Metabolic network reconstruction and genome-scale model of butanol-producing strain Clostridium beijerinckii NCIMB 8052

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dc.contributor.authorMilne, Caroline B.en
dc.contributor.authorEddy, James A.en
dc.contributor.authorRaju, Ravalien
dc.contributor.authorArdekani, Soroushen
dc.contributor.authorKim, Pan-Junen
dc.contributor.authorSenger, Ryan S.en
dc.contributor.authorJin, Yong-Suen
dc.contributor.authorBlaschek, Hans P.en
dc.contributor.authorPrice, Nathan D.en
dc.contributor.departmentBiological Systems Engineeringen
dc.date.accessioned2012-08-24T11:01:09Zen
dc.date.available2012-08-24T11:01:09Zen
dc.date.issued2011-08-16en
dc.date.updated2012-08-24T11:01:09Zen
dc.description.abstractBackground Solventogenic clostridia offer a sustainable alternative to petroleum-based production of butanol--an important chemical feedstock and potential fuel additive or replacement. C. beijerinckii is an attractive microorganism for strain design to improve butanol production because it (i) naturally produces the highest recorded butanol concentrations as a byproduct of fermentation; and (ii) can co-ferment pentose and hexose sugars (the primary products from lignocellulosic hydrolysis). Interrogating C. beijerinckii metabolism from a systems viewpoint using constraint-based modeling allows for simulation of the global effect of genetic modifications. Results We present the first genome-scale metabolic model (iCM925) for C. beijerinckii, 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 iCM925, 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 (P = 3.52 x 10-9, Fisher's exact test). Inhibition of the hydrogenase reaction was found to have a strong effect on butanol formation--as experimentally observed. Conclusions Microbial production of butanol by C. beijerinckii offers a promising, sustainable, method for generation of this important chemical and potential biofuel. iCM925 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.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationBMC Systems Biology. 2011 Aug 16;5(1):130en
dc.identifier.doihttps://doi.org/10.1186/1752-0509-5-130en
dc.identifier.urihttp://hdl.handle.net/10919/18798en
dc.language.isoenen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.holderCaroline B Milne et al.; licensee BioMed Central Ltd.en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleMetabolic network reconstruction and genome-scale model of butanol-producing strain Clostridium beijerinckii NCIMB 8052en
dc.title.serialBMC Systems Biologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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