A systematic approach for finding the objective function and active constraints for dynamic flux balance analysis

• Published in: Bioprocess and biosystems engineering Vol. 41; no. 5; pp. 641 - 655
• Main Authors: Nikdel, Ali, Braatz, Richard D., Budman, Hector M.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.05.2018; Springer Nature B.V
• Subjects: algorithms; batch fermentation; Biomass; Biotechnology; Bordetella pertussis; Chemical engineering; Chemistry; Chemistry and Materials Science; Computer simulation; Constraint modelling; data collection; E coli; Environmental Engineering/Biotechnology; Enzymes; Escherichia coli; Experimental data; Fermentation; Food Science; Industrial and Production Engineering; Industrial Chemistry/Chemical Engineering; Mathematical models; Metabolism; Metabolites; Model matching; Objective function; Optimization; Pertussis; Research Paper; whooping cough; Metabolic engineering; Flux balance analysis; Bioprocess modeling; Dynamic flux balance analysis; Metabolic networks
• ISSN: 1615-7591; 1615-7605; 1615-7605
• DOI: 10.1007/s00449-018-1899-y

Dynamic flux balance analysis (DFBA) has become an instrumental modeling tool for describing the dynamic behavior of bioprocesses. DFBA involves the maximization of a biologically meaningful objective subject to kinetic constraints on the rate of consumption/production of metabolites. In this paper, we propose a systematic data-based approach for finding both the biological objective function and a minimum set of active constraints necessary for matching the model predictions to the experimental data. The proposed algorithm accounts for the errors in the experiments and eliminates the need for ad hoc choices of objective function and constraints as done in previous studies. The method is illustrated for two cases: (1) for in silico (simulated) data generated by a mathematical model for Escherichia coli and (2) for actual experimental data collected from the batch fermentation of Bordetella Pertussis (whooping cough).