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PMID: 18767192 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Genome-scale model for Clostridium acetobutylicum: Part I. Metabolic network resolution and analysis.

Biotechnology and bioengineering ·Vol. 101 ·No. 5 ·2008-12-01 ·Pages 1036-52

Senger RS, Papoutsakis ET

Abstract

A genome-scale metabolic network reconstruction for Clostridium acetobutylicum (ATCC 824) was carried out using a new semi-automated reverse engineering algorithm. The network consists of 422 intracellular metabolites involved in 552 reactions and includes 80 membrane transport reactions. The metabolic network illustrates the reliance of clostridia on the urea cycle, intracellular L-glutamate solute pools, and the acetylornithine transaminase for amino acid biosynthesis from the 2-oxoglutarate precursor. The semi-automated reverse engineering algorithm identified discrepancies in reaction network databases that are major obstacles for fully automated network-building algorithms. The proposed semi-automated approach allowed for the conservation of unique clostridial metabolic pathways, such as an incomplete TCA cycle. A thermodynamic analysis was used to determine the physiological conditions under which proposed pathways (e.g., reverse partial TCA cycle and reverse arginine biosynthesis pathway) are feasible. The reconstructed metabolic network was used to create a genome-scale model that correctly characterized the butyrate kinase knock-out and the asolventogenic M5 pSOL1 megaplasmid degenerate strains. Systematic gene knock-out simulations were performed to identify a set of genes encoding clostridial enzymes essential for growth in silico.

MeSH Terms
Arginine/biosynthesis Cell Growth Processes/genetics Clostridium acetobutylicum/genetics,growth & development,metabolism Computational Biology/methods Gene Knockout Techniques Genome, Bacterial/physiology Glutamic Acid/analysis,metabolism Kinetics Metabolic Networks and Pathways/genetics Models, Biological Ornithine/biosynthesis Phosphotransferases (Carboxyl Group Acceptor)/genetics,metabolism Thermodynamics Transaminases/analysis,metabolism Urea/metabolism
Chemicals
Glutamic Acid Urea Arginine Ornithine Transaminases acetylornithine transaminase Phosphotransferases (Carboxyl Group Acceptor) butyrate kinase
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Senger Ryan S
Delaware Biotechnology Institute, University of Delaware, 15 Innovation Way Newark, Delaware 19711, USA. [email protected]
Papoutsakis Eleftherios T
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Article Info
Journal
Biotechnology and bioengineering
Abbr.
Biotechnol Bioeng
ISSN
1097-0290
DOI
10.1002/bit.22010
Email
[email protected]
Published
2008-12-01
Pages
1036-52
Language
English
Region
United States
NLM ID
7502021
PMCID
PMC2760220
Subset
IM
Grants
NIGMS NIH HHS · F32 GM078947-02 · United States
NIGMS NIH HHS · F32 GM078947-03 · United States
NIGMS NIH HHS · F32 GM078947-01A1 · United States
NIGMS NIH HHS · F32GM078947 · United States
NIGMS NIH HHS · F32 GM078947 · United States
External Links
PubMed source DOI: 10.1002/bit.22010 PMC Full Text View journal details
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