Stoichiometric modeling of Clostridium acetobutylicum fermentations with non-linear constraints.
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.
Desai
R P
RP
Department of Chemical Engineering, Northwestern University, Evanston, IL 60208, USA.
Nielsen
L K
LK
Papoutsakis
E T
ET
D000085:Acetates / Q000378:metabolism; D002087:Butyrates / Q000378:metabolism; D003013:Clostridium / Q000378:metabolism*; D005285:Fermentation; D008954:Models, Biological
D000085:Acetates; D002087:Butyrates