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Physiological aspects of growth and recombinant DNA stability inSaccharomyces cerevisiae

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Abstract

Despite the fact that plasmid stability in the yeastSaccharomyces cerevisiae is influenced by both genetical and physiological parameters most attention has been focussed on the former. Physiological factors affecting the stability of plasmids have been poorly characterized despite the need for such information in order to optimize the use ofS. cerevisiae as a host for recombinant protein production processes. The physiology of wild typeS. cerevisiae differs considerably when grown using different cultivation techniques. A limited amount of phenomenological data has been reported concerning plasmid instability effects under these different conditions and in this article these have been collected together with the intention of providing an overview to instability effects and to try and propose reasons as to how the physiological response to different growth conditions can be manifested as stability/instability effects.

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References

  • Aar PCvan der, Lopes TS, Klootwijk J, Groeneveld Ph, Verseveld HWvan & Stouthamer AH (1990) Consequences of phosphoglycerate kinase overproduction for the growth and physiology ofSaccharomyces cerevisiae. Appl. Microbiol. Biotechnol. 32: 577–587

    Google Scholar 

  • Bailey JE, DaSilva NA, Peretti SW, Seo J-H & Srienc F (1986) Studies of host plasmid interactions in recombinant micro-organisms. Ann. NY. Acad. Sci. 469: 194–211

    Google Scholar 

  • Barford JP & Hall RJ (1976) Estimation of the length of cell cycle phases from asynchronous cultures ofSaccharomyces cerevisiae. Exp. Cell Res. 102: 276–284

    Google Scholar 

  • Bentley WE, Mirajalili N, Andersen DA, Davis RH & Kompala DS (1990) Plasmid-encoded protein: The principal factor in the ‘metabolic burden’ associated with recombinant bacteria. Biotechnol. Bioeng. 35: 668–681

    Google Scholar 

  • Bitter GA, Egan KM, Koski RA, Jones MO, Elliott SG & Giffin JC (1987) Expression and secretion vectors for yeast. Meth. Enzymol. 153: 516–544

    Google Scholar 

  • Britton NF & Wheals AE (1987) Mathematical models for a Go phase inSaccharomyces cerevisiae. J. Theor. Biol. 125: 269–281

    Google Scholar 

  • Broach JR & Hicks JB (1980) Replication and recombination functions associated with the yeast plasmid 2 μm circle. Cell 21: 501–508

    Google Scholar 

  • Bugeja VC, Piggott JR & Carter BLA (1982) Differentiation ofSaccharomyces cerevisiae at slow growth rates in glucose limited continuous culture. J. Gen. Microbiol. 128: 2707–2714

    Google Scholar 

  • Bugeja VC, Kleinman MJ, Stanbury PF & Gingold EB (1989) The segregation of the 2 μm-based yeast plasmid pJDB248 breaks down under conditions of glucose-limited growth. J. Gen. Microbiol. 135: 2891–2897

    Google Scholar 

  • Caunt P, Impoolsup A & Greenfield PF (1989) The effect of oxygen limitation on stability of a recombinant plasmid inSaccharomyces cerevisiae. Biotechnol. Lett. 11: 5–10

    Google Scholar 

  • Caunt P, Impoolsup A & Greenfield PF (1990) A method for the stabilization of recombinant plasmids in yeast. J. Biotechnol. 14: 311–320

    Google Scholar 

  • Copella SJ & Dhurjati P (1989) α-factor directed expression of the human epidermal growth factor inSaccharomyces cerevisiae. Biotechnol. Bioeng. 33: 976–983

    Google Scholar 

  • DiBiasio D & Sardonini C (1986) Stability of continuous culture with recombinant organisms. Ann. N.Y. Acad. Sci. 469: 111–117

    Google Scholar 

  • Doran PM & Bailey JE (1986) Effects of immobilization on growth, fermentation properties and macromolecular composition ofSaccharomyces cerevisiae attached to gelatin. Biotechnol. Bioeng. 28: 73–87

    Google Scholar 

  • Egli T & Mason CA (1991) Mixed Cultures and Mixed Substrates. In: Goldberg I & Rokem S (Eds) The Biology of the Methylotrophs (pp 00-00) Butterworth Press

  • Erhart E & Hollenberg CP (1983) The presence of a defective LEU2 gene on 2 μ DNA recombinant plasmids is responsible for curing and high copy number. J. Bacteriol. 156: 625–635

    Google Scholar 

  • Fieschko JC, Egan KM, Ritch T, Koski RA, Jones M & Bitter G (1987) Controlled expression and purification of human immune interferon from high cell density fermentations ofSaccharomyces cerevisiae. Biotechnol. Bioeng. 29: 1113–1121

    Google Scholar 

  • Futcher AB (1986) Copy number amplification of the 2 micron plasmid ofSaccharomyces cerevisiae. J. Theor. Biol. 119: 197–204

    Google Scholar 

  • Futcher AB & Cox BS (1984) Copy number and the stability of 2 μm circle-based artificial plasmids ofSaccharomyces cerevisiae. J. Bacteriol. 157: 283–290

    Google Scholar 

  • Gerbaud C & Guérineau M (1980) 2 μm plasmid copy number in different yeast strains and repatition of endogenous and 2 μm chimeric plasmids in transformed strains. Current Genetics 1: 219–228

    Google Scholar 

  • Golpal CV, Broad D & Lloyd D (1989) Bioenergetic consequences of protein overexpression inSaccharomyces cerevisiae. Appl. Microbiol. Biotechnol. 30: 160–165

    Google Scholar 

  • Hartwell LH & Unger MW (1977) Unequal division inSaccharomyces cerevisiae and its implication for the control of cell division. J. Cell Biol. 75: 422–435

    Google Scholar 

  • Hinnen A, Hicks JB & Fink GR (1978) Transformation of yeast Proc. Natl. Acad. Sci. USA 75: 1929–1933

    Google Scholar 

  • Hjortsu MA, Dennis KE & Bailey JE (1985) Quantitative characterization of plasmid instability inSaccharomyces cerevisiae using flow cytometry cell sorting. Biotechnol. Lett. 7: 21–24

    Google Scholar 

  • Impoolsup A, Caunt P & Greenfield PF (1989) Effect of growth rates on stability of a recombinant plasmid during continuous culture ofSaccharomyces cerevisiae in non-selective medium. J. Biotechnol. 10: 171–180

    Google Scholar 

  • Jayaram M, Li YY & Broach JR (1983) The yeast plasmid 2 μ circle encodes components required for its high copy propagation. Cell 34: 95–101

    Google Scholar 

  • Johnston GC, Pringle JR & Hartwell LH (1977) Coordination of growth with cell division in the yeastSaccharomyces cerevisiae. Exp. Cell Res. 105: 79–98

    Google Scholar 

  • Johnston GC, Singer RA, Sharrow SO & Slater ML (1980) Cell division in the yeastSaccharomyces cerevisiae growing at different growth rates. J. Gen. Microbiol. 118: 479–484

    Google Scholar 

  • Kikuchi Y & Toh-e A (1986) A nuclear gene ofSaccharomyces cerevisiae needed for stable maintenance of plasmids. Mol. Cell Biol. 6: 4053–4059

    Google Scholar 

  • Kleinman MJ, Gingold EB & Stanbury PF (1986) The stability of the yeast plasmid pJDB248 depends on the growth rate of the culture. Biotechnol. Lett. 8: 225–230

    Google Scholar 

  • Ligan JM, Bolen PL, Hill DS & Bothast RJ (1989) Physiological and biochemical characterization of linear DNA plasmids of the yeastPichia inositovora. Plasmid 21: 185–194

    Google Scholar 

  • Lopes TS, Klootwijk J, van derAar PC, vanHeerikhuizen H, Raué HA & Planta RJ (1989) High copy-number integration into the ribosomal DNA ofSaccharomyces cerevisiae a new vector for high-level expression. Gene 79: 199–206

    Google Scholar 

  • Lord PG & Wheals AE (1980) Asymmetrical division ofSaccharomyces cerevisiae. J. Bacteriol. 142: 808–818

    Google Scholar 

  • Lord PG & Wheals AE (1981) Variability in individual cell cycles ofSaccharomyces cerevisiae. J. Cell Sci. 50: 361–376

    Google Scholar 

  • Marquet M, Alouani S, Haas ML, Loison G & Brown SW (1987) Double mutants ofSaccharomyces cerevisiae harbour stable plasmids. Stable expression of a eukaryotic gene and the influence of host physiology during continuous culture. J. Biotechnol. 6: 135–145

    Google Scholar 

  • Mason CA & Hamer G (1987) Cryptic growth inKlebsiella pneumoniae. Appl. Microbiol. Biotechnol. 25: 577–584

    Google Scholar 

  • Mason CA & Bailey JE (1989) Effects of plasmid presence on growth and enzyme activity ofEscherichia coli DH5α. Appl. Microbiol. Biotechnol. 32: 54–60

    Google Scholar 

  • Mead DJ, Gardner DCJ & Oliver SG (1986a) The yeast 2 micron plasmid.: Strategies for the survival of a selfish DNA. Mol. Gen. Genet. 205: 417–421

    Google Scholar 

  • Mead DJ, Gardner DCJ & Oliver SG (1986b) Enhanced stability of a 2 μ-based recombinant plasmid in diploid yeast. Biotechnol. Lett. 8: 391–396

    Google Scholar 

  • Murray AW & Szostak JW (1983) Pedigree analysis of plasmid segregation in yeast. Cell 34: 961–970

    Google Scholar 

  • Newlon CS (1989) Deoxyribonucleic acid organization and replication. In: Rose AH & Harrison JS (Eds) The Yeasts, Vol 3 (pp 57–116) Academic Press London

    Google Scholar 

  • Parent SA, Fenimore CM & Bostian KA (1985) Vector systems for the expression analysis and cloning of DNA sequences inSaccharomyces cerevisiae. Yeast 1: 83–138

    Google Scholar 

  • Piñon R (1978) Folded chromosome in non-cycling yeast cells. Evidence for a characteristic Go phase. Chromosoma 67: 263–274

    Google Scholar 

  • Piñon R (1979) A probe into nuclear events during the cell cycle ofSaccharomyces cerevisiae incdc mutants with arrest in G1. Chromosoma 70: 337–352

    Google Scholar 

  • Piñon R & Pratt D (1979) Folded chromosomes of mating factor arrested cells: comparison with Go arrest. Chromosoma 73: 117–129

    Google Scholar 

  • Postma E, Verduyn C, Scheffers WA & vanDijken JP (1989) Enzymic analysis of the crabtree effect in glucose-limited chemostat cultures ofSaccharomyces cerevisiae. Appl. Environ. Microbiol. 55: 468–477

    Google Scholar 

  • Rivin CJ & Fangman WL (1980a) Cell cycle phase expansion in nitrogen limited cultures ofSaccharomyces cerevisiae. J. Cell Biol. 85: 96–107

    Google Scholar 

  • Rivin CJ & Fangman WL (1980b) Replication fork rate and origin activation during the S phase ofSaccharomyces cerevisiae. J. Cell Biol. 85: 108–115

    Google Scholar 

  • Scheper Th, Hoffman H & Schügerl K (1987) Flow cytometric studies during culture ofSaccharomyces cerevisiae. Enz. Microb. Technol. 9: 399–405

    Google Scholar 

  • Senn H (1989) Kinetik und regulation des Zuckerabbaus vonEscherichia coli ML 30 bei tiefen Zuckerkonzentrationen. Dissertation ETH Nr. 8831

  • Sigurdson DC, Gaarder ME & Livingston DM (1981) Characterization of the transmission during cytoductant formation of the 2 μm DNA plasmid fromSaccharomyces. Mol. Gen. Genet. 183: 59–65

    Google Scholar 

  • Som T, Armstrong KA, Volkert FC & Broach JR (1988) Autoregulation of 2 μm circle gene expression provides a model for maintenance of stable plasmid copy levels. Cell 52: 27–37

    Google Scholar 

  • Spalding A & Tuite MF (1989) Host-plasmid interactions inSaccharomyces cerevisiae: Effect of host ploidy on plasmid stability and copy number. J. Gen. Microbiol. 135: 1037–1045

    Google Scholar 

  • Srienc F, Campbell JL & Bailey JE (1986) Analysis of unstable recombinantSaccharomyces cerevisiae population growth in selection medium. Biotechnol. Bioeng. 28: 996–1006

    Google Scholar 

  • Stephens ML & Lyberatos G (1988) Effect of cycling on the stability of plasmid-bearing microorganisms in continuous culture. Biotechnol. Bioeng. 31: 464–469

    Google Scholar 

  • Sturley SL & Young TW (1988) Genetic Manipulation of commercial yeast strains. In: Russell GE (Ed) Yeast Biotechnology (pp 1–38) Intercept, Wimbourne Dorset

    Google Scholar 

  • Thompson PW & Wheals AE (1980) Asymmetrical division ofSaccharomyces cerevisiae in glucose limited chemostat culture. J. Gen. Microbiol. 121: 401–409

    Google Scholar 

  • Toh-e A, Tada S & Oshima Y (1982) 2 μm DNA-like plasmids in the osmophilic haploid yeastSaccharomyces cerevisiae. J. Bacteriol. 151: 1380–1390

    Google Scholar 

  • Topiwala HH & Hamer G (1971) Effect of wall growth in steady state continuous cultures. Biotechnol. Bioeng. 13: 919–922

    Google Scholar 

  • Tsai LB, Mann M, Morris F, Rotgers C & Fenton D (1987) The effect of organic nitrogen and glucose on the production of recombinant human insulin-like growth factor in high cell densityEscherichia coli fermentations. J. Ind. Microbiol. 2: 181–187

    Google Scholar 

  • Volkert FC, Wilson DW & Broach JR (1989) Deoxyribonucleic acid plasmids in yeasts. Microbiol. Rev. 53: 299–317

    Google Scholar 

  • Walls EL & Gainer JL (1989) Retention of plasmid bearing cells by immobilization. Biotechnol. Bioeng. 34: 717–724

    Google Scholar 

  • Walmsley RM, Gardner DCJ & Oliver SG (1983) Stability of a cloned gene in yeast grown in chemostat culture. Mol. Gen. Genet. 192: 361–365

    Google Scholar 

  • Wheals AE (1989) Biology of the cell cycle in yeast. In: Rose AH & Harrison JS (Eds) The Yeasts, Vol 1 (pp 283–377) Academic Press, London

    Google Scholar 

  • Wittrup KD & Bailey JE (1988) A segregated model of recombinant multicopy plasmid propagation. Biotechnol. Bioeng. 31: 304–310

    Google Scholar 

  • Zabriskie DW & Acuri EJ (1986) Factors influencing productivity of fermentation employing recombinant microorganisms. Enz. Micro. Technol. 8: 706–717

    Google Scholar 

  • Zakain VA, Brewer BJ & Fangman WL (1979) Replication of each copy of the yeast 2 micron DNA plasmid occurs during the S-phase. Cell 17: 923–934

    Google Scholar 

  • Zhu J, Contreras R & Fiers W (1986) Construction of stable laboratory and industrial yeast strains expressing a foreign gene by integrative transformation using a dominant selection system. Gene 50: 225–237

    Google Scholar 

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  1. Swiss Federal Institute for Water Resources and Water Pollution Control (EAWAG), Swiss Federal Institutes of Technology (ETH) Zürich, Ueberlandstrasse 133, CH-8600, Dübendorf, Switzerland

    C. Anthony Mason

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Mason, C.A. Physiological aspects of growth and recombinant DNA stability inSaccharomyces cerevisiae . Antonie van Leeuwenhoek 59, 269–283 (1991). https://doi.org/10.1007/BF00583680

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