Engineering a mammalian super producer

Journal of Chemical Technology and Biotechnology

Volumn 86, Issue 7, 2011, Pages 905-914

  Dietmair, Stefanie ^a   Nielsen, Lars K ^a   Timmins, Nicholas E ^a  

^a UNIVERSITY OF QUEENSLAND   (Australia)

Author keywords

Host cell engineering; Mammalian cell; Review

Indexed keywords

BIOPHARMACEUTICALS; CELL CYCLE; HOST CELLS; MAMMALIAN CELLS; PRODUCT YIELDS; PRODUCTION COST; PROTEIN PROCESSING; PROTEIN PRODUCTION;

CELL DEATH; MANUFACTURE;

MAMMALS;

CARBON; LACTIC ACID;

ANIMAL CELL CULTURE; APOPTOSIS; BIOENGINEERING; BIOTECHNOLOGY; CARBON METABOLISM; CELL CYCLE REGULATION; CELL METABOLISM; CELL PROLIFERATION; CELL VIABILITY; CHO CELL; CYTOLOGY; GENE OVEREXPRESSION; HOST CELL ENGINEERING; HUMAN; MAMMAL CELL; NONHUMAN; PRODUCTIVITY; PROTEIN FOLDING; PROTEIN SECRETION; PROTEIN TRANSPORT; REVIEW;

MAMMALIA;

EID: 79958762338     PISSN: 02682575     EISSN: 10974660     Source Type: Journal    
DOI: 10.1002/jctb.2576     Document Type: Review

References (117)

1. Visiongain, Biosimilars and Follow-On Biologics: Global Market Outlook 2010-2025, 139 (2010).
2. Lim Y, Wong NSC, Lee YY, Ku SCY, Wong DCF and Yap MGS, Engineering mammalian cells in bioprocessing-current achievements and future perspectives. Biotechnol Appl Biochem 55: 175-189 (2010).
3. Waltz E, GlaxoSmithKline cancer drug threatens Herceptin market. Nat Biotechnol 23: 1453-1454 (2005).
4. Berenson A, A cancer drug shows promise, at a price that many can't pay. NY Times (Print) A1: C2 (2006).
5. Birch JR and Racher AJ, Antibody production. Adv Drug Deliv Rev 58: 671-685 (2006).
6. Jain E and Kumar A, Upstream processes in antibody production: evaluation of critical parameters. Biotechnol Adv 26: 46-72 (2008).
7. Mohan C, Kim Y-G and Lee GM, Assessment of cell engineering strategies for improved therapeutic protein production in CHO cells. Biotechnol J 3: 624-630 (2008).
8. Schroeder M, Engineering eukaryotic protein factories. Biotechnol Lett 30: 187-196 (2008).
9. Sunley K and Butler M, Strategies for the enhancement of recombinant protein production from mammalian cells by growth arrest. Biotechnol Adv 28: 385-394 (2010).
10. Jacob NM, Kantardjieff A, Yusufi FN, Retzel EF, Mulukutla BC and Chuah SH, Reaching the depth of the Chinese hamster ovary cell transcriptome. Biotechnol Bioeng 105: 1002-1009 (2010).
11. Wurm FM, Production of recombinant protein therapeutics in cultivated mammalian cells. Nat Biotechnol 22: 1393-1398 (2004).
12. Singh RP, Alrubeai M, Gregory CD and Emery AN, Cell-death in bioreactors-a role for apoptosis. Biotechnol Bioeng 44: 720-726 (1994).
13. Rita Costa A, Elisa Rodrigues M, Henriques M, Azeredo J and Oliveira R, Guidelines to cell engineering for monoclonal antibody production. Eur J Pharmaceut Biopharmaceut 74: 127-138 (2010).
14. Al-Rubeai M and Singh RP, Apoptosis in cell culture. Curr Opin Biotechnol 9: 152-156 (1998).
15. Taylor RC, Cullen SP and Martin SJ, Apoptosis: controlled demolition at the cellular level. Nat Rev Mol Cell Biol 9: 231-241 (2008).
16. Mastrangelo AJ, Hardwick JM, Bex F and Betenbaugh MJ, Part I. Bcl-2 and Bcl-x(L) limit apoptosis upon infection with alphavirus vectors. Biotechnol Bioeng 67: 544-554 (2000).
17. Mastrangelo AJ, Hardwick JM, Zou S and Betenbaugh MJ, Part II. Overexpression of bcl-2 family members enhances survival of mammalian cells in response to various culture insults. Biotechnol Bioeng 67: 555-564 (2000).
18. Tey BT, Singh RP, Piredda L, Piacentini M and Al-Rubeai M, Influence of bcl-2 on cell death during the cultivation of a Chinese hamster ovary cell line expressing a chimeric antibody. Biotechnol Bioeng 68: 31-43 (2000).
19. Tey BT, Singh RP, Piredda L, Piacentini M and Al-Rubeai M, Bcl-2 mediated suppression of apoptosis in myeloma NS0 cultures. J Biotechnol 79: 147-159 (2000).
20. Vives J, Juanola S, Cairo JJ, Prats E, Cornudella L and Godia F, Protective effect of viral homologues of bcl-2 on hybridoma cells under apoptosis-inducing conditions. Biotechnol Prog 19: 84-89 (2003).
21. Sandhu KS and Al-Rubeai M, The effect of Bcl-2, YAMA, and XIAP over-expression on apoptosis and adenovirus production in HEK293 cell line. Biotechnol Bioeng 104: 752-765 (2009).
22. Reynolds JE, Li J, Craig RW and Eastman A, BCL-2 and MCL-1 expression in Chinese hamster ovary cells inhibits intracellular acidification and apoptosis induced by staurosporine. Exp Cell Res 225: 430-436 (1996).
23. Sauerwald TM, Betenbaugh MJ and Oyler GA, Inhibiting apoptosis in mammalian cell culture using the caspase inhibitor XIAP and deletion mutants. Biotechnol Bioeng 77: 704-716 (2002).
24. Figueroa B, Ailor E, Osborne D, Hardwick JM, Reff M and Betenbaugh MJ, Enhanced cell culture performance using inducible anti-apoptotic genes E1B-19K and Aven in the production of a monoclonal antibody with chinese hamster ovary cells. Biotechnol Bioeng 97: 877-892 (2006).
25. Itoh Y, Ueda H and Suzuki E, Overexpression of bcl-2, apoptosis suppressing gene: prolonged viable culture period of hybridoma and enhanced antibody production. Biotechnol Bioeng 48: 118-122 (1995).
26. Kim YG and Lee GM, Bcl-xL overexpression does not enhance specific erythropoietin productivity of recombinant CHO cells grown at 33 degrees C and 37 degrees C. Biotechnol Prog 25: 252-256 (2009).
27. Majors BS, Betenbaugh MJ, Pederson NE and Chiang GG, Mcl-1 overexpression leads to higher viabilities and increased production of humanized monoclonal antibody in Chinese hamster ovary cells. Biotechnol Prog 25: 1161-1168 (2009).
28. Chiang GG and Sisk WP, Bcl-x(L) mediates increased production of humanized monoclonal antibodies in Chinese hamster ovary cells. Biotechnol Bioeng 91: 779-792 (2005).
29. Tey BT and Al-Rubeai M, Suppression of apoptosis in perfusion culture of Myeloma NS0 cells enhances cell growth but reduces antibody productivity. Apoptosis 9: 843-852 (2004).
30. Bierau H, Perani A, Al-Rubeai M and Emery AN, A comparison of intensive cell culture bioreactors operating with hybridomas modified for inhibited apoptotic response. J Biotechnol 62: 195-207 (1998).
31. Fassnacht D, Rossing S, Singh RP, Al-Rubeai M and Portner R, Influence of bcl-2 on antibody productivity in high cell density perfusion cultures of hybridoma. Cytotechnology 30: 95-106 (1999).
32. Lee YY, Wong KTK, Tan J, Toh PC, Mao YY and Brusic V, Overexpression of heat shock proteins (HSPs) in CHO cells for extended culture viability and improved recombinant protein production. J Biotechnol 143: 34-43 (2009).
33. Havasi A, Li Z, Wang Z, Martin JL, Botla V and Ruchalski K, Hsp27 inhibits Bax activation and apoptosis via a phosphatidylinositol 3-kinase-dependent mechanism. J Biol Chem 283: 12305-12313 (2008).
34. Ishaque A, Thrift J, Murphy JE and Konstantinov K, Over-expression of Hsp70 in BHK-21 cells engineered to produce recombinant factor VIII promotes resistance to apoptosis and enhances secretion. Biotechnol Bioeng 97: 144-155 (2007).
35. Lasunskaia EB, Fridlianskaia, II, Darieva ZA, da Silva MS, Kanashiro MM and Margulis BA, Transfection of NS0 myeloma fusion partner cells with HSP70 gene results in higher hybridoma yield by improving cellular resistance to apoptosis. Biotechnol Bioeng 81: 496-504 (2003).
36. Figueroa B, Ailor E, Osborne D, Hardwick JM, Reff M and Betenbaugh MJ, Enhanced cell culture performance using inducible anti-apoptotic genes E1B-19K and Aven in the production of a monoclonal antibody with chinese hamster ovary cells. Biotechnol Bioeng 97: 877-892 (2007).
37. Mercille S, Jolicoeur P, Gervais C, Paquette D, Mosser DD and Massie B, Dose-dependent reduction of apoptosis in nutrient-limited cultures of NS/0 myeloma cells transfected with the E1B-19K adenoviral gene. Biotechnol Bioeng 63: 516-528 (1999).
38. Nivitchanyong T, Martinez A, Ishaque A, Murphy JE, Konstantinov K and Betenbaugh MJ, Anti-apoptotic genes Aven and E1B-19K enhance performance of BHK cells engineered to express recombinant factor VIII in batch and low perfusion cell culture. Biotechnol Bioeng 98: 825-841 (2007).
39. Mercille S and Massie B, Apoptosis-resistant E1B-19K-expressing NS/0 myeloma cells exhibit increased viability and chimeric antibody productivity under perfusion culture conditions. Biotechnol Bioeng 63: 529-543 (1999).
40. Sauerwald TM, Oyler GA and Betenbaugh MJ, Study of caspase inhibitors for limiting death in mammalian cell culture. Biotechnol Bioeng 81: 329-340 (2003).
41. Choi SS, Rhee WJ, Kim EJ and Park TH, Enhancement of recombinant protein production in Chinese hamster ovary cells through anti-apoptosis engineering using 30Kc6 gene. Biotechnol Bioeng 95: 459-467 (2006).
42. Koo TY, Park JH, Park HH and Park TH, Beneficial effect of 30Kc6 gene expression on production of recombinant interferon-[beta] in serum-free suspension culture of CHO cells. Process Biochem 44: 146-153 (2009).
43. Kim EJ, Rhee WJ and Park TH, Inhibition of apoptosis by a Bombyx mori gene. Biotechnol Prog 20: 324-329 (2004).
44. Dorai H, Kyung YS, Ellis D, Kinney C, Lin C and Jan D, Expression of anti-apoptosis genes alters lactate metabolism of Chinese Hamster ovary cells in culture. Biotechnol Bioeng 103: 592-608 (2009).
45. Majors BS, Betenbaugh MJ, Pederson NE and Chiang GG, Enhancement of transient gene expression and culture viability using Chinese hamster ovary cells overexpressing Bcl-x(L). Biotechnol Bioeng 101: 567-578 (2008).
46. O'Connor S, Li E, Majors BS, He L, Placone J and Baycin D, Increased expression of the integral membrane protein ErbB2 in Chinese hamster ovary cells expressing the anti-apoptotic gene Bcl-xL. Protein Expr Purif 67: 41-47 (2009).
47. Cost GJ, Freyvert Y, Vafiadis A, Santiago Y, Miller JC and Rebar E, BAK and BAX deletion using zinc-finger nucleases yields apoptosis-resistant CHO cells. Biotechnol Bioeng 105: 330-340 (2010).
48. Arden N, Majors BS, Ahn SH, Oyler G and Betenbaugh MJ, Inhibiting the apoptosis pathway using MDM2 in mammalian cell cultures. Biotechnol Bioeng 97: 601-614 (2007).
49. Wong DC, Wong KT, Nissom PM, Heng CK and Yap MG, Targeting early apoptotic genes in batch and fed-batch CHO cell cultures. Biotechnol Bioeng 95: 350-361 (2006).
50. Ifandi V and Al-Rubeai M, Stable transfection of CHO cells with the c-myc gene results in increased proliferation rates, reduces serum dependency, and induces anchorage independence. Cytotechnology 41: 1-10 (2003).
51. Ifandi V and Al-Rubeai M, Regulation of cell proliferation and apoptosis in CHO-K1 cells by the coexpression of c-Myc and Bcl-2. Biotechnol Prog 21: 671-677 (2005).
52. Pelengaris S, Khan M and Evan G, c-MYC: more than just a matter of life and death. Nat Rev Cancer 2: 764-776 (2002).
53. Kuystermans D and Al-Rubeai M, cMyc increases cell number through uncoupling of cell division from cell size in CHO cells. BMC Biotechnol 9: 76 (2009).
54. Bi JX, Shuttleworth J and Al-Rubeai M, Uncoupling of cell growth and proliferation results in enhancement of productivity in p21CIP1-arrested CHO cells. Biotechnol Bioeng 85: 741-749 (2004).
55. Majors BS, Arden N, Oyler GA, Chiang GG, Pederson NE and Betenbaugh MJ, E2F-1 overexpression increases viable cell density in batch cultures of Chinese hamster ovary cells. J Biotechnol 138: 103-106 (2008).
56. Jaluria P, Betenbaugh M, Konstantopoulos K and Shiloach J, Enhancement of cell proliferation in various mammalian cell lines by gene insertion of a cyclin-dependent kinase homolog. BMC Biotechnol 7: 71 (2007).
57. Park H, Kim IH, Kim IY, Kim KH and Kim HJ, Expression of carbamoyl phosphate synthetase I and ornithine transcarbamoylase genes in Chinese hamster ovary dhfr-cells decreases accumulation of ammonium ion in culture media. J Biotechnol 81: 129-140 (2000).
58. Paredes C, Prats E, Cairo JJ, Azorin F, Cornudella L and Godia F, Modification of glucose and glutamine metabolism in hybridoma cells through metabolic engineering. Cytotechnology 30: 85-93 (1999).
59. Bell SL, Bebbington C, Scott MF, Wardell JN, Spier RE and Bushell ME, Genetic engineering of hybridoma glutamine metabolism. Enzyme Microb Technol 17: 98-106 (1995).
60. Chen K, Liu Q, Xie L, Sharp PA and Wang DI, Engineering of a mammalian cell line for reduction of lactate formation and high monoclonal antibody production. Biotechnol Bioeng 72: 55-61 (2001).
61. Kim SH and Lee GM, Down-regulation of lactate dehydrogenase-A by siRNAs for reduced lactic acid formation of Chinese hamster ovary cells producing thrombopoietin. Appl Microbiol Biotechnol 74: 152-159 (2007).
62. Irani N, Wirth M, van Den Heuvel J and Wagner R, Improvement of the primary metabolism of cell cultures by introducing a new cytoplasmic pyruvate carboxylase reaction. Biotechnol Bioeng 66: 238-246 (1999).
63. Irani N, Beccaria AJ and Wagner R, Expression of recombinant cytoplasmic yeast pyruvate carboxylase for the improvement of the production of human erythropoietin by recombinant BHK-21 cells. J Biotechnol 93: 269-282 (2002).
64. Elias CB, Carpentier E, Durocher Y, Bisson L, Wagner R and Kamen A, Improving glucose and glutamine metabolism of human HEK 293 and Trichoplusia ni insect cells engineered to express a cytosolic pyruvate carboxylase enzyme. Biotechnol Prog 19: 90-97 (2003).
65. Fogolin MB, Wagner R, Etcheverrigaray M and Kratje R, Impact of temperature reduction and expression of yeast pyruvate carboxylase on hGM-CSF-producing CHO cells. J Biotechnol 109: 179-191 (2004).
66. Wlaschin KF and Hu WS, Engineering cell metabolism for high-density cell culture via manipulation of sugar transport. J Biotechnol 131: 168-176 (2007).
67. Sunley K and Butler M, Strategies for the enhancement of recombinant protein production from mammalian cells by growth arrest. Biotechnol Adv 28: 385-394 (2010).
68. Koester M, Kirchhoff S, Schlaper F and Hauser H, Proliferation control of mammalian cells by the tumour suppressor IRF-1. Cytotechnology I: 67-75 (1995).
69. Kirchhoff S, Kröger A, Cruz H, Tümmler M, Schaper F and Köster M, Regulation of cell growth by IRF-1 in BHK-21 cells. Cytotechnology: 147-156 (1996).
70. Geserick C, Bonarius HP, Kongerslev L, Hauser H and Mueller PP, Enhanced productivity during controlled proliferation of BHK cells in continuously perfused bioreactors. Biotechnol Bioeng 69: 266-274 (2000).
71. Carvalhal AV, Moreira JL and Carrondo MJ, Strategies to modulate BHK cell proliferation by the regulation of IRF-1 expression. J Biotechnol 92: 47-59 (2001).
72. Fussenegger M, Mazur X and Bailey JE, A novel cytostatic process enhances the productivity of Chinese hamster ovary cells. Biotechnol Bioeng 55: 927-939 (1997).
73. Mazur X, Fussenegger M, Renner WA and Bailey JE, Higher productivity of growth-arrested Chinese hamster ovary cells expressing the cyclin-dependent kinase inhibitor p27. Biotechnol Prog 14: 705-713 (1998).
74. Fussenegger M, Schlatter S, Datwyler D, Mazur X and Bailey JE, Controlled proliferation by multigene metabolic engineering enhances the productivity of Chinese hamster ovary cells. Nat Biotechnol 16: 468-472 (1998).
75. Watanabe S, Shuttleworth J and Al-Rubeai M, Regulation of cell cycle and productivity in NS0 cells by the over-expression of p21CIP1. Biotechnol Bioeng 77: 1-7 (2002).
76. Werner NS, Weber W, Fussenegger M and Geisse S, A gas-inducible expression system in HEK.EBNA cells applied to controlled proliferation studies by expression of p27(Kip1). Biotechnol Bioeng 96: 1155-1166 (2007).
77. Lloyd DR, Holmes P, Jackson LP, Emery AN and Al-Rubeai M, Relationship between cell size, cell cycle and specific recombinant protein productivity. Cytotechnology 34: 59-70 (2000).
78. Carvalhal AV, Marcelino I and Carrondo MJ, Metabolic changes during cell growth inhibition by p27 overexpression. Appl Microbiol Biotechnol 63: 164-173 (2003).
79. Meents H, Enenkel B, Werner RG and Fussenegger M, p27Kip1-mediated controlled proliferation technology increases constitutive sICAM production in CHO-DUKX adapted for growth in suspension and serum-free media. Biotechnol Bioeng 79: 619-627 (2002).
80. Kumar N, Gammell P and Clynes M, Proliferation control strategies to improve productivity and survival during CHO based production culture: a summary of recent methods employed and the effects of proliferation control in product secreting CHO cell lines. Cytotechnology 53: 33-46 (2007).
81. Dinnis DM and James DC, Engineering mammalian cell factories for improved recombinant monoclonal antibody production: lessons from nature? Biotechnol Bioeng 91: 180-189 (2005).
82. Bibila TA and Flickinger MC, Use of a structured kinetic model of antibody synthesis and secretion for optimization of antibody production systems: I. Steady-state analysis. Biotechnol Bioeng 39: 251-261 (1992).
83. Dinnis DM, Stansfield SH, Schlatter S, Smales CM, Alete D and Birch JR, Functional proteomic analysis of GS-NS0 murine myeloma cell lines with varying recombinant monoclonal antibody production rate. Biotechnol Bioeng 94: 830-841 (2006).
84. Hwang SO, Chung JY and Lee GM, Effect of doxycycline-regulated ERp57 expression on specific thrombopoietin productivity of recombinant CHO cells. Biotechnol Prog 19: 179-184 (2003).
85. 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).
86. 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).
87. 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).
88. 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).
89. Borth N, Mattanovitch D, Kunert R and Katinger H, Effect of increased expression of protein disulfide isomerase and heavy chain binding protein GRP78 on antibody expression in recombinant CHO cells. Biotechnol Prog 21: 106-111 (2004).
90. 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).
91. 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).
92. Ohya T, Hayashi T, Kiyama E, Nishii H, Miki H and Kobayashi K, Improved production of recombinant human antithrombin III in Chinese hamster ovary cells by ATF4 overexpression. Biotechnol Bioeng 100: 317-324 (2008).
93. Ku SCY, Ng DTW, Yap MGS 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).
94. Omasa T, Takami T, Ohya T, Kiyama E, Hayashi T and Nishii H, Overexpression of GADD34 enhances production of recombinant human antithrombin III in Chinese hamster ovary cells. J Biosci Bioeng 106: 568-573 (2008).
95. Li B, Gao B, Ye L, Han X, Wang W and Kong L, Hepatitis B virus X protein (HBx) activates ATF6 and IRE1-XBP1 pathways of unfolded protein response. Virus Res 124: 44-49 (2007).
96. Jin F, Kretschmer PJ, Harkins RN and Hermiston TW, Enhanced protein production using HBV X protein (HBx), and synergy when used in combination with XBP1s in BHK21 cells. Biotechnol Bioeng 105:(2010).
97. 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).
98. Peng RW, Guetg C, Tigges M and Fussenegger M, The vesicle-trafficking protein munc18b increases the secretory capacity of mammalian cells. Metab Eng 12: 18-25 (2010).
99. Dorai H, Kyung YS, Ellis D, Kinney C, Lin CB and Jan D, Expression of anti-apoptosis genes alters lactate metabolism of Chinese hamster ovary cells in culture. Biotechnol Bioeng 103: 592-608 (2009).
100. Shusta EV, Raines RT, Pluckthun A and Wittrup KD, Increasing the secretory capacity of Saccharomyces cerevisiae for production of single-chain antibody fragments. Nat Biotechnol 16: 773-777 (1998).
101. Kim MD, Han KC, Kang HA, Rhee SK and Seo JH, Coexpression of BiP increased antithrombotic hirudin production in recombinant Saccharomyces cerevisiae. J Biotechnol 101: 81-87 (2003).
102. Damasceno LM, Anderson KA, Ritter G, Cregg JM, Old LJ and Batt CA, Cooverexpression of chaperones for enhanced secretion of a single-chain antibody fragment in Pichia pastoris. Appl Microbiol Biotechnol 74: 381-389 (2007).
103. Kuystermans D, Dunn MJ and Al-Rubeai M, A proteomic study of cMyc improvement of CHO culture. BMC Biotechnol 10: 25 (2010).
104. Park SJ, Lee SY, Cho J, Kim TY, Lee JW and Park JH, Global physiological understanding and metabolic engineering of microorganisms based on omics studies. Appl Microbiol Biotechnol 68: 567-579 (2005).
105. Park JH, Lee KH, Kim TY and Lee SY, Metabolic engineering of Escherichia coli for the production of L-valine based on transcriptome analysis and in silico gene knockout simulation. Proc Natl Acad Sci USA 104: 7797-7802 (2007).
106. Im JH, Kim MG and Kim ES, Comparative transcriptome analysis for avermectin overproduction via Streptomyces avermitilis microarray system. J Microbiol Biotechnol 17: 534-538 (2007).
107. Kizer L, Pitera DJ, Pfleger BF and Keasling JD, Application of functional genomics to pathway optimization for increased isoprenoid production. Appl Environ Microbiol 74: 3229-3241 (2008).
108. Lee KH, Park JH, Kim TY, Kim HU and Lee SY, Systems metabolic engineering of Escherichia coli for L-threonine production. Mol Syst Biol 3: 149 (2007).
109. Lee SJ, Lee DY, Kim TY, Kim BH, Lee J and Lee SY, Metabolic engineering of Escherichia coli for enhanced production of succinic acid, based on genome comparison and in silico gene knockout simulation. Appl Environ Microbiol 71: 7880-7887 (2005).
110. Arden N and Betenbaugh MJ, Life and death in mammalian cell culture: strategies for apoptosis inhibition. Trends Biotechnol 22: 174-180 (2004).
111. Orrenius S, Zhivotovsky B and Nicotera P, Regulation of cell death: the calcium-apoptosis link. Nat Rev Mol Cell Biol 4: 552-565 (2003).
112. Szegezdi E, Fitzgerald U and Samali A, Caspase-12 and ER-stress-mediated apoptosis: the story so far. Ann N Y Acad Sci 1010: 186-194 (2003).
113. Dehay C and Kennedy H, Cell-cycle control and cortical development. Nat Rev Neurosci 8: 438-450 (2007).
114. Coller HA, What's taking so long? S-phase entry from quiescence versus proliferation. Nat Rev Mol Cell Biol 8: 667-670 (2007).
115. Dzau VJ, Braun-Dullaeus RC and Sedding DG, Vascular proliferation and atherosclerosis: new perspectives and therapeutic strategies. Nat Med 8: 1249-1256 (2002).
116. Ma Y and Hendershot LM, The role of the unfolded protein response in tumour development: friend or foe? Nat Rev Cancer 4: 966-977 (2004).
117. Hotamisligil GS, Endoplasmic reticulum stress and atherosclerosis. Nat Med 16: 396-399 (2010).