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Journal of Bacteriology, August 2002, p. 4582-4593, Vol. 184, No. 16
0021-9193/02/$04.00+0     DOI: 10.1128/JB.184.16.4582-4593.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Genome-Scale Metabolic Model of Helicobacter pylori 26695

Christophe H. Schilling,1* Markus W. Covert,2 Iman Famili,2 George M. Church,3 Jeremy S. Edwards,4 and Bernhard O. Palsson2

Genomatica, Inc., San Diego, California 92121,1 Department of Bioengineering, University of California, San Diego, La Jolla, California 92093,2 Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115,3 Department of Chemical Engineering, University of Delaware, Newark, Delaware 197164

Received 17 January 2002/ Accepted 14 May 2002

A genome-scale metabolic model of Helicobacter pylori 26695 was constructed from genome sequence annotation, biochemical, and physiological data. This represents an in silico model largely derived from genomic information for an organism for which there is substantially less biochemical information available relative to previously modeled organisms such as Escherichia coli. The reconstructed metabolic network contains 388 enzymatic and transport reactions and accounts for 291 open reading frames. Within the paradigm of constraint-based modeling, extreme-pathway analysis and flux balance analysis were used to explore the metabolic capabilities of the in silico model. General network properties were analyzed and compared to similar results previously generated for Haemophilus influenzae. A minimal medium required by the model to generate required biomass constituents was calculated, indicating the requirement of eight amino acids, six of which correspond to essential human amino acids. In addition a list of potential substrates capable of fulfilling the bulk carbon requirements of H. pylori were identified. A deletion study was performed wherein reactions and associated genes in central metabolism were deleted and their effects were simulated under a variety of substrate availability conditions, yielding a number of reactions that are deemed essential. Deletion results were compared to recently published in vitro essentiality determinations for 17 genes. The in silico model accurately predicted 10 of 17 deletion cases, with partial support for additional cases. Collectively, the results presented herein suggest an effective strategy of combining in silico modeling with experimental technologies to enhance biological discovery for less characterized organisms and their genomes.

* Corresponding author. Mailing address: Genomatica, Inc., 5405 Morehouse Dr., Suite 210, San Diego, CA 92121. Phone: (858) 362-8550. Fax: (858) 824-1772. E-mail: cschilling{at}genomatica.com.

Journal of Bacteriology, August 2002, p. 4582-4593, Vol. 184, No. 16
0021-9193/02/$04.00+0     DOI: 10.1128/JB.184.16.4582-4593.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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