Title
Genome-scale metabolic analysis of Clostridium thermocellum for bioethanol production.
Abstract
BACKGROUND: Microorganisms possess diverse metabolic capabilities that can potentially be leveraged for efficient production of biofuels. Clostridium thermocellum (ATCC 27405) is a thermophilic anaerobe that is both cellulolytic and ethanologenic, meaning that it can directly use the plant sugar, cellulose, and biochemically convert it to ethanol. A major challenge in using microorganisms for chemical production is the need to modify the organism to increase production efficiency. The process of properly engineering an organism is typically arduous. RESULTS: Here we present a genome-scale model of C. thermocellum metabolism, iSR432, for the purpose of establishing a computational tool to study the metabolic network of C. thermocellum and facilitate efforts to engineer C. thermocellum for biofuel production. The model consists of 577 reactions involving 525 intracellular metabolites, 432 genes, and a proteomic-based representation of a cellulosome. The process of constructing this metabolic model led to suggested annotation refinements for 27 genes and identification of areas of metabolism requiring further study. The accuracy of the iSR432 model was tested using experimental growth and by-product secretion data for growth on cellobiose and fructose. Analysis using this model captures the relationship between the reduction-oxidation state of the cell and ethanol secretion and allowed for prediction of gene deletions and environmental conditions that would increase ethanol production. CONCLUSIONS: By incorporating genomic sequence data, network topology, and experimental measurements of enzyme activities and metabolite fluxes, we have generated a model that is reasonably accurate at predicting the cellular phenotype of C. thermocellum and establish a strong foundation for rational strain design. In addition, we are able to draw some important conclusions regarding the underlying metabolic mechanisms for observed behaviors of C. thermocellum and highlight remaining gaps in the existing genome annotations.
Year
DOI
Venue
2010
10.1186/1752-0509-4-31
BMC systems biology
Keywords
Field
DocType
bioinformatics,bioenergy,network topology,ethanol production,genome annotation,production efficiency,metabolic network,genomes,genomics,algorithms,biofuels,systems biology,enzyme activity,genome sequence
Biology,Systems biology,Thermophile,Bioinformatics,Clostridium thermocellum,Biofuel,Microorganism,Flux balance analysis,Cellobiose,Organism
Journal
Volume
Issue
ISSN
4
1
1752-0509
Citations 
PageRank 
References 
18
0.61
7
Authors
4
Name
Order
Citations
PageRank
Seth B. Roberts1311.92
Chris M. Gowen2281.59
J. Paul Brooks3899.31
Stephen S. Fong4454.29