Plotnikova TA, Fokina AV, Romanova NV, Packeiser AN, Kang HA, and Ter-Avanesyan MD. Inactivation of the Hansenula polymorpha PMR1 gene affects cell viability and functioning of the secretory pathway. FEMS Yeast Res 7: 1145-1152, 2007.
3. Antebi A and Fink GR. The yeast Ca(2 + )-ATPase homologue, PMR1, is required for normal Golgi function and localizes in a novel Golgi-like distribution. Mol Biol Cell 3: 633-654, 1992.
4. Apodaca J, Kim I, and Rao H. Cellular tolerance of prion protein PrP in yeast involves proteolysis and the unfolded protein response. Biochem Biophys Res Commun 347: 319-326, 2006.
5. Arbabi-Ghahroudi M, Tanha J, and MacKenzie R. Prokaryotic expression of antibodies. Cancer Metastasis Rev 24: 501-519, 2005.
6. Argon Y and Simen BB. GRP94, an ER chaperone with protein and peptide binding properties. Semin Cell Dev Biol 10: 495-505, 1999.
7. Arima H, Kinoshita T, Ibrahim HR, Azakami H, and Kato A. Enhanced secretion of hydrophobic peptide fused lysozyme by the introduction of N-glycosylation signal and the disruption of calnexin gene in Saccharomyces cerevisiae. FEBS Lett 440: 89-92, 1998.
8. Arvan P, Zhao X, Ramos-Castaneda J, and Chang A. Secretory pathway quality control operating in Golgi, plasmalemmal, and endosomal systems. Traffic 3: 771-780, 2002.
9. Babour A, Beckerich JM, and Gaillardin C. Identification of an UDP-Glc:glycoprotein glucosyltransferase in the yeast Yarrowia lipolytica. Yeast 21: 11-24, 2004.
10. Babst M, Katzmann DJ, Snyder WB, Wendland B, and Emr SD. Endosome-associated complex, ESCRT-II, recruits transport machinery for protein sorting at the multivesicular body. Dev Cell 3: 283-289, 2002.
11. Bach H, Mazor Y, Shaky S, Shoham-Lev A, Berdichevsky Y, Gutnick DL, and Benhar I. Escherichia coli maltosebinding protein as a molecular chaperone for recombinant intracellular cytoplasmic single-chain antibodies. J Mol Biol 312: 79-93, 2001.
12. Bao WG and Fukuhara H. Secretion of human proteins from yeast: stimulation by duplication of polyubiquitin and protein disulfide isomerase genes in Kluyveromyces lactis. Gene 272: 103-110, 2001.
13. Becker E, Florin L, Pfizenmaier K, and Kaufmann H. An XBP-1 dependent bottle-neck in production of IgG subtype antibodies in chemically defined serum-free Chinese hamster ovary (CHO) fed-batch processes. J Biotechnol 135: 217-223, 2008.
14. Becker E, Florin L, Pfizenmaier K, and Kaufmann H. Evaluation of a combinatorial cell engineering approach to overcome apoptotic effects in XBP-1(s) expressing cells. J Biotechnol 146: 198-206, 2010.
15. Ben Zvi AP and Goloubinoff P. Review: mechanisms of disaggregation and refolding of stable protein aggregates by molecular chaperones. J Struct Biol 135: 84-93, 2001.
16. Berkmen M. Production of disulfide-bonded proteins in Escherichia coli. Protein Expr Purif 82: 240-251, 2012.
17. Berkmen M, Boyd D, and Beckwith J. The nonconsecutive disulfide bond of Escherichia coli phytase (AppA) renders it dependent on the protein-disulfide isomerase, DsbC. J Biol Chem 280: 11387-11394, 2005.
18. Bertolotti A, Zhang Y, Hendershot LM, Harding HP, and Ron D. Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response. Nat Cell Biol 2: 326-332, 2000.
19. Bessette PH, Aslund F, Beckwith J, and Georgiou G. Efficient folding of proteins with multiple disulfide bonds in the Escherichia coli cytoplasm. Proc Natl Acad Sci U S A 96: 13703-13708, 1999.
20. Blum P, Ory J, Bauernfeind J, and Krska J. Physiological consequences of DnaK and DnaJ overproduction in Escherichia coli. J Bacteriol 174: 7436-7444, 1992.
21. Bonangelino CJ, Chavez EM, and Bonifacino JS. Genomic screen for vacuolar protein sorting genes in Saccharomyces cerevisiae. Mol Biol Cell 13: 2486-2501, 2002.
22. Booth C and Koch GL. Perturbation of cellular calcium induces secretion of luminal ER proteins. Cell 59: 729-737, 1989.
23. Borth N, Mattanovich D, Kunert R, and Katinger H. Effect of increased expression of protein disulfide isomerase and heavy chain binding protein on antibody secretion in a recombinant CHO cell line. Biotechnol Prog 21: 106-111, 2005.
24. Brown HC, Gangadharan B, and Doering CB. Enhanced biosynthesis of coagulation factor VIII through diminished engagement of the unfolded protein response. J Biol Chem 286: 24451-24457, 2011.
25. Bruser T. The twin-arginine translocation system and its capability for protein secretion in biotechnological protein production. Appl Microbiol Biotechnol 76: 35-45, 2007.
26. Bryant NJ and Stevens TH. Vacuole biogenesis in Saccharomyces cerevisiae: protein transport pathways to the yeast vacuole. Microbiol Mol Biol Rev 62: 230-247, 1998.
27. Buck TM, Wright CM, and Brodsky JL. The activities and function of molecular chaperones in the endoplasmic reticulum. Semin Cell Dev Biol 18: 751-761, 2007.
28. Butz JA, Niebauer RT, and Robinson AS. Co-expression of molecular chaperones does not improve the heterologous expression of mammalian G-protein coupled receptor expression in yeast. Biotechnol Bioeng 84: 292-304, 2003.
29. Cabibbo A, Pagani M, Fabbri M, Rocchi M, Farmery MR, Bulleid NJ, and Sitia R. ERO1-L, a human protein that favors disulfide bond formation in the endoplasmic reticulum. J Biol Chem 275: 4827-4833, 2000.
30. Calloni G, Chen T, Schermann SM, Chang HC, Genevaux P, Agostini F, Tartaglia GG, Hayer-Hartl M, and Hartl FU. DnaK functions as a central hub in the E. coli chaperone network. Cell Rep 1: 251-264, 2012.
31. Carvalho ND, Arentshorst M, Kooistra R, Stam H, Sagt CM, van den Hondel CA, and Ram AF. Effects of a defective ERAD pathway on growth and heterologous protein production in Aspergillus niger. Appl Microbiol Biotechnol 89: 357-373, 2011.
32. Caspers P, Stieger M, and Burn P. Overproduction of bacterial chaperones improves the solubility of recombinant protein tyrosine kinases in Escherichia coli. Cell Mol Biol (Noisy-le-grand) 40: 635-644, 1994.
33. Chakravarthi S, Jessop CE, and Bulleid NJ. The role of glutathione in disulphide bond formation and endoplasmic- reticulum-generated oxidative stress. EMBO Rep 7: 271-275, 2006.
34. Chang W, Gelman MS, and Prives JM. Calnexindependent enhancement of nicotinic acetylcholine receptor assembly and surface expression. J Biol Chem 272: 28925-28932, 1997.
35. Chen C, Snedecor B, Nishihara JC, Joly JC, McFarland N, Andersen DC, Battersby JE, and Champion KM. High- level accumulation of a recombinant antibody fragment in the periplasm of Escherichia coli requires a triple-mutant (degP prc spr) host strain. Biotechnol Bioeng 85: 463-474, 2004.
36. Chung JY, Lim SW, Hong YJ, Hwang SO, and Lee GM. Effect of doxycycline-regulated calnexin and calreticulin expression on specific thrombopoietin productivity of recombinant Chinese hamster ovary cells. Biotechnol Bioeng 85: 539-546, 2004.
37. Ciplys E, Samuel D, Juozapaitis M, Sasnauskas K, and Slibinskas R. Overexpression of human virus surface glycoprotein precursors induces cytosolic unfolded protein response in Saccharomyces cerevisiae. Microb Cell Fact 10: 37, 2011.
38. Ciplys E, Sasnauskas K, and Slibinskas R. Overexpression of human calnexin in yeast improves measles surface glycoprotein solubility. FEMS Yeast Res 11: 514-523, 2011.
39. Conesa A, Jeenes D, Archer DB, van den Hondel CA, and Punt PJ. Calnexin overexpression increases manganese peroxidase production in Aspergillus niger. Appl Environ Microbiol 68: 846-851, 2002.
40. Cooper AA and Stevens TH. Vps10p cycles between the late-Golgi and prevacuolar compartments in its function as the sorting receptor for multiple yeast vacuolar hydrolases. J Cell Biol 133: 529-541, 1996.
41. Coppock DL and Thorpe C. Multidomain flavindependent sulfhydryl oxidases. Antioxid Redox Signal 8: 300-311, 2006.
42. Coughlan CM, Walker JL, Cochran JC, Wittrup KD, and Brodsky JL. Degradation of mutated bovine pancreatic trypsin inhibitor in the yeast vacuole suggests postendoplasmic reticulum protein quality control. J Biol Chem 279: 15289-15297, 2004.
43. Cudna RE and Dickson AJ. Endoplasmic reticulum signaling as a determinant of recombinant protein expression. Biotechnol Bioeng 81: 56-65, 2003.
44. Damasceno L, Anderson K, Ritter G, Cregg J, Old L, and Batt C. Cooverexpression of chaperones for enhanced secretion of a single-chain antibody fragment in Pichia pastoris. Appl Microbiol Biotechnol 74: 381-389, 2007.
45. Davis R, Schooley K, Rasmussen B, Thomas J, and Reddy P. Effect of PDI overexpression on recombinant protein secretion in CHO cells. Biotechnol Prog 16: 736-743, 2000.
46. de Marco A. Protocol for preparing proteins with improved solubility by co-expressing with molecular chaperones in Escherichia coli. Nat Protoc 2: 2632-2639, 2007.
47. de Marco A. Strategies for successful recombinant expression of disulfide bond-dependent proteins in Escherichia coli. Microb Cell Fact 8: 26, 2009.
48. de Marco A, Deuerling E, Mogk A, Tomoyasu T, and Bukau B. Chaperone-based procedure to increase yields of soluble recombinant proteins produced in E. coli. BMC Biotechnol 7: 32, 2007.
49. de Marco A, Vigh L, Diamant S, and Goloubinoff P. Native folding of aggregation-prone recombinant proteins in Escherichia coli by osmolytes, plasmid- or benzyl alcohol-overexpressed molecular chaperones. Cell Stress Chaperones 10: 329-339, 2005.
50. Debarbieux L and Beckwith J. The reductive enzyme thioredoxin 1 acts as an oxidant when it is exported to the Escherichia coli periplasm. Proc Natl Acad Sci U S A 95: 10751-10756, 1998.
51. Delic M, Rebnegger C, Wanka F, Puxbaum V, Haberhauer-Troyer C, Hann S, Kollensperger G, Mattanovich D, and Gasser B. Oxidative protein folding and unfolded protein response elicit differing redox regulation in endoplasmic reticulum and cytosol of yeast. Free Radic Biol Med 52: 2000-2012, 2012.
52. Delic M, Valli M, Graf AB, Pfeffer M, Mattanovich D, and Gasser B. The secretory pathway: exploring yeast diversity. FEMS Microbiol Rev 37: 872-914, 2013.
53. DeLisa MP, Tullman D, and Georgiou G. Folding quality control in the export of proteins by the bacterial twinarginine translocation pathway. Proc Natl Acad Sci U S A 100: 6115-6120, 2003.
54. Denoncin K and Collet JF. Disulfide bond formation in the bacterial periplasm: major achievements and challenges ahead. Antioxid Redox Signal 19: 63-71, 2013.
55. Derman AI, Prinz WA, Belin D, and Beckwith J. Mutations that allow disulfide bond formation in the cytoplasm of Escherichia coli. Science 262: 1744-1747, 1993.
56. Dorner AJ, Krane MG, and Kaufman RJ. Reduction of endogenous GRP78 levels improves secretion of a heterologous protein in CHO cells. Mol Cell Biol 8: 4063-4070, 1988.
57. Dorner AJ, Wasley LC, and Kaufman RJ. Overexpression of GRP78 mitigates stress induction of glucose regulated proteins and blocks secretion of selective proteins in Chinese hamster ovary cells. EMBO J 11: 1563-1571, 1992.
58. Dunn A, Luz JM, Natalia D, Gamble JA, Freedman RB, and Tuite MF. Protein disulphide isomerase (PDI) is required for the secretion of a native disulphide-bonded protein from Saccharomyces cerevisiae. Biochem Soc Trans 23: 78S, 1995.
59. Dürr G, Strayle J, Plemper R, Elbs S, Klee SK, Catty P, Wolf DH, and Rudolph HK. The medial-Golgi ion pump Pmr1 supplies the yeast secretory pathway with Ca2 + and Mn2 + required for glycosylation, sorting, and endoplasmic reticulum-associated protein degradation. Mol Biol Cell 9: 1149-1162, 1998.
60. Ellgaard L and Ruddock LW. The human protein disulphide isomerase family: substrate interactions and functional properties. EMBO Rep 6: 28-32, 2005.
61. Ellis J. Proteins as molecular chaperones. Nature 328: 378-379, 1987.
62. Feige MJ and Hendershot LM. Disulfide bonds in ER protein folding and homeostasis. Curr Opin Cell Biol 23: 167-175, 2011.
63. Feng Z, Ren J, Zhang H, and Zhang L. Disruption of PMR1 in Kluyveromyces lactis improves secretion of calf prochymosin. J Sci Food Agric 91: 100-103, 2011.
64. Fernández FS, Trombetta SE, Hellman U, and Parodi AJ. Purification to homogeneity of UDP-glucose:glycoprotein glucosyltransferase from Schizosaccharomyces pombe and apparent absence of the enzyme from Saccharomyces cerevisiae. J Biol Chem 269: 30701-30706, 1994.
65. Finnis CJ, Payne T, Hay J, Dodsworth N, Wilkinson D, Morton P, Saxton MJ, Tooth DJ, Evans RW, Goldenberg H, Scheiber-Mojdehkar B, Ternes N, and Sleep D. Highlevel production of animal-free recombinant transferrin from Saccharomyces cerevisiae. Microb Cell Fact 9: 87, 2010.
66. Fourneau JM, Cohen H, and van Endert PM. A chaperoneassisted high yield system for the production of HLA-DR4 tetramers in insect cells. J Immunol Methods 285: 253-264, 2004.
67. Fuller RS, Brake A, and Thorner J. Yeast prohormone processing enzyme (KEX2 gene product) is a Ca2 + -dependent serine protease. Proc Natl Acad Sci U S A 86: 1434-1438, 1989.
68. Ganatra MB, Vainauskas S, Hong JM, Taylor TE, Denson JP, Esposito D, Read JD, Schmeisser H, Zoon KC, Hartley JL, and Taron CH. A set of aspartyl protease-deficient strains for improved expression of heterologous proteins in Kluyveromyces lactis. FEMS Yeast Res 11: 168-178, 2011.
69. Garc?́a-Fruitós E, Martinez-Alonso M, Gonzalez- Montalban N, Valli M, Mattanovich D, and Villaverde A. Divergent genetic control of protein solubility and conformational quality in Escherichia coli. J Mol Biol 374: 195-205, 2007.
70. Garc?́a-Fruitós E, Vázquez E, D?́ez-Gil C, Corchero JL, Seras-Franzoso J, Ratera I, Veciana J, and Villaverde A. Bacterial inclusion bodies: making gold from waste. Trends Biotechnol 30: 65-70, 2012.
71. Gasser B, Maurer M, Gach J, Kunert R, and Mattanovich D. Engineering of Pichia pastoris for improved production of antibody fragments. Biotechnol Bioeng 94: 353-361, 2006.
72. Gasser B, Sauer M, Maurer M, Stadlmayr G, and Mattanovich D. Transcriptomics-based identification of novel factors enhancing heterologous protein secretion in yeasts. Appl Environ Microbiol 73: 6499-6507, 2007.
73. Georgiou G and Segatori L. Preparative expression of secreted proteins in bacteria: status report and future prospects. Curr Opin Biotechnol 16: 538-545, 2005.
74. Goloubinoff P, Gatenby AA, and Lorimer GH. GroE heatshock proteins promote assembly of foreign prokaryotic ribulose bisphosphate carboxylase oligomers in Escherichia coli. Nature 337: 44-47, 1989.
75. Graf A, Dragosits M, Gasser B, and Mattanovich D. Yeast systems biotechnology for the production of heterologous proteins. FEMS Yeast Res 9: 335-348, 2009.
76. Grubb S, Guo L, Fisher EA, and Brodsky JL. Protein disulfide isomerases contribute differentially to the endoplasmic reticulum-associated degradation of apolipoprotein B and other substrates. Mol Biol Cell 23: 520-532, 2012.
77. Gruber CW, Cemazar M, Heras B, Martin JL, and Craik DJ. Protein disulfide isomerase: the structure of oxidative folding. Trends Biochem Sci 31: 455-464, 2006.
78. Guerfal M, Ryckaert S, Jacobs PP, Ameloot P, Van Craenenbroeck K, Derycke R, and Callewaert N. The HAC1 gene from Pichia pastoris: characterization and effect of its overexpression on the production of secreted, surface displayed and membrane proteins. Microb Cell Fact 9: 49, 2010.
79. Hammond C, Braakman I, and Helenius A. Role of Nlinked oligosaccharide recognition, glucose trimming, and calnexin in glycoprotein folding and quality control. Proc Natl Acad Sci U S A 91: 913-917, 1994.
80. Harmsen MM, Bruyne MI, Raué HA, and Maat J. Overexpression of binding protein and disruption of the PMR1 gene synergistically stimulate secretion of bovine prochymosin but not plant thaumatin in yeast. Appl Microbiol Biotechnol 46: 365-370, 1996.
81. Hatahet F, Nguyen VD, Salo KE, and Ruddock LW. Disruption of reducing pathways is not essential for efficient disulfide bond formation in the cytoplasm of E. coli. Microb Cell Fact 9: 67, 2010.
82. Hatahet F and Ruddock LW. Protein disulfide isomerase: a critical evaluation of its function in disulfide bond formation. Antioxid Redox Signal 11: 2807-2850, 2009.
83. Hayano T, Hirose M, and Kikuchi M. Protein disulfide isomerase mutant lacking its isomerase activity accelerates protein folding in the cell. FEBS Lett 377: 505-511, 1995.
84. Heckler EJ, Alon A, Fass D, and Thorpe C. Human quiescin-sulfhydryl oxidase, QSOX1: probing internal redox steps by mutagenesis. Biochemistry 47: 4955-4963, 2008.
85. Hendershot L, Bole D, Köhler G, and Kearney JF. Assembly and secretion of heavy chains that do not associate posttranslationally with immunoglobulin heavy chainbinding protein. J Cell Biol 104: 761-767, 1987.
86. Hermey G. The Vps10p-domain receptor family. Cell Mol Life Sci 66: 2677-2689, 2009.
87. Higgins MK, Demir M, and Tate CG. Calnexin coexpression and the use of weaker promoters increase the expression of correctly assembled Shaker potassium channel in insect cells. Biochim Biophys Acta 1610: 124-132, 2003.
88. Hoffmann A, Bukau B, and Kramer G. Structure and function of the molecular chaperone trigger factor. Biochim Biophys Acta 1803: 650-661, 2010.
89. Hohenblum H, Gasser B, Maurer M, Borth N, and Mattanovich D. Effects of gene dosage, promoters, and substrates on unfolded protein stress of recombinant Pichia pastoris. Biotechnol Bioeng 85: 367-375, 2004.
90. Hong E, Davidson AR, and Kaiser CA. A pathway for targeting soluble misfolded proteins to the yeast vacuole. J Cell Biol 135: 623-633, 1996.
91. Horwich AL, Farr GW, and Fenton WA. GroEL-GroESmediated protein folding. Chem Rev 106: 1917-1930, 2006.
92. Hoseki J, Ushioda R, and Nagata K. Mechanism and components of endoplasmic reticulum-associated degradation. J Biochem 147: 19-25, 2010.
93. Hou J, Osterlund T, Liu Z, Petranovic D, and Nielsen J. Heat shock response improves heterologous protein secretion in Saccharomyces cerevisiae. Appl Microbiol Biotechnol 97: 3559-3568, 2013.
94. Hou J, Tyo K, Liu Z, Petranovic D, and Nielsen J. Engineering of vesicle trafficking improves heterologous protein secretion in Saccharomyces cerevisiae. Metab Eng 14: 120-127, 2012.
95. Hsu TA and Betenbaugh MJ. Coexpression of molecular chaperone BiP improves immunoglobulin solubility and IgG secretion from Trichoplusia ni insect cells. Biotechnol Prog 13: 96-104, 1997.
96. Hwang C, Sinskey AJ, and Lodish HF. Oxidized redox state of glutathione in the endoplasmic reticulum. Science 257: 1496-1502, 1992.
97. Idiris A, Bi K, Tohda H, Kumagai H, and Giga-Hama Y. Construction of a protease-deficient strain set for the fission yeast Schizosaccharomyces pombe, useful for effective production of protease-sensitive heterologous proteins. Yeast 23: 83-99, 2006.
98. Idiris A, Tohda H, Bi KW, Isoai A, Kumagai H, and Giga- Hama Y. Enhanced productivity of protease-sensitive heterologous proteins by disruption of multiple protease genes in the fission yeast Schizosaccharomyces pombe. Appl Microbiol Biotechnol 73: 404-420, 2006.
99. Idiris A, Tohda H, Sasaki M, Okada K, Kumagai H, Giga- Hama Y, and Takegawa K. Enhanced protein secretion from multiprotease-deficient fission yeast by modification of its vacuolar protein sorting pathway. Appl Microbiol Biotechnol 85: 667-677, 2010.
100. Inan M, Aryasomayajula D, Sinha J, and Meagher MM. Enhancement of protein secretion in Pichia pastoris by overexpression of protein disulfide isomerase. Biotechnol Bioeng 93: 771-778, 2006.
101. Iwata T, Tanaka R, Suetsugu M, Ishibashi M, Tokunaga H, Kikuchi M, and Tokunaga M. Efficient secretion of human lysozyme from the yeast, Kluyveromyces lactis. Biotechnol Lett 26: 1803-1808, 2004.
102. Jacobs PP and Callewaert N. N-glycosylation engineering of biopharmaceutical expression systems. Curr Mol Med 9: 774-800, 2009.
103. Jong WS, Sauri A, and Luirink J. Extracellular production of recombinant proteins using bacterial autotransporters. Curr Opin Biotechnol 21: 646-652, 2010.
104. Joønson L, Rehfeld JF, and Johnsen AH. Enhanced peptide secretion by gene disruption of CYM1, a novel protease in Saccharomyces cerevisiae. Eur J Biochem 271: 4788-4797, 2004.
105. Joørgensen MU, Emr SD, and Winther JR. Ligand recognition and domain structure of Vps10p, a vacuolar protein sorting receptor in Saccharomyces cerevisiae. Eur J Biochem 260: 461-469, 1999.
106. Kadokura H and Beckwith J. Mechanisms of oxidative protein folding in the bacterial cell envelope. Antioxid Redox Signal 13: 1231-1246, 2010.
107. Kampinga HH and Craig EA. The HSP70 chaperone machinery: J proteins as drivers of functional specificity. Nat Rev Mol Cell Biol 11: 579-592, 2010.
108. Khan SU and Schroder M. Engineering of chaperone systems and of the unfolded protein response. Cytotechnology 57: 207-231, 2008.
109. Kim JY, Fogarty EA, Lu FJ, Zhu H, Wheelock GD, Henderson LA, and DeLisa MP. Twin-arginine translocation of active human tissue plasminogen activator in Escherichia coli. Appl Environ Microbiol 71: 8451-8459, 2005.
110. Kim JY, Kim YG, and Lee GM. CHO cells in biotechnology for production of recombinant proteins: current state and further potential. Appl Microbiol Biotechnol 93: 917-930, 2012.
111. Kimata Y, Kimata YI, Shimizu Y, Abe H, Farcasanu IC, Takeuchi M, Rose MD, and Kohno K. Genetic evidence for a role of BiP/Kar2 that regulates Ire1 in response to accumulation of unfolded proteins. Mol Biol Cell 14: 2559-2569, 2003.
112. Kitagawa T, Kohda K, Tokuhiro K, Hoshida H, Akada R, Takahashi H, and Imaeda T. Identification of genes that enhance cellulase protein production in yeast. J Biotechnol 151: 194-203, 2011.
113. Klabunde J, Kleebank S, Piontek M, Hollenberg CP, Hellwig S, and Degelmann A. Increase of calnexin gene dosage boosts the secretion of heterologous proteins by Hansenula polymorpha. FEMS Yeast Res 7: 1168-1180, 2007.
114. Klappa P, Hawkins HC, and Freedman RB. Interactions between protein disulphide isomerase and peptides. Eur J Biochem 248: 37-42, 1997.
115. Knittler MR, Dirks S, and Haas IG. Molecular chaperones involved in protein degradation in the endoplasmic reticulum: quantitative interaction of the heat shock cognate protein BiP with partially folded immunoglobulin light chains that are degraded in the endoplasmic reticulum. Proc Natl Acad Sci U S A 92: 1764-1768, 1995.
116. Kohno K. Stress-sensing mechanisms in the unfolded protein response: similarities and differences between yeast and mammals. J Biochem 147: 27-33, 2010.
117. Kolaj O, Spada S, Robin S, and Wall JG. Use of folding modulators to improve heterologous protein production in Escherichia coli. Microb Cell Fact 8: 9, 2009.
118. Ku SC, Ng DT, Yap MG, and Chao SH. Effects of overexpression of X-box binding protein 1 on recombinant protein production in Chinese hamster ovary and NS0 myeloma cells. Biotechnol Bioeng 99: 155-164, 2008.
119. Li W, Schulman S, Dutton RJ, Boyd D, Beckwith J, and Rapoport TA. Structure of a bacterial homologue of vitamin K epoxide reductase. Nature 463: 507-512, 2010.
120. Liu X, Wu D, Wu J, and Chen J. Optimization of the production of Aspergillus niger a-glucosidase expressed in Pichia pastoris. World J Microbiol Biotechnol 29: 533-540, 2013.
121. Lobstein J, Emrich CA, Jeans C, Faulkner M, Riggs P, and Berkmen M. SHuffle, a novel Escherichia coli protein expression strain capable of correctly folding disulfide bonded proteins in its cytoplasm. Microb Cell Fact 11: 56, 2012.
122. Lodi T, Neglia B, and Donnini C. Secretion of human serum albumin by Kluyveromyces lactis overexpressing KlPDI1 and KlERO1. Appl Environ Microbiol 71: 4359-4363, 2005.
123. Lombraña M, Moralejo FJ, Pinto R, and Mart?́n JF. Modulation of Aspergillus awamori thaumatin secretion by modification of bipA gene expression. Appl Environ Microbiol 70: 5145-5152, 2004.
124. Low KO, Muhammad Mahadi N, and Md Illias R. Optimisation of signal peptide for recombinant protein secretion in bacterial hosts. Appl Microbiol Biotechnol 97: 3811-3826, 2013.
125. Malhotra A. Tagging for protein expression. Methods Enzymol 463: 239-258, 2009.
126. Malhotra JD and Kaufman RJ. The endoplasmic reticulum and the unfolded protein response. Semin Cell Dev Biol 18: 716-731, 2007.
127. Malhotra JD, Miao H, Zhang K, Wolfson A, Pennathur S, Pipe SW, and Kaufman RJ. Antioxidants reduce endoplasmic reticulum stress and improve protein secretion. Proc Natl Acad Sci U S A 105: 18525-18530, 2008.
128. Martinez-Alonso M, Garcia-Fruitos E, Ferrer-Miralles N, Rinas U, and Villaverde A. Side effects of chaperone gene co-expression in recombinant protein production. Microb Cell Fact 9: 64, 2010.
129. Melnick LM, Turner BG, Puma P, Price-Tillotson B, Salvato KA, Dumais DR, Moir DT, Broeze RJ, and Avgerinos GC. Characterization of a nonglycosylated single chain urinary plasminogen activator secreted from yeast. J Biol Chem 265: 801-807, 1990.
130. Misselwitz B, Staeck O, and Rapoport TA. J proteins catalytically activate Hsp70 molecules to trap a wide range of peptide sequences. Mol Cell 2: 593-603, 1998.
131. Mogk A, Deuerling E, Vorderwulbecke S, Vierling E, and Bukau B. Small heat shock proteins, ClpB and the DnaK system form a functional triade in reversing protein aggregation. Mol Microbiol 50: 585-595, 2003.
132. Mohan C, Park SH, Chung JY, and Lee GM. Effect of doxycycline-regulated protein disulfide isomerase expression on the specific productivity of recombinant CHO cells: thrombopoietin and antibody. Biotechnol Bioeng 98: 611-615, 2007.
133. Molinari M, Calanca V, Galli C, Lucca P, and Paganetti P. Role of EDEM in the release of misfolded glycoproteins from the calnexin cycle. Science 299: 1397-1400, 2003.
134. Moralejo FJ, Cardoza RE, Gutierrez S, Lombraña M, Fierro F, and Mart?́n JF. Silencing of the aspergillopepsin B (pepB) gene of Aspergillus awamori by antisense RNA expression or protease removal by gene disruption results in a large increase in thaumatin production. Appl Environ Microbiol 68: 3550-3559, 2002.
135. Moralejo FJ, Watson AJ, Jeenes DJ, Archer DB, and Martín JF. A defined level of protein disulfide isomerase expression is required for optimal secretion of thaumatin by Aspergillus awamori. Mol Genet Genomics 266: 246-253, 2001.
136. Mukaiyama H, Tohda H, and Takegawa K. Overexpression of protein disulfide isomerases enhances secretion of recombinant human transferrin in Schizosaccharomyces pombe. Appl Microbiol Biotechnol 86: 1135-1143, 2010.
137. Ng DT, Brown JD, and Walter P. Signal sequences specify the targeting route to the endoplasmic reticulum membrane. J Cell Biol 134: 269-278, 1996.
138. Ngiam C, Jeenes DJ, Punt PJ, Van Den Hondel CA, and Archer DB. Characterization of a foldase, protein disulfide isomerase A, in the protein secretory pathway of Aspergillus niger. Appl Environ Microbiol 66: 775-782, 2000.
139. Nguyen VD, Hatahet F, Salo KE, Enlund E, Zhang C, and Ruddock LW. Pre-expression of a sulfhydryl oxidase significantly increases the yields of eukaryotic disulfide bond containing proteins expressed in the cytoplasm of E. coli. Microb Cell Fact 10: 1, 2011.
140. Nguyen VD, Saaranen MJ, Karala AR, Lappi AK, Wang L, Raykhel IB, Alanen HI, Salo KE, Wang CC, and Ruddock LW. Two endoplasmic reticulum PDI peroxidases increase the efficiency of the use of peroxide during disulfide bond formation. J Mol Biol 406: 503-515, 2011.
141. Ni Y and Chen R. Extracellular recombinant protein production from Escherichia coli. Biotechnol Lett 31: 1661-1670, 2009.
142. Nishihara K, Kanemori M, Yanagi H, and Yura T. Overexpression of trigger factor prevents aggregation of recombinant proteins in Escherichia coli. Appl Environ Microbiol 66: 884-889, 2000.
143. Nishimiya D, Ogura Y, Sakurai H, and Takahashi T. Identification of antibody-interacting proteins that contribute to the production of recombinant antibody in mammalian cells. Appl Microbiol Biotechnol 96: 971-979, 2012.
144. Ohya T, Hayashi T, Kiyama E, Nishii H, Miki H, Kobayashi K, Honda K, Omasa T, and Ohtake H. Improved production of recombinant human antithrombin III in Chinese hamster ovary cells by ATF4 overexpression. Biotechnol Bioeng 100: 317-324, 2008.
145. Omasa T, Takami T, Ohya T, Kiyama E, Hayashi T, Nishii H, Miki H, Kobayashi K, Honda K, and Ohtake H. Overexpression of GADD34 enhances production of recombinant human antithrombin III in Chinese hamster ovary cells. J Biosci Bioeng 106: 568-573, 2008.
146. Pagani M, Fabbri M, Benedetti C, Fassio A, Pilati S, Bulleid NJ, Cabibbo A, and Sitia R. Endoplasmic reticulum oxidoreductin 1-lbeta (ERO1-Lbeta), a human gene induced in the course of the unfolded protein response. J Biol Chem 275: 23685-23692, 2000.
147. Pakula TM, Laxell M, Huuskonen A, Uusitalo J, Saloheimo M, and Penttila M. The effects of drugs inhibiting protein secretion in the filamentous fungus Trichoderma reesei. Evidence for down-regulation of genes that encode secreted proteins in the stressed cells. J Biol Chem 278: 45011-45020, 2003.
148. Pan KL, Hsiao HC, Weng CL, Wu MS, and Chou CP. Roles of DegP in prevention of protein misfolding in the periplasm upon overexpression of penicillin acylase in Escherichia coli. J Bacteriol 185: 3020-3030, 2003.
149. Parlati F, Dominguez M, Bergeron JJ, and Thomas DY. Saccharomyces cerevisiae CNE1 encodes an endoplasmic reticulum (ER) membrane protein with sequence similarity to calnexin and calreticulin and functions as a constituent of the ER quality control apparatus. J Biol Chem 270: 244-253, 1995.
150. Payne T, Finnis C, Evans LR, Mead DJ, Avery SV, Archer DB, and Sleep D. Modulation of chaperone gene expression in mutagenized Saccharomyces cerevisiae strains developed for recombinant human albumin production results in increased production of multiple heterologous proteins. Appl Environ Microbiol 74: 7759-7766, 2008.
151. Peng RW, Abellan E, and Fussenegger M. Differential effect of exocytic SNAREs on the production of recombinant proteins in mammalian cells. Biotechnol Bioeng 108: 611-620, 2011.
152. Peng RW and Fussenegger M. Molecular engineering of exocytic vesicle traffic enhances the productivity of Chinese hamster ovary cells. Biotechnol Bioeng 102: 1170-1181, 2009.
153. Pfeffer M, Maurer M, Stadlmann J, Grass J, Delic M, Altmann F, and Mattanovich D. Intracellular interactome of secreted antibody Fab fragment in Pichia pastoris reveals its routes of secretion and degradation. Appl Microbiol Biotechnol 93: 2503-2512, 2012.
154. Pohl S and Harwood CR. Heterologous protein secretion by bacillus species from the cradle to the grave. Adv Appl Microbiol 73: 1-25, 2010.
155. Powers SL and Robinson AS. PDI improves secretion of redox-inactive beta-glucosidase. Biotechnol Prog 23: 364-369, 2007.
156. PrinzWA, Aslund F, Holmgren A, and Beckwith J. The role of the thioredoxin and glutaredoxin pathways in reducing protein disulfide bonds in the Escherichia coli cytoplasm. J Biol Chem 272: 15661-15667, 1997.
157. Qiu J, Swartz JR, and Georgiou G. Expression of active human tissue-type plasminogen activator in Escherichia coli. Appl Environ Microbiol 64: 4891-4896, 1998.
158. Rampelt H, Mayer MP, and Bukau B. Nucleotide exchange factors for Hsp70 chaperones. Methods Mol Biol 787: 83-91, 2011.
159. Reed B and Chen R. Biotechnological applications of bacterial protein secretion: From therapeutics to biofuel production. Res Microbiol 164: 675-682, 2013.
160. Ren G and Bardwell JC. Engineered pathways for correct disulfide bond oxidation. Antioxid Redox Signal 14: 2399-2412, 2011.
161. Rietsch A, Bessette P, Georgiou G, and Beckwith J. Reduction of the periplasmic disulfide bond isomerase, DsbC, occurs by passage of electrons from cytoplasmic thioredoxin. J Bacteriol 179: 6602-6608, 1997.
162. Ritz D, Lim J, Reynolds CM, Poole LB, and Beckwith J. Conversion of a peroxiredoxin into a disulfide reductase by a triplet repeat expansion. Science 294: 158-160, 2001.
163. Robinson AS, Bockhaus JA, Voegler AC, and Wittrup KD. Reduction of BiP levels decreases heterologous protein secretion in Saccharomyces cerevisiae. J Biol Chem 271: 10017-10022, 1996.
164. Robinson AS, Hines V, and Wittrup KD. Protein disulfide isomerase overexpression increases secretion of foreign proteins in Saccharomyces cerevisiae. Biotechnology (N Y) 12: 381-384, 1994.
165. Ruohonen L, Toikkanen J, Tieaho V, Outola M, Soderlund H, and Keranen S. Enhancement of protein secretion in Saccharomyces cerevisiae by overproduction of Sso protein, a late-acting component of the secretory machinery. Yeast 13: 337-351, 1997.
166. Sagt CM, Mü ller WH, Boonstra J, Verkleij AJ, and Verrips CT. Impaired secretion of a hydrophobic cutinase by Saccharomyces cerevisiae correlates with an increased association with immunoglobulin heavy-chain binding protein (BiP). Appl Environ Microbiol 64: 316-324, 1998.
167. Salinas G, Pellizza L, Margenat M, Flo M, and Fernandez C. Tuned Escherichia coli as a host for the expression of disulfide-rich proteins. Biotechnol J 6: 686-699, 2011.
168. Schierle CF, Berkmen M, Huber D, Kumamoto C, Boyd D, and Beckwith J. The DsbA signal sequence directs efficient, cotranslational export of passenger proteins to the Escherichia coli periplasm via the signal recognition particle pathway. J Bacteriol 185: 5706-5713, 2003.
169. Schlapschy M and Skerra A. Periplasmic chaperones used to enhance functional secretion of proteins in E. coli. Methods Mol Biol 705: 211-224, 2011.
170. Sevier CS and Kaiser CA. Conservation and diversity of the cellular disulfide bond formation pathways. Antioxid Redox Signal 8: 797-811, 2006.
171. Sevier CS and Kaiser CA. Formation and transfer of disulphide bonds in living cells. Nat Rev Mol Cell Biol 3: 836-847, 2002.
172. Shen J, Chen X, Hendershot L, and Prywes R. ER stress regulation of ATF6 localization by dissociation of BiP/ GRP78 binding and unmasking of Golgi localization signals. Dev Cell 3: 99-111, 2002.
173. Shusta E, Raines R, Plückthun A, and Wittrup K. Increasing the secretory capacity of Saccharomyces cerevisiae for production of single-chain antibody fragments. Nat Biotechnol 16: 773-777, 1998.
174. Smith JD, Tang BC, and Robinson AS. Protein disulfide isomerase, but not binding protein, overexpression enhances secretion of a non-disulfide-bonded protein in yeast. Biotechnol Bioeng 85: 340-350, 2004.
175. Sohn YS, Park CS, Lee SB, and Ryu DD. Disruption of PMR1, encoding a Ca2 + -ATPase homolog in Yarrowia lipolytica, affects secretion and processing of homologous and heterologous proteins. J Bacteriol 180: 6736-6742, 1998.
176. Sonoda H, Kumada Y, Katsuda T, and Yamaji H. Functional expression of single-chain Fv antibody in the cytoplasm of Escherichia coli by thioredoxin fusion and co-expression of molecular chaperones. Protein Expr Purif 70: 248-253, 2010.
177. Stadlmayr G, Benakovitsch K, Gasser B, Mattanovich D, and Sauer M. Genome-scale analysis of library sorting (GALibSo): Isolation of secretion enhancing factors for recombinant protein production in Pichia pastoris. Biotechnol Bioeng 105: 543-555, 2010.
178. Steiner D, Forrer P, Stumpp MT, and Pluckthun A. Signal sequences directing cotranslational translocation expand the range of proteins amenable to phage display. Nat Biotechnol 24: 823-831, 2006.
179. Stewart EJ, Aslund F, and Beckwith J. Disulfide bond formation in the Escherichia coli cytoplasm: an in vivo role reversal for the thioredoxins. EMBO J 17: 5543-5550, 1998.
180. Strayle J, Pozzan T, and Rudolph HK. Steady-state free Ca(2 + ) in the yeast endoplasmic reticulum reaches only 10 microM and is mainly controlled by the secretory pathway pump pmr1. EMBO J 18: 4733-4743, 1999.
181. Suzuki CK, Bonifacino JS, Lin AY, Davis MM, and Klausner RD. Regulating the retention of T-cell receptor alpha chain variants within the endoplasmic reticulum: Ca(2 + )-dependent association with BiP. J Cell Biol 114: 189-205, 1991.
182. Takegawa K, DeWald DB, and Emr SD. Schizosaccharomyces pombe Vps34p, a phosphatidylinositol-specific PI 3-kinase essential for normal cell growth and vacuole morphology. J Cell Sci 108 (Pt 12): 3745-3756, 1995.
183. Tate CG, Whiteley E, and Betenbaugh MJ. Molecular chaperones stimulate the functional expression of the cocaine-sensitive serotonin transporter. J Biol Chem 274: 17551-17558, 1999.
184. Teng CY, Chang SL, van Oers MM, and Wu TY. Enhanced protein secretion from insect cells by co-expression of the chaperone calreticulin and translation initiation factor eIF4E. Mol Biotechnol 54: 68-78, 2013.
185. Thie H, Schirrmann T, Paschke M, Dubel S, and Hust M. SRP and Sec pathway leader peptides for antibody phage display and antibody fragment production in E. coli. N Biotechnol 25: 49-54, 2008.
186. Thorpe C and Coppock DL. Generating disulfides in multicellular organisms: emerging roles for a new flavoprotein family. J Biol Chem 282: 13929-13933, 2007.
187. Tien AC, Rajan A, Schulze KL, Ryoo HD, Acar M, Steller H, and Bellen HJ. Ero1L, a thiol oxidase, is required for Notch signaling through cysteine bridge formation of the Lin12-Notch repeats in Drosophila melanogaster. J Cell Biol 182: 1113-1125, 2008.
188. Tigges M and Fussenegger M. Xbp1-based engineering of secretory capacity enhances the productivity of Chinese hamster ovary cells. Metab Eng 8: 264-272, 2006.
189. Toikkanen J, Sundqvist L, and Keränen S. Kluyveromyces lactis SSO1 and SEB1 genes are functional in Saccharomyces cerevisiae and enhance production of secreted proteins when overexpressed. Yeast 21: 1045-1055, 2004.
190. Trombetta SE and Parodi AJ. Purification to apparent homogeneity and partial characterization of rat liver UDPglucose: glycoprotein glucosyltransferase. J Biol Chem 267: 9236-9240, 1992.
191. Tu B and Weissman J. Oxidative protein folding in eukaryotes: mechanisms and consequences. J Cell Biol 164: 341-346, 2004.
192. Uccelletti D, Farina F, Mancini P, and Palleschi C. KlPMR1 inactivation and calcium addition enhance secretion of non-hyperglycosylated heterologous proteins in Kluyveromyces lactis. J Biotechnol 109: 93-101, 2004.
193. Vad R, Nafstad E, Dahl L, and Gabrielsen O. Engineering of a Pichia pastoris expression system for secretion of high amounts of intact human parathyroid hormone. J Biotechnol 116: 251-260, 2005.
194. Valkonen M, Penttilä M, and Saloheimo M. Effects of inactivation and constitutive expression of the unfoldedprotein response pathway on protein production in the yeast Saccharomyces cerevisiae. Appl Environ Microbiol 69: 2065-2072, 2003.
195. Valkonen M, Ward M, Wang H, Penttilä M, and Saloheimo M. Improvement of foreign-protein production in Aspergillus niger var. awamori by constitutive induction of the unfolded-protein response. Appl Environ Microbiol 69: 6979-6986, 2003.
196. van der Heide M, Hollenberg CP, van der Klei IJ, and Veenhuis M. Overproduction of BiP negatively affects the secretion of Aspergillus niger glucose oxidase by the yeast Hansenula polymorpha. Appl Microbiol Biotechnol 58: 487-494, 2002.
197. van Gemeren IA, Beijersbergen A, van den Hondel CA, and Verrips CT. Expression and secretion of defined cutinase variants by Aspergillus awamori. Appl Environ Microbiol 64: 2794-2799, 1998.
198. Vashist S and Ng DT. Misfolded proteins are sorted by a sequential checkpoint mechanism of ER quality control. J Cell Biol 165: 41-52, 2004.
199. Vazquez-Martinez R, Diaz-Ruiz A, Almabouada F, Rabanal-Ruiz Y, Gracia-Navarro F, and Malagon MM. Revisiting the regulated secretory pathway: from frogs to human. Gen Comp Endocrinol 175: 1-9, 2012.
200. Veggiani G and de Marco A. Improved quantitative and qualitative production of single-domain intrabodies mediated by the co-expression of Erv1p sulfhydryl oxidase. Protein Expr Purif 79: 111-114, 2011.
201. Vembar SS and Brodsky JL. One step at a time: endoplasmic reticulum-associated degradation. Nat Rev Mol Cell Biol 9: 944-957, 2008.
202. Vera A, Aris A, Carrio M, Gonzalez-Montalban N, and Villaverde A. Lon and ClpP proteases participate in the physiological disintegration of bacterial inclusion bodies. J Biotechnol 119: 163-171, 2005.
203. Wang CC and Tsou CL. Protein disulfide isomerase is both an enzyme and a chaperone. FASEB J 7: 1515-1517, 1993.
204. Ware FE, Vassilakos A, Peterson PA, Jackson MR, Lehrman MA, and Williams DB. The molecular chaperone calnexin binds Glc1Man9GlcNAc2 oligosaccharide as an initial step in recognizing unfolded glycoproteins. J Biol Chem 270: 4697-4704, 1995.
205. Wentz AE and Shusta EV. A novel high-throughput screen reveals yeast genes that increase secretion of heterologous proteins. Appl Environ Microbiol 73: 1189-1198, 2007.
206. Werten MW and de Wolf FA. Reduced proteolysis of secreted gelatin and Yps1-mediated alpha-factor leader processing in a Pichia pastoris kex2 disruptant. Appl Environ Microbiol 71: 2310-2317, 2005.
207. Whyteside G, Alcocer MJ, Kumita JR, Dobson CM, Lazarou M, Pleass RJ, and Archer DB. Native-state stability determines the extent of degradation relative to secretion of protein variants from Pichia pastoris. PLoS One 6: e22692, 2011.
208. Wileman T, Kane LP, Carson GR, and Terhorst C. Depletion of cellular calcium accelerates protein degradation in the endoplasmic reticulum. J Biol Chem 266: 4500-4507, 1991.
209. Xu P, Raden D, Doyle FJ, and Robinson AS. Analysis of unfolded protein response during single-chain antibody expression in Saccaromyces cerevisiae reveals different roles for BiP and PDI in folding. Metab Eng 7: 269-279, 2005.
210. Xu Y, Lewis D, and Chou CP. Effect of folding factors in rescuing unstable heterologous lipase B to enhance its overexpression in the periplasm of Escherichia coli. Appl Microbiol Biotechnol 79: 1035-1044, 2008.
211. Yamamoto Y, Ritz D, Planson AG, Jonsson TJ, FaulknerMJ, Boyd D, Beckwith J, and Poole LB. Mutant AhpC peroxiredoxins suppress thiol-disulfide redox deficiencies and acquire deglutathionylating activity. Mol Cell 29: 36-45, 2008.
212. Yao XQ, Zhao HL, Xue C, Zhang W, Xiong XH, Wang ZW, Li XY, and Liu ZM. Degradation of HSAAX15( R13K) when expressed in Pichia pastoris can be reduced via the disruption of YPS1 gene in this yeast. J Biotechnol 139: 131-136, 2009.
213. Yoon J, Aishan T, Maruyama J, and Kitamoto K. Enhanced production and secretion of heterologous proteins by the filamentous fungus Aspergillus oryzae via disruption of vacuolar protein sorting receptor gene Aovps10. Appl Environ Microbiol 76: 5718-5727, 2010.
214. Yoon SH, Kim SK, and Kim JF. Secretory production of recombinant proteins in Escherichia coli. Recent Pat Biotechnol 4: 23-29, 2010.
215. Young CL, Yuraszeck T, and Robinson AS. Decreased secretion and unfolded protein response upregulation. Methods Enzymol 491: 235-260, 2011.
216. Zhang L, Wu G, Tate CG, Lookene A, and Olivecrona G. Calreticulin promotes folding/dimerization of human lipoprotein lipase expressed in insect cells (sf21). J Biol Chem 278: 29344-29351, 2003.
217. Zhang W, Zhao HL, Xue C, Xiong XH, Yao XQ, Li XY, Chen HP, and Liu ZM. Enhanced secretion of heterologous proteins in Pichia pastoris following overexpression of Saccharomyces cerevisiae chaperone proteins. Biotechnol Prog 22: 1090-1095, 2006.
218. Zhao HL, Xue C, Wang Y, Duan QF, Xiong XH, Yao XQ, and Liu ZM. Disruption of Pichia pastoris PMR1 gene decreases its folding capacity on human serum albumin and interferon-alpha2b fusion protein. Yeast 25: 279-286, 2008.
219. Zimmermann R, Eyrisch S, Ahmad M, and Helms V. Protein translocation across the ER membrane. Biochim Biophys Acta 1808: 912-924, 2011.
220. Zito E, Chin KT, Blais J, Harding HP, and Ron D. ERO1- beta, a pancreas-specific disulfide oxidase, promotes insulin biogenesis and glucose homeostasis. J Cell Biol 188: 821-832, 2010.
221. Zito E, Melo EP, Yang Y, Wahlander Å , Neubert TA, and Ron D. Oxidative protein folding by an endoplasmic reticulum-localized peroxiredoxin. Mol Cell 40: 787-797, 2010.