Design of Bacterial Vector Systems for the Production of Recombinant Proteins in Escherichia coli

  • Mergulhao (Centro de Engenharia Biologica e Quimica, Instituto Superior Tecnico) ;
  • Filipe J.M. (Centro de Engenharia Biologica e Quimica, Instituto Superior Tecnico) ;
  • Gabriel A. Monteiro (Centro de Engenharia Biologica e Quimica, Instituto Superior Tecnico) ;
  • Joaquim M.S. Cabral (Centro de Engenharia Biologica e Quimica, Instituto Superior Tecnico) ;
  • M. Angela Taipa (Centro de Engenharia Biologica e Quimica, Instituto Superior Tecnico)
  • Published : 2004.02.01

Abstract

More than twenty years have passed since the approval of the first recombinant DNA product for therapeutic use (recombinant human insulin, 1982). However, the biotechnology industry is still facing a shortage of manufacturing capacity due to the increasing demand of therapeutic proteins. This demand has prompted the search for a growing number of biological production systems but, nevertheless, the Gram-negative bacterium Escherichia coli remains one of the most attractive production hosts. This review highlights the most important features and developments of plasmid vector design, emphasizing the different reported strategies for improving the expression and secretion of heterologous proteins using the cellular machinery of E. coli.

Keywords

References

  1. Abrahmsen, L., T. Moks, B. Nilsson, and M. Uhlen. 1986. Secretion of heterologous gene products to the culture medium of Escherichia coli. Nucleic Acids Res. 14: 7487- 7500
  2. Andersen, D. C. and L. Krummen. 2002. Recombinant protein expression for therapeutic applications. Curr. Opin. Biotechnol. 13: 117-123
  3. Andersson, H. and G. von Heijne. 1991. A 30-residue-long “export initiation domain” adjacent to the signal sequence is critical for protein translocation across the inner membrane of Escherichia coli. Proc. Natl. Acad. Sci. USA 88: 9751- 9754
  4. Baker, K. N., M. H. Rendall, A. Patel, P. Boyd, M. Hoare, R. B. Freedman, and D. C. James. 2002. Rapid monitoring of recombinant protein products: A comparison of current technologies. Trends Biotechnol. 20: 149-156
  5. Balbas, P. 2001. Understanding the art of producing protein and nonprotein molecules in Escherichia coli. Mol. Biotechnol. 19: 251-267
  6. Balbas, P. and F. Bolivar. 1990. Design and construction of expression plasmid vectors in Escherichia coli. Methods Enzymol. 185: 14-37
  7. Balbas, P. and G. Gosset. 2001. Chromosomal editing in Escherichia coli. Vectors for DNA integration and excision. Mol. Biotechnol. 19: 1-12
  8. Baneyx, F. 1999. Recombinant protein expression in Escherichia coli. Curr. Opin. Biotechnol. 10: 411-421
  9. Baneyx, F. and G. Georgiou. 1991. Construction and characterization of Escherichia coli strains deficient in multiple secreted proteases: Protease III degrades highmolecular- weight substrates in vivo. J. Bacteriol. 173: 2696-2703
  10. Barth, S., M. Huhn, B. Matthey, A. Klimka, E. A. Galinski, and A. Engert. 2000. Compatible-solute-supported periplasmic expression of functional recombinant proteins under stress conditions. Appl. Environ. Microbiol. 66: 1572-1579
  11. Batisson, I. and M. der Vartanian. 2000. Extracellular DsbA-insensitive folding of Escherichia coli heat-stable enterotoxin STa in vitro. J. Biol. Chem. 275: 10582-10589
  12. Bayer, M., R. Iberer, K. Bischof, E. Rassi, E. Stabentheiner, G. Zellnig, and G. Koraimann. 2001. Functional and mutational analysis of p19, a DNA transfer protein with muramidase activity. J. Bacteriol. 183: 3176-3183
  13. Belagaje, R. M., S. G. Reams, S. C. Ly, and W. F. Prouty. 1997. Increased production of low molecular weight recombinant proteins in Escherichia coli. Protein Sci. 6: 1953-1962
  14. Berg, O. G. and C. G. Kurland. 1997. Growth rate-optimised tRNA abundance and codon usage. J. Mol. Biol. 270: 544- 550
  15. Bessette, P. H., F. Aslund, J. Beckwith, and G. Georgiou. 1999. Efficient folding of proteins with multiple disulfide bonds in the Escherichia coli cytoplasm. Proc. Natl. Acad. Sci. USA 96: 13703-13708
  16. Binet, R., S. Letoffe, J. M. Ghigo, P. Delepelaire, and C. Wandersman. 1997. Protein secretion by Gram-negative bacterial ABC exporters - a review. Gene 192: 7-11
  17. Bonekamp, F., H. Dalboge, T. Christensen, and K. F. Jensen. 1989. Translation rates of individual codons are not correlated with tRNA abundances or with frequencies of utilization in Escherichia coli. J. Bacteriol. 171: 5812- 5816
  18. Bonekamp, F. and K. F. Jensen. 1988. The AGG codon is translated slowly in E. coli even at very low expression levels. Nucleic Acids Res. 16: 3013-3024
  19. Bostrom, M. and G. Larsson. 2002. Introduction of the carbohydrate-activated promoter P(malK) for recombinant protein production. Appl. Microbiol. Biotechnol. 59: 231- 238
  20. Bothmann, H. and A. Pluckthun. 2000. The periplasmic Escherichia coli peptidylprolyl cis,trans-isomerase FkpA. I. Increased functional expression of antibody fragments with and without cis-prolines. J. Biol. Chem. 275: 17100-17105
  21. Brendel, V., P. Bucher, I. R. Nourbakhsh, B. E. Blaisdell, and S. Karlin. 1992. Methods and algorithms for statistical analysis of protein sequences. Proc. Natl. Acad. Sci. USA 89: 2002-2006
  22. Burgess, R. R. and N. E. Thompson. 2002. Advances in gentle immunoaffinity chromatography. Curr. Opin. Biotechnol. 13: 304-308
  23. Canals, A., M. Ribo, A. Benito, M. Bosch, E. Mombelli, and M. Vilanova. 1999. Production of engineered human pancreatic ribonucleases, solving expression and purification problems, and enhancing thermostability. Protein Expr. Purif. 17: 169-181
  24. Carrier, T., K. L. Jones, and J. D. Keasling. 1998. mRNA stability and plasmid copy number effects on gene expression from an inducible promoter system. Biotechnol. Bioeng. 59: 666-672
  25. Cebolla, A., J. L. Royo, V. De Lorenzo, and E. Santero. 2002. Improvement of recombinant protein yield by a combination of transcriptional amplification and stabilization of gene expression. Appl. Environ. Microbiol. 68: 5034- 5041
  26. Chang, J. R., J. J. Choi, H. K. Kim, and S. T. Kwon. 2001. Purification and properties of Aquifex aeolicus DNA polymerase expressed in Escherichia coli. FEMS Microbiol. Lett. 201: 73-77
  27. Chang, S. G., D. Y. Kim, K. D. Choi, J. M. Shin, and H. C. Shin. 1998. Human insulin production from a novel mini-proinsulin which has high receptor-binding activity. Biochem. J. 329: 631-635
  28. Chatwin, H. M. and D. K. Summers. 2001. Monomer-dimer control of the ColE1 P(cer) promoter. Microbiol. 147: 3071- 3081
  29. Chen, G. F. and M. Inouye. 1990. Suppression of the negative effect of minor arginine codons on gene expression; preferential usage of minor codons within the first 25 codons of the Escherichia coli genes. Nucleic Acids Res. 18: 1465- 1473
  30. Chenal, A., P. Nizard, V. Forge, M. Pugniere, M. O. Roy, J. C. Mani, F. Guillain, and D. Gillet. 2002. Does fusion of domains from unrelated proteins affect their folding pathways and the structural changes involved in their function? A case study with the diphtheria toxin T domain. Protein Eng. 15: 383-391
  31. Choe, W. S., R. H. Clemmitt, H. A. Chase, and A. P. Middelberg. 2002. Comparison of histidine-tag capture chemistries for purification following chemical extraction. J. Chromatogr. A. 953: 111-121
  32. Choi, J., K. Ra, and Y. Lee. 1999. Enhancement of bovine growth hormone gene expression by increasing the plasmid copy number. Biotechnol. Lett. 21: 1-5
  33. Clark, E. D. 2001. Protein refolding for industrial processes. Curr. Opin. Biotechnol. 12: 202-207 https://doi.org/10.1016/S0958-1669(00)00200-7
  34. Cooper, K. W. and F. Baneyx. 2001. Escherichia coli FtsH (HflB) degrades a membrane-associated TolAI-II-betalactamase fusion protein under highly denaturing conditions. Protein Expr. Purif. 21: 323-332
  35. Cornelis, P. 2000. Expressing genes in different Escherichia coli compartments. Curr. Opin. Biotechnol. 11: 450-454
  36. Cornelis, P., J. C. Sierra, A. Lim, Jr., A. Malur, S. Tungpradabkul, H. Tazka, A. Leitao, C. V. Martins, C. di Perna, L. Brys, P. De Baetseller, and R. Hamers. 1996. Development of new cloning vectors for the production of immunogenic outer membrane fusion proteins in Escherichia coli. Biotechnol. (N Y). 14: 203-208 https://doi.org/10.1038/nbt0296-203
  37. Cranenburgh, R. M., J. A. Hanak, S. G. Williams, and D. J. Sherratt. 2001. Escherichia coli strains that allow antibioticfree plasmid selection and maintenance by repressor titration. Nucleic Acids Res. 29: E26
  38. Cubarsi, R., M. M. Carrio, and A. Villaverde. 2001. In situ proteolytic digestion of inclusion body polypeptides occurs as a cascade process. Biochem. Biophys. Res. Commun. 282: 436-441
  39. del Solar, G., R. Giraldo, M. J. Ruiz-Echevarria, M. Espinosa, and R. Diaz-Orejas. 1998. Replication and control of circular bacterial plasmids. Microbiol. Mol. Biol. Rev. 62: 434-464
  40. del Tito, B. J., Jr., J. M. Ward, J. Hodgson, C. J. Gershater, H. Edwards, L. A. Wysocki, F. A. Watson, G. Sathe, and J. F. Kane. 1995. Effects of a minor isoleucyl tRNA on heterologous protein translation in Escherichia coli. J. Bacteriol. 177: 7086-7091
  41. Dias, A. 1990. Overproduction of proteins in Escherichia coli: Vectors, hosts and strategies. Methods Enzymol. 182: 93-112 https://doi.org/10.1016/0076-6879(90)82011-P
  42. Dong, H., L. Nilsson, and C. G. Kurland. 1995. Gratuitous overexpression of genes in Escherichia coli leads to growth inhibition and ribosome destruction. J. Bacteriol. 177: 1497-1504
  43. Dong, H., L. Nilsson, and C. G. Kurland. 1996. Co-variation of tRNA abundance and codon usage in Escherichia coli at different growth rates. J. Mol. Biol. 260: 649-663 https://doi.org/10.1006/jmbi.1996.0428
  44. Economou, A. 1999. Following the leader: Bacterial protein export through the Sec pathway. Trends Microbiol. 7: 315- 320
  45. Estrem, S. T., T. Gaal, W. Ross, and R. L. Gourse. 1998. Identification of an UP element consensus sequence for bacterial promoters. Proc. Natl. Acad. Sci. USA 95: 9761-9766
  46. Fargo, D. C., J. E. Boynton, and N. W. Gillham. 1999. Mutations altering the predicted secondary structure of a chloroplast 5' untranslated region affect its physical and biochemical properties as well as its ability to promote translation of reporter mRNAs both in the Chlamydomonas reinhardtii chloroplast and in Escherichia coli. Mol. Cell. Biol. 19: 6980-6990
  47. Fernandez, L. A. and V. de Lorenzo. 2001. Formation of disulphide bonds during secretion of proteins through the periplasmic-independent type I pathway. Mol. Microbiol. 40: 332-346 https://doi.org/10.1046/j.1365-2958.2001.02410.x
  48. Fernandez, L. A., I. Sola, L. Enjuanes, and V. de Lorenzo. 2000. Specific secretion of active single-chain Fv antibodies into the supernatants of Escherichia coli cultures by use of the hemolysin system. Appl. Environ. Microbiol. 66: 5024- 5029
  49. Gautam, A. and D. Bastia. 2001. A replication terminus located at or near a replication checkpoint of Bacillus subtilis functions independently of stringent control. J. Biol. Chem. 276: 8771-8777
  50. Gavit, P. and M. Better. 2000. Production of antifungal recombinant peptides in Escherichia coli. J. Biotechnol. 79: 127-136
  51. Goldman, E., A. H. Rosenberg, G. Zubay, and F. W. Studier. 1995. Consecutive low-usage leucine codons block translation only when near the 5$^'$ end of a message in Escherichia coli. J. Mol. Biol. 245: 467-473
  52. Gottesman, M. E. and W. A. Hendrickson. 2000. Protein folding and unfolding by Escherichia coli chaperones and chaperonins. Curr. Opin. Microbiol. 3: 197-202
  53. Gottesman, S. 1996. Proteases and their targets in Escherichia coli. Annu. Rev. Genet. 30: 465-506
  54. Grosjean, H. and W. Fiers. 1982. Preferential codon usage in prokaryotic genes: The optimal codon-anticodon interaction energy and the selective codon usage in efficiently expressed genes. Gene 18: 199-209
  55. Grossman, T. H., E. S. Kawasaki, S. R. Punreddy, and M. S. Osburne. 1998. Spontaneous cAMP-dependent derepression of gene expression in stationary phase plays a role in recombinant expression instability. Gene 209: 95-103
  56. Guarente, L., G. Lauer, T. M. Roberts, and M. Ptashne. 1980. Improved methods for maximizing expression of a cloned gene: A bacterium that synthesizes rabbit betaglobin. Cell 20: 543-553
  57. Guisez, Y., I. Fache, L. A. Campfield, F. J. Smith, A. Farid, G. Plaetinck, J. Van der Heyden, J. Tavernier, W. Fiers, P. Burn, and R. Devos. 1998. Efficient secretion of biologically active recombinant OB protein (leptin) in Escherichia coli, purification from the periplasm and characterization. Protein Expr. Purif. 12: 249-258
  58. Guisez, Y., J. Robbens, E. Remaut, and W. Fiers. 1993. Folding of the MS2 coat protein in Escherichia coli is modulated by translational pauses resulting from mRNA secondary structure and codon usage: a hypothesis. J. Theor. Biol. 162: 243-252
  59. Hamilton, S. R., J. B. O’Donnell, Jr., A. Hammet, D. Stapleton, S. A. Habinowski, A. R. Means, B. E. Kemp, and L. A. Witters. 2002. AMP-activated protein kinase kinase: Detection with recombinant AMPK alpha1 subunit. Biochem. Biophys. Res. Commun. 293: 892-898
  60. Hammarberg, B., P. A. Nygren, E. Holmgren, A. Elmblad, M. Tally, U. Hellman, T. Moks, and M. Uhlen. 1989. Dual affinity fusion approach and its use to express recombinant human insulin-like growth factor II. Proc. Natl. Acad. Sci. USA 86: 4367-4371
  61. Han, S. J., H. N. Chang, and J. Lee. 2001. Characterization of an oxygen-dependent inducible promoter, the nar promoter of Escherichia coli, to utilize in metabolic engineering. Biotechnol. Bioeng. 72: 573-576
  62. Hannig, G. and S. C. Makrides. 1998. Strategies for optimizing heterologous protein expression in Escherichia coli. Trends Biotechnol. 16: 54-60
  63. Hasenwinkle, D., E. Jervis, O. Kops, C. Liu, G. Lesnicki, C. Haynes, and D. Kilburn. 1997. Very high-level production and export in Escherichia coli of a cellulose binding domain for use in a generic secretion-affinity fusion system. Biotechnol. Bioeng. 55: 854-863
  64. Hellebust, H., M. Murby, L. Abrahmsen, M. Uhlen, and S. Enfors. 1989. Different approaches to stabilize a recombinant fusion protein. Bio/Technology 7: 165-168
  65. Herman-Antosiewicz, A., M. Obuchowski, and G. Wegrzyn. 2001. A plasmid cloning vector with precisely regulatable copy number in Escherichia coli. Mol. Biotechnol. 17: 193- 199
  66. Hernan, R. A., H. L. Hui, M. E. Andracki, R. W. Noble, S. G. Sligar, J. A. Walder, and R. Y. Walder. 1992. Human hemoglobin expression in Escherichia coli: Importance of optimal codon usage. Biochem. 31: 8619-8628
  67. Hew, Y., C. Lau, Z. Grzelczak, and F. W. Keeley. 2000. Identification of a GA-rich sequence as a proteinbinding site in the 3$^'$-untranslated region of chicken elastin mRNA with a potential role in the developmental regulation of elastin mRNA stability. J. Biol. Chem. 275: 24857- 24864
  68. Holm, L. 1986. Codon usage and gene expression. Nucleic Acids Res. 14: 3075-3087
  69. Honey, S., B. L. Schneider, D. M. Schieltz, J. R. Yates, and B. Futcher. 2001. A novel multiple affinity purification tag and its use in identification of proteins associated with a cyclin-CDK complex. Nucleic Acids Res. 29: E24
  70. Huang, H. C., M. Y. Sherman, O. Kandror, and A. L. Goldberg. 2001. The molecular chaperone DnaJ is required for the degradation of a soluble abnormal protein in Escherichia coli. J. Biol. Chem. 276: 3920-3928
  71. Ignatova, Z., A. Mahsunah, M. Georgieva, and V. Kasche. 2003. Improvement of posttranslational bottlenecks in the production of penicillin amidase in recombinant Escherichia coli strains. Appl. Environ. Microbiol. 69: 1237-1245
  72. Ikemura, T. 1981. Correlation between the abundance of Escherichia coli transfer RNAs and the occurrence of the respective codons in its protein genes. J. Mol. Biol. 146: 1- 21
  73. Ikemura, T. 1981. Correlation between the abundance of Escherichia coli transfer RNAs and the occurrence of the respective codons in its protein genes: A proposal for a synonymous codon choice that is optimal for the E. coli translational system. J. Mol. Biol. 151: 389-409
  74. Jeong, K. J. and S. Y. Lee. 2001. Secretory production of human granulocyte colony-stimulating factor in Escherichia coli. Protein Expr. Purif. 23: 311-318
  75. Jeong, K. J. and S. Y. Lee. 2002. Excretion of human betaendorphin into culture medium by using outer membrane protein F as a fusion partner in recombinant Escherichia coli. Appl. Environ. Microbiol. 68: 4979-4985
  76. Jeong, K. J. and S. Y. Lee. 2003. Enhanced production of recombinant proteins in Escherichia coli by filamentation suppression. Appl. Environ. Microbiol. 69: 1295-1298
  77. Joly, J. C., W. S. Leung, and J. R. Swartz. 1998. Overexpression of Escherichia coli oxidoreductases increases recombinant insulin-like growth factor-I accumulation. Proc. Natl. Acad. Sci. USA 95: 2773-2777
  78. Jonasson, P., J. Nilsson, E. Samuelsson, T. Moks, S. Stahl, and M. Uhlen. 1996. Single-step trypsin cleavage of a fusion protein to obtain human insulin and its C peptide. Eur. J. Biochem. 236: 656-661
  79. Jordi, B. J., T. A. Owen-Hughes, C. S. Hulton, and C. F. Higgins. 1995. DNA twist, flexibility and transcription of the osmoregulated proU promoter of Salmonella typhimurium. EMBO J. 14: 5690-5700
  80. Kajava, A. V., S. N. Zolov, A. E. Kalinin, and M. A. Nesmeyanova. 2000. The net charge of the first 18 residues of the mature sequence affects protein translocation across the cytoplasmic membrane of gram-negative bacteria. J. Bacteriol. 182: 2163-2169
  81. Kane, J. F. 1995. Effects of rare codon clusters on high-level expression of heterologous proteins in Escherichia coli. Curr. Opin. Biotechnol. 6: 494-500 https://doi.org/10.1016/0958-1669(95)80082-4
  82. Kang, Y. and J. W. Yoon. 1994. Effect of modification of connecting peptide of proinsulin on its export. J. Biotechnol. 36: 45-54
  83. Keefe, A. D., D. S. Wilson, B. Seelig, and J. W. Szostak. 2001. One-step purification of recombinant proteins using a nanomolar-affinity streptavidin-binding peptide, the SBPTag. Protein Expr. Purif. 23: 440-446
  84. Kelley, B. D. 2001. Biochemical engineering: Bioprocessing of therapeutic proteins. Curr. Opin. Biotechnol. 12: 173- 174 https://doi.org/10.1016/S0958-1669(00)00195-6
  85. Kim, B. G. 1990. Analysis of pBR322 replication kinetics and its dependency on growth rate. Biotechnol. Bioeng. 36: 233-242 https://doi.org/10.1002/bit.260360304
  86. Kim, J., J. Luirink, and D. A. Kendall. 2000. SecB dependence of an exported protein is a continuum influenced by the characteristics of the signal peptide or early mature region. J. Bacteriol. 182: 4108-4112
  87. Kim, Y. S., H. C. Jung, and J. G. Pan. 2000. Bacterial cell surface display of an enzyme library for selective screening of improved cellulase variants. Appl. Environ. Microbiol. 66: 788-793
  88. Kitagawa, J., K. Yamamoto, and H. Iba. 2001. Computational analysis of sos response in ultraviolet-irradiated Escherichia coli. Genome Inf. 12: 280-281
  89. Koster, M., W. Bitter, and J. Tommassen. 2000. Protein secretion mechanisms in Gram-negative bacteria. Int. J. Med. Microbiol. 290: 325-331
  90. Kurokawa, Y., H. Yanagi, and T. Yura. 2000. Overexpression of protein disulfide isomerase DsbC stabilizes multipledisulfide- bonded recombinant protein produced and transported to the periplasm in Escherichia coli. Appl. Environ. Microbiol. 66: 3960-3965
  91. Kweon, D. H., D. H. Lee, N. S. Han, C. S. Rha, and J. H. Seo. 2002. Characterization of polycationic amino acids fusion systems for ion-exchange purification of cyclodextrin glycosyltransferase from recombinant Escherichia coli. Biotechnol. Prog. 18: 303-308
  92. Lai, W. B. and A. P. Middelberg. 2002. The production of human papillomavirus type 16 L1 vaccine product from Escherichia coli inclusion bodies. Bioprocess Biosyst. Eng. 25: 121-128
  93. Lederberg, J. 1998. Plasmid (1952-1997). Plasmid 39: 1-9
  94. Lee, J., M. Cho, E. Hong, K. Kim, and J. Lee. 1996. Characterization of the nar promoter to use as an inducible promoter. Biotechnol. Lett. 18: 129-134
  95. Lee, S., I. Kim, D. Kim, K. Bae, and S. Byun. 1998. High level secretion of recombinant staphylokinase into periplasm of Escherichia coli. Biotechnol. Lett. 20: 113-116
  96. Lee, S. B. and J. E. Bailey. 2000. Analysis of growth rate effects on productivity of recombinant Escherichia coli populations using molecular mechanism models. Biotechnol. Bioeng. 26: 66-73
  97. Lee, S. Y. 1996. High cell-density culture of Escherichia coli. Trends Biotechnol. 14: 98-105 https://doi.org/10.1016/0167-7799(96)80930-9
  98. Lellouch, A. C. and R. A. Geremia. 1999. Expression and study of recombinant ExoM, a beta1-4 glucosyltransferase involved in succinoglycan biosynthesis in Sinorhizobium meliloti. J. Bacteriol. 181: 1141-1148
  99. Levine, A. D., S. H. Rangwala, N. A. Horn, M. A. Peel, B. K. Matthews, R. M. Leimgruber, J. A. Manning, B. F. Bishop, and P. O. Olins. 1995. High level expression and refolding of mouse interleukin 4 synthesized in Escherichia coli. J. Biol. Chem. 270: 7445-7452
  100. Loo, T., M. L. Patchett, G. E. Norris, and J. S. Lott. 2002. Using secretion to solve a solubility problem: High-yield expression in Escherichia coli and purification of the bacterial glycoamidase PNGase F. Protein Expr. Purif. 24: 90-98
  101. Mackin, R. B. 1999. Streamlined procedure for the production of normal and altered versions of recombinant human proinsulin. Protein Expr. Purif. 15: 308-313 https://doi.org/10.1006/prep.1998.1024
  102. Makoff, A. J., M. D. Oxer, M. A. Romanos, N. F. Fairweather, and S. Ballantine. 1989. Expression of tetanus toxin fragment C in E. coli: high level expression by removing rare codons. Nucleic Acids Res. 17: 10191- 10202
  103. Makrides, S. C. 1996. Strategies for achieving high-level expression of genes in Escherichia coli. Microbiol. Rev. 60: 512-538
  104. Manosroi, J., C. Tayapiwatana, F. Gotz, R. G. Werner, and A. Manosroi. 2001. Secretion of active recombinant human tissue plasminogen activator derivatives in Escherichia coli. Appl. Environ. Microbiol. 67: 2657-2664
  105. McKern, N. M., M. Lou, M. J. Frenkel, A. Verkuylen, J. D. Bentley, G. O. Lovrecz, N. Ivancic, T. C. Elleman, T. P. Garrett, L. J. Cosgrove, and C. W. Ward. 1997. Crystallization of the first three domains of the human insulin-like growth factor-1 receptor. Protein Sci. 6: 2663- 2666
  106. Meerman, H. J. and G. Georgiou. 1994. Construction and characterization of a set of E. coli strains deficient in all known loci affecting the proteolytic stability of secreted recombinant proteins. Biotechnol. (N Y). 12: 1107-1110
  107. Mellies, J., R. Brems, and M. Villarejo. 1994. The Escherichia coli proU promoter element and its contribution to osmotically signaled transcription activation. J. Bacteriol. 176: 3638-3645
  108. Mergulhão, F., G. Monteiro, A. Kelly, M. Taipa, and J. Cabral. 2000. Recombinant human proinsulin: A new approach in gene assembly and protein expression. J. Microbiol. Biotechnol. 10: 690-693
  109. Mergulhão, F., G. Monteiro, G. Larsson, A. Sandem, A. Farewell, T. Nystrom, J. Cabral, and M. Taipa. 2003. Medium and copy number effects on the secretion of human proinsulin in Escherichia coli using the universal stress promoters uspA and uspB. Appl. Microbiol. Biotechnol. 61: 495-501
  110. Mergulhão, F. J., G. A. Monteiro, J. M. Cabral, and M. A. Taipa. 2001. A quantitative ELISA for monitoring the secretion of ZZ-fusion proteins using SpA domain as immunodetection reporter system. Mol. Biotechnol. 19: 239-244
  111. Mergulhão, F. J. M., G. A. Monteiro, G. Larsson, M. Bostrom, A. Farewell, T. Nystrom, J. M. S. Cabral, and M. A. Taipa. 2003. Evaluation of inducible promoters on the secretion of a ZZ-Proinsulin fusion protein. Biotechnol. Appl. Biochem. 38: 87-93
  112. Middelberg, A. 2002. Preparative protein refolding. Trends Biotechnol. 20: 437
  113. Mikhaleva, N. I., V. V. Golovastov, S. N. Zolov, M. V. Bogdanov, W. Dowhan, and M. A. Nesmeyanova. 2001. Depletion of phosphatidylethanolamine affects secretion of Escherichia coli alkaline phosphatase and its transcriptional expression. FEBS Lett. 493: 85-90
  114. Misoka, F., T. Miyake, K. Miyoshi, M. Sugiyama, S. Sakamoto, and T. Fuwa. 1989. Overproduction of human insulin-like growth factor-II in Escherichia coli. Biotechnol. Lett. 11: 839-844
  115. Missiakas, D. and S. Raina. 1997. Protein misfolding in the cell envelope of Escherichia coli: New signaling pathways. Trends Biochem. Sci. 22: 59-63
  116. Moks, T., L. Abrahmsen, E. Holmgren, M. Bilich, A. Olsson, M. Uhlen, G. Pohl, C. Sterky, H. Hultberg, S. Josephson, et al. 1987. Expression of human insulin-like growth factor I in bacteria: use of optimized gene fusion vectors to facilitate protein purification. Biochem. 26: 5239-5244
  117. Monzavi-Karbassi, B., G. Cunto-Amesty, P. Luo, and T. Kieber-Emmons. 2002. Peptide mimotopes as surrogate antigens of carbohydrates in vaccine discovery. Trends Biotechnol. 20: 207-214
  118. Mujacic, M., K. W. Cooper, and F. Baneyx. 1999. Coldinducible cloning vectors for low-temperature protein expression in Escherichia coli: Application to the production of a toxic and proteolytically sensitive fusion protein. Gene 238: 325-332
  119. Murby, M., P. A. Nygren, H. Rondahl, U. Hellman, S. O. Enfors, and M. Uhlen. 1991. Differential degradation of a recombinant albumin-binding receptor in Escherichia coli. Eur. J. Biochem. 199: 41-46
  120. Murby, M., E. Samuelsson, T. N. Nguyen, L. Mignard, U. Power, H. Binz, M. Uhlen, and S. Stahl. 1995. Hydrophobicity engineering to increase solubility and stability of a recombinant protein from respiratory syncytial virus. Eur. J. Biochem. 230: 38-44
  121. Nakai, K. and M. Kanehisa. 1991. Expert system for predicting protein localization sites in gram-negative bacteria. Proteins 11: 95-110
  122. Nakamura, Y. and K. Ito. 2002. A tripeptide discriminator for stop codon recognition. FEBS Lett. 514: 30-33
  123. Netzer, W. J. and F. U. Hartl. 1998. Protein folding in the cytosol: Chaperonin-dependent and -independent mechanisms. Trends Biochem. Sci. 23: 68-73
  124. Nielsen, H., J. Engelbrecht, S. Brunak, and G. von Heijne. 1997. Identification of prokaryotic and eukaryotic signal peptides and prediction of their cleavage sites. Protein Eng. 10: 1-6
  125. Nielsen, P. E. 1999. Applications of peptide nucleic acids. Curr. Opin. Biotechnol. 10: 71-75 https://doi.org/10.1016/S0958-1669(99)80013-5
  126. Nilsson, B. and L. Abrahmsen. 1990. Fusions to staphylococcal protein A. Methods Enzymol. 185: 144-161
  127. Nilsson, B., G. Forsberg, T. Moks, M. Hartmanis, and M. Uhlen. 1992. Fusion proteins in biotechnology. Curr. Opin. Biotechnol. 3: 363-369
  128. Nilsson, J., S. Stahl, J. Lundeberg, M. Uhlen, and P. A. Nygren. 1997. Affinity fusion strategies for detection, purification, and immobilization of recombinant proteins. Protein Expr. Purif. 11: 1-16
  129. Nishihara, K., M. Kanemori, M. Kitagawa, H. Yanagi, and T. Yura. 1998. Chaperone coexpression plasmids: Differential and synergistic roles of DnaK-DnaJ-GrpE and GroEL-GroES in assisting folding of an allergen of Japanese cedar pollen, Cryj2, in Escherichia coli. Appl. Environ. Microbiol. 64: 1694-1699
  130. Nygren, P. A., S. Stahl, and M. Uhlen. 1994. Engineering proteins to facilitate bioprocessing. Trends Biotechnol. 12: 184-188
  131. Palacios, J. L., I. Zaror, P. Martinez, F. Uribe, P. Opazo, T. Socias, M. Gidekel, and A. Venegas. 2001. Subset of hybrid eukaryotic proteins is exported by the type I secretion system of Erwinia chrysanthemi. J. Bacteriol. 183: 1346- 1358
  132. Panayotatos, N. and K. Truong. 1985. Cleavage within an RNase III site can control mRNA stability and protein synthesis in vivo. Nucleic Acids Res. 13: 2227-2240
  133. Pines, O. and M. Inouye. 1999. Expression and secretion of proteins in E. coli. Mol. Biotechnol. 12: 25-34
  134. Polyak, S. W., G. Forsberg, B. E. Forbes, K. A. McNeil, S. E. Aplin, and J. C. Wallace. 1997. Introduction of spacer peptides N-terminal to a cleavage recognition motif in recombinant fusion proteins can improve site-specific cleavage. Protein Eng. 10: 615-619
  135. Prinz, W. A., F. Aslund, A. Holmgren, and J. Beckwith. 1997. The role of the thioredoxin and glutaredoxin pathways in reducing protein disulfide bonds in the Escherichia coli cytoplasm. J. Biol. Chem. 272: 15661-15667
  136. Prytz, I., A. M. Sandén, T. Nystrom, A. Farewell, A. Wahlstrom, C. Forberg, I. Tubulekas, Z. Pragai, M. Barer, C. Harwood, and G. Larsson. 2002. Fed-batch production of recombinant beta-galactosidase using the universal stress promoters uspA and uspB in high cell density cultivation. Biotechnol. Bioeng. 83: 595-603
  137. Pugsley, A. P. 1993. The complete general secretory pathway in gram-negative bacteria. Microbiol. Rev. 57: 50- 108
  138. Pugsley, A. P., O. Francetic, O. M. Possot, N. Sauvonnet, and K. Hardie. 1997. Recent progress and future directions in studies of the main terminal branch of the general secretory pathway in Gram-neagtive bacteria - a review. Gene 192: 13-19 https://doi.org/10.1016/S0378-1119(96)00803-7
  139. Puri, N., K. B. Appa Rao, S. Menon, A. K. Panda, G. Tiwari, L. C. Garg, and S. M. Totey. 1999. Effect of the codon following the ATG start site on the expression of ovine growth hormone in Escherichia coli. Protein Expr. Purif. 17: 215-223
  140. Qiu, J., J. R. Swartz, and G. Georgiou. 1998. Expression of active human tissue-type plasminogen activator in Escherichia coli. Appl. Environ. Microbiol. 64: 4891- 4896
  141. Rinas, U. and J. Bailey. 1992. Protein compositional analysis of inclusion bodies produced in recombinant Escherichia coli. Appl. Microbiol. Biotechnol. 37: 609-614
  142. Robinson, M., R. Lilley, S. Little, J. S. Emtage, G. Yarranton, P. Stephens, A. Millican, M. Eaton, and G. Humphreys. 1984. Codon usage can affect efficiency of translation of genes in Escherichia coli. Nucleic Acids Res. 12: 6663-6671
  143. Rosenbaum, V., T. Klahn, U. Lundberg, E. Holmgren, A. von Gabain, and D. Riesner. 1993. Co-existing structures of an mRNA stability determinant. The 5' region of the Escherichia coli and Serratia marcescens ompA mRNA. J. Mol. Biol. 229: 656-670
  144. Rosenberg, A. H., E. Goldman, J. J. Dunn, F. W. Studier, and G. Zubay. 1993. Effects of consecutive AGG codons on translation in Escherichia coli, demonstrated with a versatile codon test system. J. Bacteriol. 175: 716-722
  145. Rosenberg, H. F. 1998. Isolation of recombinant secretory proteins by limited induction and quantitative harvest. Biotechniques 24: 188-191
  146. Ross, W., S. E. Aiyar, J. Salomon, and R. L. Gourse. 1998. Escherichia coli promoters with UP elements of different strengths: Modular structure of bacterial promoters. J. Bacteriol. 180: 5375-5383
  147. Rowe, D. C. and D. K. Summers. 1999. The quiescent-cell expression system for protein synthesis in Escherichia coli. Appl. Environ. Microbiol. 65: 2710-2715
  148. Salmond, G. P. and P. J. Reeves. 1993. Membrane traffic wardens and protein secretion in gram-negative bacteria. Trends Biochem. Sci. 18: 7-12
  149. Samuelsson, E., P. Jonasson, F. Viklund, B. Nilsson, and M. Uhlen. 1996. Affinity-assisted in vivo folding of a secreted human peptide hormone in Escherichia coli. Nat. Biotechnol. 14: 751-755
  150. Sandkvist, M. 2001. Biology of type II secretion. Mol. Microbiol. 40: 271-283
  151. Sauvonnet, N., I. Poquet, and A. P. Pugsley. 1995. Extracellular secretion of pullulanase is unaffected by minor sequence changes but is usually prevented by adding reporter proteins to its N- or C-terminal end. J. Bacteriol. 177: 5238-5246
  152. Sawers, G. and M. Jarsch. 1996. Alternative regulation principles for the production of recombinant proteins in Escherichia coli. Appl. Microbiol. Biotechnol. 46: 1-9
  153. Schaffner, J., J. Winter, R. Rudolph, and E. Schwarz. 2001. Cosecretion of chaperones and low-molecular-size medium additives increases the yield of recombinant disulfidebridged proteins. Appl. Environ. Microbiol. 67: 3994- 4000
  154. Schenborn, E. and D. Groskreutz. 1999. Reporter gene vectors and assays. Mol. Biotechnol. 13: 29-44
  155. Schmidt, M., E. Viaplana, F. Hoffmann, S. Marten, A. Villaverde, and U. Rinas. 1999. Secretion-dependent proteolysis of heterologous protein by recombinant Escherichia coli is connected to an increased activity of the energy-generating dissimilatory pathway. Biotechnol. Bioeng. 66: 61-67
  156. Seffens, W. and D. Digby. 1999. mRNAs have greater negative folding free energies than shuffled or codon choice randomized sequences. Nucleic Acids Res. 27: 1578-1584
  157. Serra, E. C., N. Carrillo, A. R. Krapp, and E. A. Ceccarelli. 1993. One-step purification of plant ferredoxin-NADP+ oxidoreductase expressed in Escherichia coli as fusion with glutathione S-transferase. Protein Expr. Purif. 4: 539-546
  158. Sharpe, M. E., H. M. Chatwin, C. Macpherson, H. L. Withers, and D. K. Summers. 1999. Analysis of the CoIE1 stability determinant Rcd. Microbiol. 145: 2135-2144
  159. Shokri, A., A. M. Sanden, and G. Larsson. 2002. Growth rate-dependent changes in Escherichia coli membrane structure and protein leakage. Appl. Microbiol. Biotechnol. 58: 386-392
  160. Shokri, A., A. M. Sandén, and G. Larsson. 2003. Cell and process design for targeting of recombinant protein into the culture medium of Escherichia coli. Appl. Microbiol. Biotechnol. 60: 654-664
  161. Siegele, D. A. and J. C. Hu. 1997. Gene expression from plasmids containing the araBAD promoter at subsaturating inducer concentrations represents mixed populations. Proc. Natl. Acad. Sci. USA 94: 8168-8172
  162. Simmons, L. C. and D. G. Yansura. 1996. Translational level is a critical factor for the secretion of heterologous proteins in Escherichia coli. Nat. Biotechnol. 14: 629-634
  163. Smolke, C. D. and J. D. Keasling. 2002. Effect of copy number and mRNA processing and stabilization on transcript and protein levels from an engineered dual-gene operon. Biotechnol. Bioeng. 78: 412-424
  164. Sozhamannan, S. and B. L. Stitt. 1997. Effects on mRNA degradation by Escherichia coli transcription termination factor Rho and pBR322 copy number control protein Rop. J. Mol. Biol. 268: 689-703
  165. Spanjaard, R. A. and J. van Duin. 1988. Translation of the sequence AGG-AGG yields 50% ribosomal frameshift. Proc. Natl. Acad. Sci. USA 85: 7967-7971 https://doi.org/10.1073/pnas.85.21.7967
  166. Stacey, S. N., D. Jordan, A. J. Williamson, M. Brown, J. H. Coote, and J. R. Arrand. 2000. Leaky scanning is the predominant mechanism for translation of human papillomavirus type 16 E7 oncoprotein from E6/E7 bicistronic mRNA. J. Virol. 74: 7284-7297
  167. Stader, J. A. and T. J. Silhavy. 1990. Engineering Escherichia coli to secrete heterologous gene products. Methods Enzymol. 185: 166-187
  168. Stahl, S., J. Nilsson, S. Hober, M. Uhlen, and P. Nygren. 1999. Affinity fusions, gene expression, pp. 49-63. In M. Flickinger and Drew S. (eds.), Encyclopedia of Bioprocess Technology: Fermentation, Biocatalysis and Bioseparation. John Wiley & Sons, New York, U.S.A
  169. Stahl, S. and P. A. Nygren. 1997. The use of gene fusions to protein A and protein G in immunology and biotechnology. Pathol. Biol. (Paris) 45: 66-76
  170. Stahl, S. and M. Uhlen. 1997. Bacterial surface display: Trends and progress. Trends Biotechnol. 15: 185-192
  171. Su, X., A. K. Prestwood, and R. A. McGraw. 1992. Production of recombinant porcine tumor necrosis factor alpha in a novel E. coli expression system. Biotechniques 13: 756-762
  172. Summers, D. 1998. Timing, self-control and a sense of direction are the secrets of multicopy plasmid stability. Mol. Microbiol. 29: 1137-1145
  173. Summers, R. G., C. R. Harris, and J. R. Knowles. 1989. A conservative amino acid substitution, arginine for lysine, abolishes export of a hybrid protein in Escherichia coli. Implications for the mechanism of protein secretion. J. Biol. Chem. 264: 20082-20088
  174. Summers, R. G. and J. R. Knowles. 1989. Illicit secretion of a cytoplasmic protein into the periplasm of Escherichia coli requires a signal peptide plus a portion of the cognate secreted protein. Demarcation of the critical region of the mature protein. J. Biol. Chem. 264: 20074-20081
  175. Swamy, K. H. and A. L. Goldberg. 1982. Subcellular distribution of various proteases in Escherichia coli. J. Bacteriol. 149: 1027-1033
  176. Swartz, J. R. 2001. Advances in Escherichia coli production of therapeutic proteins. Curr. Opin. Biotechnol. 12: 195-201 https://doi.org/10.1016/S0958-1669(00)00199-3
  177. Szweda, P., R. Pladzyk, R. Kotlowski, and J. Kur. 2001. Cloning, expression, and purification of the Staphylococcus simulans lysostaphin using the intein-chitin-binding domain (CBD) system. Protein Expr. Purif. 22: 467-471
  178. Taguchi, S., K. I. Nishihama, K. Igi, K. Ito, H. Taira, M. Motoki, and H. Momose. 2000. Substrate specificity analysis of microbial transglutaminase using proteinaceous protease inhibitors as natural model substrates. J. Biochem. (Tokyo) 128: 415-425
  179. Talmadge, K. and W. Gilbert. 1982. Cellular location affects protein stability in Escherichia coli. Proc. Natl. Acad. Sci. USA 79: 1830-1833
  180. Tang, J. and M. Hu. 1993. Production of human proinsulin in E. coli in a non-fusion form. Biotechnol. Lett. 15: 661- 666
  181. Terpe, K. 2003. Overview of tag protein fusions: From molecular and biochemical fundamentals to commercial systems. Appl. Microbiol. Biotechnol. 60: 523-533
  182. Thomas, J. G. and F. Baneyx. 1996. Protein misfolding and inclusion body formation in recombinant Escherichia coli cells overexpressing heat-shock proteins. J. Biol. Chem. 271: 11141-11147
  183. Thomas, J. G. and F. Baneyx. 1997. Divergent effects of chaperone overexpression and ethanol supplementation on inclusion body formation in recombinant Escherichia coli. Protein Expr. Purif. 11: 289-296
  184. Thomas, J. G. and F. Baneyx. 2000. ClpB and HtpG facilitate de novo protein folding in stressed Escherichia coli cells. Mol. Microbiol. 36: 1360-1370
  185. Tomme, P., A. Boraston, B. McLean, J. Kormos, A. L. Creagh, K. Sturch, N. R. Gilkes, C. A. Haynes, R. A. Warren, and D. G. Kilburn. 1998. Characterization and affinity applications of cellulose-binding domains. J. Chromatogr. B. Biomed. Sci. Appl. 715: 283-296
  186. Tomoyasu, T., A. Mogk, H. Langen, P. Goloubinoff, and B. Bukau. 2001. Genetic dissection of the roles of chaperones and proteases in protein folding and degradation in the Escherichia coli cytosol. Mol. Microbiol. 40: 397-413
  187. Tsuji, A., H. Koshimoto, Y. Sato, M. Hirano, Y. Sei-Iida, S. Kondo, and K. Ishibashi. 2000. Direct observation of specific messenger RNA in a single living cell under a fluorescence microscope. Biophys. J. 78: 3260-3274
  188. Tunner, J. R. and C. R. Robertson. 1992. Use of glucose starvation to limit growth and induce protein production in Escherichia coli. Biotechnol. Bioeng. 40: 271-279
  189. Uhlen, M., T. Moks, and L. Abrahmsen. 1988. Protein engineering to optimize recombinant protein purification. Biochem. Soc. Trans. 16: 111-112
  190. Vasina, J. A. and F. Baneyx. 1997. Expression of aggregation-prone recombinant proteins at low temperatures: A comparative study of the Escherichia coli cspA and tac promoter systems. Protein Expr. Purif. 9: 211-218
  191. Vasina, J. A., M. S. Peterson, and F. Baneyx. 1998. Scaleup and optimization of the low-temperature inducible cspA promoter system. Biotechnol. Prog. 14: 714-721
  192. Wang, H., D. J. O’Mahony, D. J. McConnell, and S. Z. Qi. 1993. Optimization of the synthesis of porcine somatotropin in Escherichia coli. Appl. Microbiol. Biotechnol. 39: 324- 328
  193. Williams, D. P., D. Regier, D. Akiyoshi, F. Genbauffe, and J. R. Murphy. 1988. Design, synthesis and expression of a human interleukin-2 gene incorporating the codon usage bias found in highly expressed Escherichia coli genes. Nucleic Acids Res. 16: 10453-10467
  194. Winter, J., P. Neubauer, R. Glockshuber, and R. Rudolph. 2001. Increased production of human proinsulin in the periplasmic space of Escherichia coli by fusion to DsbA. J. Biotechnol. 84: 175-185
  195. Workman, C. and A. Krogh. 1999. No evidence that mRNAs have lower folding free energies than random sequences with the same dinucleotide distribution. Nucleic Acids Res. 27: 4816-4822
  196. Yokoyama, S. 2003. Protein expression systems for structural genomics and proteomics. Curr. Opin. Chem. Biol. 7: 39-43
  197. Yoon, S. and W. Kang. 1994. Fed-batch operation of recombinant Escherichia coli containing the trp promoter with controlled specific growth rate. Biotechnol. Bioeng. 43
  198. Zahn, K. 1996. Overexpression of an mRNA dependent on rare codons inhibits protein synthesis and cell growth. J. Bacteriol. 178: 2926-2933
  199. Zavialov, A. V., N. V. Batchikova, T. Korpela, L. E. Petrovskaya, V. G. Korobko, J. Kersley, S. MacIntyre, and V. P. Zav’yalov. 2001. Secretion of recombinant proteins via the chaperone/usher pathway in Escherichia coli. Appl. Environ. Microbiol. 67: 1805-1814
  200. Zhang, Y., D. R. Olsen, K. B. Nguyen, P. S. Olson, E. T. Rhodes, and D. Mascarenhas. 1998. Expression of eukaryotic proteins in soluble form in Escherichia coli. Protein Expr. Purif. 12: 159-165