Dynamic Metabolic Modeling of Denitrifying Bacterial Growth: The Cybernetic Approach

Denitrification is a multistage reduction process converting nitrate ultimately to nitrogen gas, carried out mostly by facultative bacteria. Modeling of the denitrification process is challenging due to the complex metabolic regulation that modulates sequential formation and consumption of a series of nitrogen oxide intermediates, which serve as the final electron acceptors for denitrifying bacteria. In this work, we examined the effectiveness and accuracy of the cybernetic modeling framework in simulating the growth dynamics of denitrifying bacteria in comparison with kinetic models. In four different case studies using the literature data, we successfully simulated diauxic and triauxic growth patterns observed in anoxic and aerobic conditions, only by tuning two or three parameters. In order to understand the regulatory structure of the cybernetic model, we systematically analyzed the effect of cybernetic control variables on simulation accuracy. The results showed that the consideration of both enzyme ...

[1]  Doraiswami Ramkrishna,et al.  Prediction of metabolic function from limited data: Lumped hybrid cybernetic modeling (L‐HCM) , 2010, Biotechnology and bioengineering.

[2]  D. Ramkrishna,et al.  Cybernetic modeling of bacterial cultures at low growth rates: Mixed‐substrate systems , 1988, Biotechnology and bioengineering.

[3]  Jamey D. Young,et al.  Integrating cybernetic modeling with pathway analysis provides a dynamic, systems‐level description of metabolic control , 2008, Biotechnology and bioengineering.

[4]  Michael Kornaros,et al.  Kinetic modelling of Pseudomonas denitrificans growth and denitrification under aerobic, anoxic and transient operating conditions , 1998 .

[5]  A. Konopka,et al.  Mathematical Modeling of Microbial Community Dynamics: A Methodological Review , 2014 .

[6]  G. T. Tsao,et al.  Investigation of bacterial growth on mixed substrates: Experimental evaluation of cybernetic models , 1986, Biotechnology and bioengineering.

[7]  D. Ramkrishna,et al.  A hybrid model of anaerobic E. coli GJT001: Combination of elementary flux modes and cybernetic variables , 2008, Biotechnology progress.

[8]  D. Ramkrishna,et al.  Metabolic regulation in bacterial continuous cultures: I , 1991, Biotechnology and bioengineering.

[9]  Doraiswami Ramkrishna,et al.  Dynamic modeling of aerobic growth of Shewanella oneidensis. Predicting triauxic growth, flux distributions, and energy requirement for growth. , 2013, Metabolic engineering.

[10]  Doraiswami Ramkrishna,et al.  Dynamic analysis of the cybernetic model for diauxic growth , 1997 .

[11]  A. Kienle,et al.  Experimental and theoretical analysis of poly (β-hydroxybutyrate) formation and consumption in Ralstonia eutropha , 2011 .

[12]  D. Ramkrishna,et al.  Metabolic engineering from a cybernetic perspective: aspartate family of amino acids. , 1999, Metabolic engineering.

[14]  Doraiswami Ramkrishna,et al.  On the Matching and Proportional Laws of Cybernetic Models , 2007, Biotechnology progress.

[15]  Doraiswami Ramkrishna,et al.  Prediction of dynamic behavior of mutant strains from limited wild-type data. , 2012, Metabolic engineering.

[16]  G. T. Tsao,et al.  Cybernetic modeling of microbial growth on multiple substrates , 1984, Biotechnology and bioengineering.

[17]  D. Ramkrishna,et al.  Modeling metabolic systems: the need for dynamics , 2013 .

[18]  D. Ramkrishna,et al.  Prediction of dynamic metabolic behavior of Pediococcus pentosaceus producing lactic acid from lignocellulosic sugars , 2012, Biotechnology progress.

[19]  Doraiswami Ramkrishna,et al.  Cybernetic Modeling and Regulation of Metabolic Pathways. Growth on Complementary Nutrients , 1994 .

[20]  D. Reed,et al.  Gene-centric approach to integrating environmental genomics and biogeochemical models , 2014, Proceedings of the National Academy of Sciences.

[21]  D. Ramkrishna.  A Cybernetic Perspective of Microbial Growth , 1983 .

[22]  J. Varner,et al.  Large-scale prediction of phenotype: concept. , 2000, Biotechnology and bioengineering.

[23]  Matthias Reuss,et al.  Optimal Experimental Design for Parameter Estimation in Unstructured Growth Models , 1994 .

[24]  G. T. Tsao,et al.  A cybernetic view of microbial growth: Modeling of cells as optimal strategists , 1985, Biotechnology and bioengineering.

[25]  S. Pavlou,et al.  A kinetic study of hydrogenotrophic denitrification , 2006 .

[26]  Doraiswami Ramkrishna,et al.  Exacting predictions by cybernetic model confirmed experimentally: Steady state multiplicity in the chemostat , 2012, Biotechnology progress.

[27]  K. Bourtzis,et al.  Kinetics of pure cultures of hydrogen‐oxidizing denitrifying bacteria and modeling of the interactions among them in mixed cultures , 2006, Biotechnology and bioengineering.

[28]  D. Ramkrishna,et al.  Systematic development of hybrid cybernetic models: Application to recombinant yeast co‐consuming glucose and xylose , 2009, Biotechnology and bioengineering.

[29]  Doraiswami Ramkrishna,et al.  Dynamic models of metabolism: Review of the cybernetic approach , 2012 .

[30]  Jingqi Yuan,et al.  On enhancing productivity of bioethanol with multiple species , 2012, Biotechnology and bioengineering.

[31]  D. Ramkrishna,et al.  Cybernetic models based on lumped elementary modes accurately predict strain‐specific metabolic function , 2011, Biotechnology and bioengineering.

[32]  Abhijit Anand Namjoshi,et al.  Multiplicity and stability of steady states in continuous bioreactors: dissection of cybernetic models , 2001 .