The impact of phosphate scarcity on pharmaceutical protein production in S. cerevisiae: Linking transcriptomic insights to phenotypic responses

Microbial Cell Factories

Volumn 10, Issue , 2011, Pages

  Kazemi Seresht, Ali ^a,b   Palmqvist, Eva A ^a   Olsson, Lisbeth ^b  

^a NOVO NORDISK A S   (Denmark)

^b CHALMERS UNIVERSITY OF TECHNOLOGY   (Sweden)

Author keywords

Chemostat cultivations; Heterologous protein production; Human insulin; Phosphate regulation; Secretory flux; Tpi1 promoter

Indexed keywords

GLYCEROL; HUMAN INSULIN; PHOSPHATE; SACCHAROMYCES CEREVISIAE PROTEIN; TPI1 PROTEIN; UNCLASSIFIED DRUG; RECOMBINANT PROTEIN;

ARTICLE; BIOMASS; CARBON TRANSPORT; CELL DENSITY; CONTROLLED STUDY; DRY WEIGHT; FUNGAL BIOMASS; FUNGAL CELL CULTURE; NONHUMAN; PHENOTYPE; PROTEIN EXPRESSION; PROTEIN SECRETION; SACCHAROMYCES CEREVISIAE; TRANSCRIPTOMICS; TRANSPORT AT THE CELLULAR LEVEL; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENETICS; GROWTH, DEVELOPMENT AND AGING; HUMAN; METABOLISM; PROTEIN TRANSPORT;

EUKARYOTA; SACCHAROMYCES CEREVISIAE;

GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION, FUNGAL; HUMANS; INSULIN, REGULAR, HUMAN; PHENOTYPE; PHOSPHATES; PROTEIN TRANSPORT; RECOMBINANT PROTEINS; SACCHAROMYCES CEREVISIAE; SACCHAROMYCES CEREVISIAE PROTEINS;

EID: 82755162477     PISSN: None     EISSN: 14752859     Source Type: Journal    
DOI: 10.1186/1475-2859-10-104     Document Type: Article

References (37)

1. Porro D, Gasser B, Fossati T, Maurer M, Branduardi P, Sauer M, et al. Production of recombinant proteins and metabolites in yeasts: when are these systems better than bacterial production systems?. Applied Microbiology and Biotechnology 2011, 89:939-48. 10.1007/s00253-010-3019-z, 21125266.
2. Walsh G. Therapeutic insulins and their large-scale manufacture. Applied Microbiology and Biotechnology 2005, 67:151-9. 10.1007/s00253-004-1809-x, 15580495.
3. Sauer M, Porro D, Mattanovich D, Branduardi P. Microbial production of organic acids: expanding the markets. Trends in Biotechnology 2008, 26:100-8. 10.1016/j.tibtech.2007.11.006, 18191255.
4. Jarboe LR, Zhang X, Wang X, Moore JC, Shanmugam KT, Ingram LO. Metabolic engineering for production of biorenewable fuels and chemicals: contributions of synthetic biology. Journal of Biomedicine & Biotechnology 2010, 2010:761042.
5. Otero JM, Nielsen J. Industrial systems biology. Biotechnology and Bioengineering 2010, 105:439-60. 10.1002/bit.22592, 19891008.
6. Robinson A, Wittrup KD. Constitutive overexpression of secreted heterologous proteins decreases extractable BiP and protein disulfide isomerase levels in Saccharomyces cerevisiae. Biotechnology Progress 1995, 11:171-7. 10.1021/bp00032a009, 7536423.
7. Kjeldsen T. Yeast secretory expression of insulin precursors. Applied Microbiology and Biotechnology 2000, 54:277-86. 10.1007/s002530000402, 11030562.
8. Graf A, Dragosits M, Gasser B. Yeast systems biotechnology for the production of heterologous proteins. FEMS Yeast 2009, 9:335-348.
9. Boer VM, Crutchfield CA, Bradley PH, Botstein D, Rabinowitz JD. Growth-limiting intracellular metabolites in yeast growing under diverse nutrient limitations. Molecular Biology of the Cell 2010, 21:198-211. 10.1091/mbc.E09-07-0597, 2801714, 19889834.
10. Kolkman A, Daran-Lapujade P, Fullaondo A, Olsthoorn MMA, Pronk JT, Slijper M, et al. Proteome analysis of yeast response to various nutrient limitations. Molecular Systems Biology 2006, 2:2006-0026. 1681510, 16788596.
11. Brauer MJ, Huttenhower C, Airoldi EM, Rosenstein R, Matese JC, Gresham D, et al. Coordination of Growth Rate, Cell Cycle, Stress Response, and Metabolic Activity in Yeast. Molecular Biology of the Cell 2008, 19:352-367. 10.1091/mbc.E07-08-0779, 2174172, 17959824.
12. Gutteridge A, Pir P, Castrillo JI, Charles PD, Lilley KS, Oliver SG. Nutrient control of eukaryote cell growth: a systems biology study in yeast. BMC Biology 2010, 8:68. 10.1186/1741-7007-8-68, 2895586, 20497545.
13. Conesa A, Nueda MJ, Ferrer A, Talón M. maSigPro: a method to identify significantly differential expression profiles in time-course microarray experiments. Bioinformatics (Oxford, England) 2006, 22:1096-102.
14. Smets B, Ghillebert R, De Snijder P, Binda M, Swinnen E, De Virgilio C, et al. Life in the midst of scarcity: adaptations to nutrient availability in Saccharomyces cerevisiae. Current Genetics 2010, 56:1-32. 10.1007/s00294-009-0287-1, 20054690.
15. Mouillon J-M, Persson BL. New aspects on phosphate sensing and signalling in Saccharomyces cerevisiae. FEMS Yeast Research 2006, 6:171-6. 10.1111/j.1567-1364.2006.00036.x, 16487340.
16. Ogawa N, DeRisi J, Brown PO. New components of a system for phosphate accumulation and polyphosphate metabolism in Saccharomyces cerevisiae revealed by genomic expression analysis. Molecular Biology of the Cell 2000, 11:4309-21. 15074, 11102525.
17. Lenburg M. Signaling phosphate starvation. Trends in Biochemical Sciences 1996, 21:383-387.
18. Lee Y-S, Huang K, Quiocho FA, O'Shea EK. Molecular basis of cyclin-CDK-CKI regulation by reversible binding of an inositol pyrophosphate. Nature Chemical Biology 2008, 4:25-32. 2367112, 18059263.
19. Kaffman A, Rank NM, O'Neill EM, Huang LS, O'Shea EK. The receptor Msn5 exports the phosphorylated transcription factor Pho4 out of the nucleus. Nature 1998, 396:482-486. 10.1038/24898, 9853758.
20. Auesukaree C, Tochio H, Shirakawa M, Kaneko Y, Harashima S. Plc1p, Arg82p, and Kcs1p, enzymes involved in inositol pyrophosphate synthesis, are essential for phosphate regulation and polyphosphate accumulation in Saccharomyces cerevisiae. The Journal of Biological Chemistry 2005, 280:25127-33. 10.1074/jbc.M414579200, 15866881.
21. Lee Y-S, Mulugu S, York JD, O'Shea EK. Regulation of a cyclin-CDK-CDK inhibitor complex by inositol pyrophosphates. Science 2007, 316:109-12. 10.1126/science.1139080, 2211727, 17412959.
22. Kramer RA, DeChiara TM, Schaber MD, Hilliker S. Regulated expression of a human interferon gene in yeast: control by phosphate concentration or temperature. Proceedings of the National Academy of Sciences of the United States of America 1984, 81:367-70. 10.1073/pnas.81.2.367, 344677, 6320183.
23. Blondeau K, Boutur O, HeTene B, Moulin G, Galzy P. Influence of culture conditions on the production of heterologous interleukin 1beta by Kluyveromyces lactis. Biotechnology Techniques 1993, 7:609-614.
24. Kulaev I, Kulakovskaya T. Polyphosphate and phosphate pump. Annual Review of Microbiology 2000, 54:709-34. 10.1146/annurev.micro.54.1.709, 11018142.
25. Angus R, Lester WW. Turnover of lnositol and Phosphorus Containing Lipids in Saccharomyces cerevisiae; Extracellular Accumulation Derived of Glycerophosphorylinositol from Phosphatidylinositol. Archives of Biochemistry and Biophysics 1972, 151:483-495. 10.1016/0003-9861(72)90525-5, 4339932.
26. Almaguer C, Mantella D, Perez E, Patton-Vogt J. Inositol and phosphate regulate GIT1 transcription and glycerophosphoinositol incorporation in Saccharomyces cerevisiae. Eukaryotic Cell 2003, 2:729. 10.1128/EC.2.4.729-736.2003, 178388, 12912892.
27. Carroll AS, Bishop AC, DeRisi JL, Shokat KM, O'Shea EK. Chemical inhibition of the Pho85 cyclin-dependent kinase reveals a role in the environmental stress response. Proceedings of the National Academy of Sciences 2001, 98:12578-83.
28. Almaguer C, Cheng W, Nolder C, Patton-Vogt J. Glycerophosphoinositol, a novel phosphate source whose transport is regulated by multiple factors in Saccharomyces cerevisiae. The Journal of Biological Chemistry 2004, 279:31937-42. 10.1074/jbc.M403648200, 15145930.
29. Pahlman AK, Granath K, Ansell R, Hohmann S, Adler L. The yeast glycerol 3-phosphatases Gpp1p and Gpp2p are required for glycerol biosynthesis and differentially involved in the cellular responses to osmotic, anaerobic, and oxidative stress. The Journal of Biological Chemistry 2001, 276:3555-63. 10.1074/jbc.M007164200, 11058591.
30. Ansell R, Granath K, Hohmann S, Thevelein JM, Adler L. The two isoenzymes for yeast NAD + -dependent glycerol 3-phosphate dehydrogenase encoded by GPD1 and GPD2 have distinct roles in and redox regulation osmoadaptation. EMBO Journal 1997, 16:2179-2187. 10.1093/emboj/16.9.2179, 1169820, 9171333.
31. Lu S-P, Lin S-J. Phosphate responsive signaling pathway is a novel component of NAD+ metabolism in Saccharomyces cerevisiae. The Journal of Biological Chemistry 2011, 286:14271-14281. 10.1074/jbc.M110.217885, 21349851.
32. Scott EW, Baker HV. Concerted action of the transcriptional activators REB1, RAP1, and GCR1 in the high-level expression of the glycolytic gene TPI. Molecular and Cellular Biology 1993, 13:543-50. 358933, 8417350.
33. Verduyn C, Postma E, Scheffers WA, Van Dijken JP. Effect of benzoic acid on metabolic fluxes in yeasts: a continuous-culture study on the regulation of respiration and alcoholic fermentation. Yeast (Chichester, England) 1992, 8:501-17.
34. Gietz RD, Woods RA. Genetic transformation of yeast. Biotechniques 2001, 30:816-831.
35. Christianson TW, Sikorski RS, Dante M, Shero JH, Hieter P. Multifunctional yeast high-copy-number shuttle vectors. Gene 1992, 110:119-22. 10.1016/0378-1119(92)90454-W, 1544568.
36. Kjeldsen T, Ludvigsen S, Diers I, Balschmidt P, Sorensen AR, Kaarsholm NC. Engineering-enhanced protein secretory expression in yeast with application to insulin. The Journal of Biological Chemistry 2002, 277:18245-8. 10.1074/jbc.C200137200, 11923277.
37. Kjeldsen T, Brandt J, Andersen AS, Egel-Mitani M, Hach M, Pettersson AF, et al. A removable spacer peptide in an alpha-factor-leader/insulin precursor fusion protein improves processing and concomitant yield of the insulin precursor in Saccharomyces cerevisiae. Gene 1996, 170:107-12. 10.1016/0378-1119(95)00822-5, 8621069.