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Interrogating <jats:italic>C. beijerinckii<\/jats:italic> metabolism from a systems viewpoint using constraint-based modeling allows for simulation of the global effect of genetic modifications.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>We present the first genome-scale metabolic model (<jats:italic>i<\/jats:italic> CM925) for <jats:italic>C. beijerinckii<\/jats:italic>, containing 925 genes, 938 reactions, and 881 metabolites. To build the model we employed a semi-automated procedure that integrated genome annotation information from KEGG, BioCyc, and The SEED, and utilized computational algorithms with manual curation to improve model completeness. Interestingly, we found only a 34% overlap in reactions collected from the three databases--highlighting the importance of evaluating the predictive accuracy of the resulting genome-scale model. To validate <jats:italic>i<\/jats:italic> CM925, we conducted fermentation experiments using the NCIMB 8052 strain, and evaluated the ability of the model to simulate measured substrate uptake and product production rates. Experimentally observed fermentation profiles were found to lie within the solution space of the model; however, under an optimal growth objective, additional constraints were needed to reproduce the observed profiles--suggesting the existence of selective pressures other than optimal growth. Notably, a significantly enriched fraction of actively utilized reactions in simulations--constrained to reflect experimental rates--originated from the set of reactions that overlapped between all three databases (<jats:italic>P<\/jats:italic> = 3.52 \u00d7 10<jats:sup>-9<\/jats:sup>, Fisher's exact test). Inhibition of the hydrogenase reaction was found to have a strong effect on butanol formation--as experimentally observed.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Microbial production of butanol by <jats:italic>C. beijerinckii<\/jats:italic> offers a promising, sustainable, method for generation of this important chemical and potential biofuel. <jats:italic>i<\/jats:italic> CM925 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 improved butanol production.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1752-0509-5-130","type":"journal-article","created":{"date-parts":[[2011,8,17]],"date-time":"2011-08-17T06:14:04Z","timestamp":1313561644000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":90,"title":["Metabolic network reconstruction and genome-scale model of butanol-producing strain Clostridium beijerinckii NCIMB 8052"],"prefix":"10.1186","volume":"5","author":[{"given":"Caroline B","family":"Milne","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James A","family":"Eddy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ravali","family":"Raju","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soroush","family":"Ardekani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pan-Jun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan S","family":"Senger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong-Su","family":"Jin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans P","family":"Blaschek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathan D","family":"Price","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2011,8,16]]},"reference":[{"key":"738_CR1","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1002\/bit.22003","volume":"101","author":"SY Lee","year":"2008","unstructured":"Lee SY, Park JH, Jang SH, Nielsen LK, Kim J, Jung KS: Fermentative butanol production by Clostridia. 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