title: Stoichiometric modeling of Clostridium acetobutylicum fermentations with non-linear constraints.
abstract: A stoichiometric model of Clostridium acetobutylicum and related strains has been previously derived. The stoichiometric matrix of the model contains a singularity which has prevented the calculation of a unique set of fluxes which describe the primary metabolic activity. To resolve the singularity, we have developed a non-linear constraint relating the acetate and butyrate uptake fluxes. Subsequently, we developed a software package utilizing a model independent heuristic global optimization approach to solve the resultant non-linear problem. We have validated the use of the non-linear constraint by correlating calculated butyrate production pathway flux profiles with measured intracellular pH profiles. Finally, we examined a controlled batch fermentation to determine that the acid formation pathways play critical roles throughout solventogenesis. The broader usefulness of reformulating the stoichiometric model as a constrained minimization problem is discussed.
authors.affiliation: Department of Chemical Engineering, Northwestern University, Evanston, IL 60208, USA.
authors.forename: R P
authors.initials: RP
authors.lastname: Desai
authors.forename: L K
authors.initials: LK
authors.lastname: Nielsen
authors.forename: E T
authors.initials: ET
authors.lastname: Papoutsakis
mesh_terms: D000085:Acetates / Q000378:metabolism; D002087:Butyrates / Q000378:metabolism; D003013:Clostridium / Q000378:metabolism*; D005285:Fermentation; D008954:Models, Biological
chemical_list: D000085:Acetates; D002087:Butyrates