A novel process-based model of microbial growth: self-inhibition in Saccharomyces cerevisiae aerobic fed-batch cultures

Microbial Cell Factories - Tập 14 - Trang 1-14 - 2015
Stefano Mazzoleni1, Carmine Landi2, Fabrizio Cartenì1, Elisabetta de Alteriis3, Francesco Giannino1, Lucia Paciello2, Palma Parascandola2
1Dept. di Agraria, Università degli Studi di Napoli Federico II, Portici, Italy
2Dept. di Ingegneria Industriale, Università degli Studi di Salerno, Fisciano, Italy
3Dept. di Biologia, Università degli Studi di Napoli Federico II, Naples, Italy

Tóm tắt

Microbial population dynamics in bioreactors depend on both nutrients availability and changes in the growth environment. Research is still ongoing on the optimization of bioreactor yields focusing on the increase of the maximum achievable cell density. A new process-based model is proposed to describe the aerobic growth of Saccharomyces cerevisiae cultured on glucose as carbon and energy source. The model considers the main metabolic routes of glucose assimilation (fermentation to ethanol and respiration) and the occurrence of inhibition due to the accumulation of both ethanol and other self-produced toxic compounds in the medium. Model simulations reproduced data from classic and new experiments of yeast growth in batch and fed-batch cultures. Model and experimental results showed that the growth decline observed in prolonged fed-batch cultures had to be ascribed to self-produced inhibitory compounds other than ethanol. The presented results clarify the dynamics of microbial growth under different feeding conditions and highlight the relevance of the negative feedback by self-produced inhibitory compounds on the maximum cell densities achieved in a bioreactor.

Tài liệu tham khảo

Buchanan R (1918) Life phases in a bacterial culture. J Infect Dis 23:109–125 Monod J (1949) The growth of bacterial cultures. Annu Rev Microbiol 3:371–394 Bailey JE, Ollis F (1986) Biochemical engineering fundamentals. Mc-Graw-Hill, New York Botstein D, Fink GR (2011) Yeast: an experimental organism for 21st Century biology. Genetics 189:695–704 Nevoigt E (2008) Progress in metabolic engineering of Saccharomyces cerevisiae. Microbiol Mol Biol Rev 72:379–412 Porro D, Gasser B, Fossati T, Maurer M, Branduardi P, Sauer M et al (2011) Production of recombinant proteins and metabolites in yeasts: when are these systems better than bacterial production systems? Appl Microbiol Biotechnol 89:939–948 Hong KK, Nielsen J (2012) Metabolic engineering of Saccharomyces cerevisiae: a key cell factory platform for future biorefineries. Cell Mol Life Sci 69:2671–2690 Fiechter A, Seghezzi W (1992) Regulation of glucose metabolism in growing yeast cells. J Biotechnol 27:27–45 De Deken RH (1966) The Crabtree effect: a regulatory system in yeast. J Gen Microbiol 44:149–156 Holzer H (1976) Catabolite inactivation in yeast. Trends Biochem Sci 1:178–181 Sonnleitner B, Käppeli O (1986) Growth of Saccharomyces cerevisiae is controlled by its limited respiratory capacity: formulation and verification of a hypothesis. Biotechnol Bioeng 28:927–937 Pham HT, Larsson G, Enfors SO (1998) Growth and energy metabolism in aerobic fed-batch cultures of Saccharomyces cerevisiae: simulation and model verification. Biotechnol Bioeng 60:474–482 Sonnleitner B, Hahnemann U (1994) Dynamics of the respiratory bottleneck of Saccharomyces cerevisiae. J Biotechnol 38:63–79 Magasanik B (1961) Catabolite repression. Cold Spring Harb Symp Quant Biol 26:249–256 Gancedo JM (1998) Yeast carbon catabolite repression. Microbiol Mol Biol Rev 62:334–361 Westergaard SL, Oliveira AP, Bro C, Olsson L, Nielsen J (2007) A systems biology approach to study glucose repression in the yeast Saccharomyces cerevisiae. Biotechnol Bioeng 96:134–145 Pirt SJ (1975) Principles of microbe and cell cultivation. Blackwell Scientific Publications Ltd., Oxford Reed G, Peppler H (1973) Baker’s yeast production. In: Reed G, Peppler H (eds) Yeast technology. Avi Publishing Comp., Westport, pp 53–102 Porro D, Sauer M, Branduardi P, Mattanovich D (2005) Recombinant protein production in yeasts. Mol Biotechnol 31:245–259 Riesenberg D, Guthke R (1999) High-cell-density cultivation of microorganisms. Appl Microbiol Biotechnol 51:422–430 Riesenberg D (1991) High-cell-density cultivation of Escherichia coli. Curr Opin Biotechnol 2:380–384 Lee SY (1996) High cell-density culture of Escherichia coli. Trends Biotechnol 14:604–611 Shiloach J, Fass R (2005) Growing E. coli to high cell density—a historical perspective on method development. Biotechnol Adv 23:345–357 Van Hoek P, De Hulster E, Van Dijken JP, Pronk JT (2000) Fermentative capacity in high-cell-density fed-batch cultures of baker’s yeast. Biotechnol Bioeng 68:517–523 Fu Z, Verderame TD, Leighton JM, Sampey BP, Appelbaum ER, Patel PS et al (2014) Exometabolome analysis reveals hypoxia at the up-scaling of a Saccharomyces cerevisiae high-cell density fed-batch biopharmaceutical process. Microb Cell Fact 13:32 Mattanovich D, Gasser B, Hohenblum H, Sauer M (2004) Stress in recombinant protein producing yeasts. J Biotechnol 113:121–135 Landi C, Paciello L, de Alteriis E, Brambilla L, Parascandola P (2011) Effect of auxotrophies on yeast performance in aerated fed-batch reactor. Biochem Biophys Res Commun 414:604–611 Landi C, Paciello L, de Alteriis E, Brambilla L, Parascandola P (2015) High cell density culture with S. cerevisiae CEN.PK113-5D for IL-1β production: optimization, modeling, and physiological aspects. Bioprocess Biosyst Eng 38:251–261 Paciello L, de Alteriis E, Mazzoni C, Palermo V, Zueco J, Parascandola P (2009) Performance of the auxotrophic Saccharomyces cerevisiae BY4741 as host for the production of IL-1beta in aerated fed-batch reactor: role of ACA supplementation, strain viability, and maintenance energy. Microb Cell Fact 8:70 Verhulst PF (1838) Notice sur la loi que la population suit dans son accroissement. Corresp Math Phys 10:113–129 Jannasch HW, Egli T (1993) Microbial growth kinetics: a historical perspective. Antonie Van Leeuwenhoek 63:213–224 Contois DE (1959) Kinetics of bacterial growth: relationship between population density and specific growth rate of continuous cultures. J Gen Microbiol 21:40–50 Ierusalimsky ND, Neronova NM (1965) Quantitative relationship between metabolic products concentration and growth rate of microrganisms. Ann USSR Acad Sci 161:1437–1440 Barford JP, Hall RJ (1981) A mathematical model for the aerobic growth of Saccharomyces cerevisiae with a saturated respiratory capacity. Biotechnol Bioeng 23:1735–1762 Coppella SJ, Dhurjati P (1990) A mathematical description of recombinant yeast. Biotechnol Bioeng 35:356–374 Lei F, Rotbøll M, Jørgensen SB (2001) A biochemically structured model for Saccharomyces cerevisiae. J Biotechnol 88:205–221 Hanegraaf PPF, Stouthamer AH, Kooijman SALM (2000) A mathematical model for yeast respiro-fermentative physiology. Yeast 16:423–437 Ramkrishna D (1983) Foundations of biochemical engineering. In: Blanch HW, Papoutsakis ET, Stephanopoulos G (eds) Foundations of biochemical engineering, (ACS Symposium Series), vol 207., American Chemical SocietyWashington, D.C., pp 161–178 Jones KD, Kompala DS (1999) Cybernetic model of the growth dynamics of Saccharomyces cerevisiae in batch and continuous cultures. J Biotechnol 71:105–131 Giuseppin ML, van Riel NA (2000) Metabolic modeling of Saccharomyces cerevisiae using the optimal control of homeostasis: a cybernetic model definition. Metab Eng 2:14–33 Di Serio M, Aramo P, de Alteriis E, Tesser R, Santacesaria E (2003) Quantitative analysis of the key factors affecting yeast growth. Ind Eng Chem Res 42:5109–5116 Förster J, Famili I, Fu P, Palsson BØ, Nielsen J (2003) Genome-scale reconstruction of the Saccharomyces cerevisiae metabolic network. Genome Res 13:244–253 Castrillo JI, Zeef LA, Hoyle DC, Zhang N, Hayes A, Gardner DCJ et al (2007) Growth control of the eukaryote cell: a systems biology study in yeast. J Biol 6:4 Adiamah DA, Handl J, Schwartz J-M (2010) Streamlining the construction of large-scale dynamic models using generic kinetic equations. Bioinformatics 26:1324–1331 Forrester JW (1961) Industrial dynamics, vol 2. MIT press, Cambridge Bonanomi G, Giannino F, Mazzoleni S (2005) Negative plant-soil feedback and species coexistence. Oikos 111:311–321 Mazzoleni S, Bonanomi G, Giannino F, Incerti G, Dekker SC, Rietkerk M (2010) Modelling the effects of litter decomposition on tree diversity patterns. Ecol Model 221:2784–2792 Carteni F, Marasco A, Bonanomi G, Mazzoleni S, Rietkerk M, Giannino F (2012) Negative plant soil feedback explaining ring formation in clonal plants. J Theor Biol 313:153–161 Stanley D, Bandara A, Fraser S, Chambers PJ, Stanley GA (2010) The ethanol stress response and ethanol tolerance of Saccharomyces cerevisiae. J Appl Microbiol 109:13–24 Wilson WA, Roach PJ, Montero M, Baroja-Fernández E, Muñoz FJ, Eydallin G et al (2010) Regulation of glycogen metabolism in yeast and bacteria. FEMS Microbiol Rev 34:952–985 Granot D, Levine A, Dorhefetz E (2003) Sugar-induced apoptosis in yeast cells. FEMS Yeast Res 4:7–13 Granot D, Dai N (1997) Sugar induced cell death in yeast is dependent on the rate of sugar phosphorylation as determined by Arabidopsis thaliana hexokinase. Cell Death Differ 4:555–559 Von Meyenburg HK (1969) Energetics of the budding cycle of Saccharomyces cerevisiae during glucose limited aerobic growth. Arch Mikrobiol 66:289–303 Heyland J, Fu J, Blank LM (2009) Correlation between TCA cycle flux and glucose uptake rate during respiro-fermentative growth of Saccharomyces cerevisiae. Microbiology 155:3827–3837 Weusthuis RA, Pronk JT, van den Broek PJ, van Dijken JP (1994) Chemostat cultivation as a tool for studies on sugar transport in yeasts. Microbiol Rev 58:616–630 Christen S, Sauer U (2011) Intracellular characterization of aerobic glucose metabolism in seven yeast species by 13C flux analysis and metabolomics. FEMS Yeast Res 11:263–272 Van Urk H, Schipper D, Breedveld GJ, Mak PR, Scheffers WA, van Dijken JP (1989) Localization and kinetics of pyruvate-metabolizing enzymes in relation to aerobic alcoholic fermentation in Saccharomyces cerevisiae CBS 8066 and Candida utilis CBS 621. Biochim Biophys Acta 992:78–86 Kresze GB, Ronft H (1981) Pyruvate dehydrogenase complex from baker’s yeast. 1. Purification and some kinetic and regulatory properties. Eur J Biochem 119:573–579 Postma E, Verduyn C, Scheffers WA, Van Dijken JP (1989) Enzymic analysis of the crabtree effect in glucose-limited chemostat cultures of Saccharomyces cerevisiae. Appl Environ Microbiol 55:468–477 Paciello L, Zueco J, Landi C (2014) On the fermentative behavior of auxotrophic strains of Saccharomyces cerevisiae. Electron J Biotechnol 17:246–249 Van Maris AJA, Geertman JMA, Vermeulen A, Groothuizen MK, Winkler AA, Piper MDW et al (2004) Directed evolution of pyruvate decarboxylase-negative Saccharomyces cerevisiae, yielding a C2-Independent, glucose-tolerant, and pyruvate-hyperproducing yeast. Appl Environ Microbiol 70:159–166 Paalme T, Elken R, Vilu R, Korhola M (1997) Growth efficiency of Saccharomyces cerevisiae on glucose/ethanol media with a smooth change in the dilution rate (A-stat). Enzyme Microb Technol 20:174–181 Polakis ES, Bartley W (1966) Changes in dry weight, protein, deoxyribonucleic acid, ribonucleic acid and reserve and structural carbohydrate during the aerobic growth cycle of yeast. Biochem J 98:883–887 Yang K-M, Lee N-R, Woo J-M, Choi W, Zimmermann M, Blank LM et al (2012) Ethanol reduces mitochondrial membrane integrity and thereby impacts carbon metabolism of Saccharomyces cerevisiae. FEMS Yeast Res 12:675–684 Walker GM (1998) Yeast growth. In: Walker GM (ed) Yeast physiology and biotechnology. John Wiley and Sons Ltd, New York, pp 101–183 Haddad SA, Lindegren CC (1953) A method for determining the weight of an individual yeast cell. Appl Microbiol 1:153–156 Yang YT, Bennett GN, San KY (2001) The effects of feed and intracellular pyruvate levels on the redistribution of metabolic fluxes in Escherichia coli. Metab Eng 3:115–123 Diderich JA, Raamsdonk LM, Kruckeberg AL, Berden JA, Van Dam K (2001) Physiological properties of Saccharomyces cerevisiae from which hexokinase II has been deleted. Appl Environ Microbiol 67:1587–1593 Van Dijken J, Bauer J, Brambilla L, Duboc P, Francois J, Gancedo C et al (2000) An interlaboratory comparison of physiological and genetic properties of four Saccharomyces cerevisiae strains. Enzyme Microb Technol 26:706–714 Pronk J, Steensma H, Van Dijken J (1996) Pyruvate metabolism in Saccharomyces cerevisiae. Yeast 12:1607–1633 Alberghina L, Mavelli G, Drovandi G, Palumbo P, Pessina S, Tripodi F et al (2012) Cell growth and cell cycle in Saccharomyces cerevisiae: basic regulatory design and protein-protein interaction network. Biotechnol Adv 30:52–72 Youk H, van Oudenaarden A (2009) Growth landscape formed by perception and import of glucose in yeast. Nature 462:875–879 Yu T, Sheu S-S, Robotham JL, Yoon Y (2008) Mitochondrial fission mediates high glucose-induced cell death through elevated production of reactive oxygen species. Cardiovasc Res 79:341–351 MacFarlane M, Robinson G, Cain K (2012) Glucose—a sweet way to die. Cell Cycle 11:3919–3925 Gancedo C, Serrano R (1989) Energy-yielding metabolism. In: Rose AH, Harrison JS (eds) The yeasts, vol 3. Academic Press, Ltd., London, pp 205–259 Enfors SO, Häggström L (1998) Bioprocess technology: fundamentals and applications. Royal Institute of Technology, Stockholm Rahn O (1932) Physiology of bacteria. P. Blakiston’s Son & Co, Philadelphia Panikov NS (1995) Microbial growth kinetics. Chapman & Hall, London Paciello L, Landi C, Zueco J, Parascandola P (2013) Production in fed-batch reactor of Bacillus subtilis LipaseA immobilized on its own producer Saccharomyces cerevisiae cells. Chem Eng Trans 32:907–912 Casatta N, Porro A, Orlandi I, Brambilla L, Vai M (2013) Acetate but not propionate induces oxidative stress in bakers’ yeast Saccharomyces cerevisiae. Biochim Biophys Acta 1833:593–601 Semchyshyn HM, Abrat OB, Miedzobrodzki J, Inoue Y, Lushchak VI (2011) Acetate but not propionate induces oxidative stress in bakers’ yeast Saccharomyces cerevisiae. Redox Rep 16:15–23 Galdieri L, Mehrotra S, Yu S, Vancura A (2010) Transcriptional regulation in yeast during diauxic shift and stationary phase. Omics J Integr Biol 14:629–638 Shampine LF, Reichelt MW (1997) The MATLAB ODE suite. SIAM J Sci Comput 18:1–22 Lagarias JC, Reeds JA, Wright MH, Wright PE (1998) Convergence properties of the Nelder–Mead simplex method in low dimensions. SIAM J Optim 9:112–147 Nijkamp JF, van den Broek M, Datema E, de Kok S, Bosman L, Luttik MA et al (2012) De novo sequencing, assembly and analysis of the genome of the laboratory strain Saccharomyces cerevisiae CEN.PK113-7D, a model for modern industrial biotechnology. Microb Cell Fact 11:36 Verduyn C, Postma E, Scheffers W, Van Dijken J (1992) Effect of benzoic acid on metabolic fluxes in yeasts: a continuous-culture study on the regulation of respiration and alcoholic fermentation. Yeast 8:501–517 Pronk JT (2002) Auxotrophic yeast strains in fundamental and applied research. Appl Environ Microbiol 68:2095–2100