S140: "Metabolic reconstruction and genome-scale model of butanol producing organism Clostridium beijerinckii NCIMB 8052"

Solventogenic clostridia offer a sustainable alternative to petroleum-based production of butanol—an important chemical and potential transportation fuel.  Clostridium beijerinckii is an attractive candidate for strain design to improve butanol production because it naturally produces the highest recorded butanol concentrations and can co-ferment pentose and hexose sugars (the primary products from lignocellulosic hydrolysis).  Interrogating its metabolism using constraint-based modeling allows for simulation of the global effect of genetic modifications.  We present the first genome-scale metabolic model for C. beijerinckii, containing 925 genes, 938 reactions, and 881 metabolites.  We built the model using a semi-automated procedure that integrated genome annotation information from KEGG, BioCyc, and The SEED, and utilized computational algorithms and manual curation to improve model completeness.  To validate the iCM925 model we conducted fermentation experiments using the NCIMB 8052 strain, and evaluated the ability of the model to simulate substrate uptake and product production rates.  Our findings show that the iCM925 model is a predictive model that can accurately reproduce physiological behavior and provide insight into the underlying mechanisms of microbial butanol production. As such, the model will be instrumental in efforts to better understand, and metabolically engineer, this microorganism for sustainable butanol production.