A model for L‐methionine production describing oxygen–productivity relationship

BACKGROUND: The state-time profile of cell mass, substrate and methionine concentrations of a methionine synthesis process shows strongly nonlinear features. A mathematical representation of this process was developed that conformed to systems analysis required for monitoring and controlling methionine production. The specific growth rate was defined by an exponential term to describe the lag phase in growth, extended before the onset of methionine production and substrate inhibition observed for this process. A switching function was used to describe the relation between methionine synthesis and dissolved oxygen concentration. In addition, the product formation kinetics of this model described the reutilization of methionine feedback regulation whenever the residual substrate concentration dropped below a critical value. RESULTS: The parameters for the model were determined from experimental data using a nonlinear regression technique. A complete nonlinear systems analysis of the model proved that using this model, the system was controllable and observable. The model prediction of methionine production in controlled and uncontrolled environments was satisfactory. Six statistical measures were employed to validate model prediction and its adequacy was shown through simulations. CONCLUSIONS: The proposed model for methionine production possesses the correct system architecture for application in process control. It predicts satisfactorily the relationship between methionine synthesis and dissolved oxygen, and time profiles of state variables. Copyright © 2008 Society of Chemical Industry

[1]  V. Uversky,et al.  Methionine oxidation inhibits fibrillation of human α‐synuclein in vitro , 2002 .

[2]  H. Pörtner,et al.  Temperature Effects on Hemocyanin Oxygen Binding in an Antarctic Cephalopod , 2001, The Biological Bulletin.

[3]  T. R. Sreekrishnan,et al.  Production of methionine by a multi-analogue resistant mutant of Corynebacterium lilium , 2003 .

[4]  K. Shimizu,et al.  Microaerobic lysine fermentations and metabolic flux analysis , 1998 .

[5]  K. Shimizu,et al.  Development of a kinetic model for L-lysine biosynthesis in Corynebacterium glutamicum and its application to metabolic control analysis. , 1999, Journal of bioscience and bioengineering.

[6]  P. Ueland,et al.  Disposition of homocysteine in subjects heterozygous for homocystinuria due to cystathionine beta-synthase deficiency: relationship between genotype and phenotype. , 2001, American journal of medical genetics.

[7]  K. Shimizu,et al.  Metabolic control analysis for lysine synthesis using Corynebacterium glutamicum and experimental verification. , 2000, Journal of bioscience and bioengineering.

[8]  C. Willmott Some Comments on the Evaluation of Model Performance , 1982 .

[9]  James Gomes,et al.  Methionine production by fermentation. , 2005, Biotechnology advances.

[10]  H. McNulty,et al.  Plasma homocysteine is not subject to seasonal variation. , 2001, Clinical chemistry.

[11]  Claudio O. Stöckle,et al.  Evaluation of estimated weather data for calculating Penman-Monteith reference crop evapotranspiration , 2004, Irrigation Science.

[12]  G. Stephanopoulos,et al.  Metabolic flux distributions in Corynebacterium glutamicum during growth and lysine overproduction , 2000, Biotechnology and bioengineering.

[13]  James Gomes,et al.  Effect of Dissolved Oxygen on Continuous Production of Methionine , 2001 .

[14]  Kartik Subramanian,et al.  Effect of cysteine on methionine production by a regulatory mutant of Corynebacterium lilium. , 2005, Bioresource technology.

[15]  M. Mackey,et al.  Modelling transcriptional feedback loops: the role of Gro/TLE1 in Hes1 oscillations , 2006, Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences.

[16]  Michael C. Mackey,et al.  Long Period Oscillations in a G0 Model of Hematopoietic Stem Cells , 2005, SIAM J. Appl. Dyn. Syst..

[17]  James Gomes,et al.  Simultaneous dissolved oxygen and glucose regulation in fed-batch methionine production using decoupled input-output linearizing control , 2009 .

[18]  Tz. Georgiev,et al.  Comparative studies of fed-batch fermentation processes for production of L-lysine and L-valine based on mathematical models , 2003, Proceedings of the 25th International Conference on Information Technology Interfaces, 2003. ITI 2003..

[19]  H. Kröger,et al.  Protection from acetaminophen-induced liver damage by the synergistic action of low doses of the poly(ADP-ribose) polymerase-inhibitor nicotinamide and the antioxidant N-acetylcysteine or the amino acid L-methionine. , 1997, General pharmacology.

[20]  Ya-Jie Tang,et al.  Modeling the kinetics of cell growth and ganoderic acid production in liquid static cultures of the medicinal mushroom , 2004 .

[21]  James Gomes,et al.  Production of l-methionine by submerged fermentation: A review , 2005 .

[22]  Moses O. Tadé,et al.  Variations and modelling of oxygen demand in amino acid production , 2001 .

[23]  Christoph Wittmann,et al.  Metabolic pathway analysis for rational design of L-methionine production by Escherichia coli and Corynebacterium glutamicum. , 2006, Metabolic engineering.

[24]  J. Ferrell Tripping the switch fantastic: how a protein kinase cascade can convert graded inputs into switch-like outputs. , 1996, Trends in biochemical sciences.

[25]  A. Stoll,et al.  S-adenosyl-l-methionine: effects on brain bioenergetic status and transverse relaxation time in healthy subjects , 2003, Biological Psychiatry.

[26]  R. Luedeking,et al.  A kinetic study of the lactic acid fermentation. Batch process at controlled pH , 2000 .

[27]  G. Stephanopoulos,et al.  Metabolic characterization of a L‐lysine‐producing strain by continuous culture , 1992, Biotechnology and bioengineering.

[28]  Xue-Wu Zhang,et al.  Time-dependent kinetic models for glutamic acid fermentation , 1998 .

[29]  K. Riet,et al.  Review of Measuring Methods and Results in Nonviscous Gas-Liquid Mass Transfer in Stirred Vessels , 1979 .

[30]  J. Gomes,et al.  Fed-batch bioproduction of spectinomycin. , 1998, Advances in biochemical engineering/biotechnology.

[31]  D. Townsend,et al.  Sulfur containing amino acids and human disease. , 2004, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[32]  O. Levenspiel The monod equation: A revisit and a generalization to product inhibition situations , 1980 .

[33]  H. C. Lim,et al.  Kinetics of l-lysine fermentation: a continuous culture model incorporating oxygen uptake rate , 2003, Applied Microbiology and Biotechnology.

[34]  J. Monod The Growth of Bacterial Cultures , 1949 .